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Study of Bevacizumab + mFOLFOX6 Versus Bevacizumab + FOLFIRI With Biomarker Stratification in Participants With Previously Untreated Metastatic Colorectal Cancer (mCRC) (MAVERICC)

30. juni 2016 oppdatert av: Genentech, Inc.

MAVERICC (Marker Evaluation for Avastin Research in CRC): A Randomized Phase II Study of Bevacizumab+mFOLFOX6 Vs. Bevacizumab+FOLFIRI With Biomarker Stratification in Patients With Previously Untreated Metastatic Colorectal Cancer

This will be a randomized, open-label, multicenter, Phase II study with primary objectives to assess whether expression of select chemotherapy markers is associated with progression-free survival (PFS) in participants treated with bevacizumab plus leucovorin, 5-fluorouracil, and oxaliplatin (mFOLFOX6) or bevacizumab plus leucovorin, 5-fluorouracil, and irinotecan (FOLFIRI). The study population will consist of participants with first-line mCRC.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Faktiske)

376

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
  • Estland
      • Tallinn, Estland, 13419
      • Tartu, Estland, 51014
  • Forente stater
    • Alabama
      • Birmingham, Alabama, Forente stater, 35294
    • Arkansas
      • Little Rock, Arkansas, Forente stater, 72205-7199
    • California
      • Bellflower, California, Forente stater, 90706
      • Duarte, California, Forente stater, 91010
      • Fountain Valley, California, Forente stater, 92708
      • Fresno, California, Forente stater, 93720
      • Hayward, California, Forente stater, 94545
      • Los Angeles, California, Forente stater, 90033
      • Oakland, California, Forente stater, 94611
      • Pleasant Hill, California, Forente stater, 94523
      • Roseville, California, Forente stater, 95661
      • Sacramento, California, Forente stater, 95817
      • Sacramento, California, Forente stater, 95825
      • San Francisco, California, Forente stater, 94115
      • San Jose, California, Forente stater, 95119
      • Santa Clara, California, Forente stater, 95051
      • South San Francisco, California, Forente stater, 94080
      • Vallejo, California, Forente stater, 94589
      • Walnut Creek, California, Forente stater, 94596
    • Colorado
      • Denver, Colorado, Forente stater, 80218
    • Connecticut
      • Stamford, Connecticut, Forente stater, 06902
      • Trumbull, Connecticut, Forente stater, 06611
    • Florida
      • Hollywood, Florida, Forente stater, 33021
      • Jacksonville, Florida, Forente stater, 32256
      • Miami, Florida, Forente stater, 33136
      • Port Saint Lucie, Florida, Forente stater, 34952
    • Idaho
      • Boise, Idaho, Forente stater, 83712
    • Illinois
      • Joliet, Illinois, Forente stater, 60435
      • Maywood, Illinois, Forente stater, 60153
      • Peoria, Illinois, Forente stater, 61615
    • Indiana
      • Goshen, Indiana, Forente stater, 46526
      • Indianapolis, Indiana, Forente stater, 46237
      • Terre Haute, Indiana, Forente stater, 47802
    • Kansas
      • Fairway, Kansas, Forente stater, 66205
    • Kentucky
      • Elizabethtown, Kentucky, Forente stater, 42791
    • Maine
      • Scarborough, Maine, Forente stater, 04074
    • Massachusetts
      • Burlington, Massachusetts, Forente stater, 01805
    • Montana
      • Billings, Montana, Forente stater, 59102
    • Nebraska
      • Lincoln, Nebraska, Forente stater, 68506
    • New Jersey
      • Cherry Hill, New Jersey, Forente stater, 08003
      • Manasquan, New Jersey, Forente stater, 08736
    • New Mexico
      • Albuquerque, New Mexico, Forente stater, 87131-5636
      • Albuquerque, New Mexico, Forente stater, 87106
      • Albuquerque, New Mexico, Forente stater, 87110
      • Farmington, New Mexico, Forente stater, 87401
      • Las Cruces, New Mexico, Forente stater, 88011
      • Santa Fe, New Mexico, Forente stater, 87505
    • New York
      • Rochester, New York, Forente stater, 14642
    • North Carolina
      • Durham, North Carolina, Forente stater, 27710
      • Greensboro, North Carolina, Forente stater, 27403
      • High Point, North Carolina, Forente stater, 27262
      • Washington, North Carolina, Forente stater, 27889
      • Winston-salem, North Carolina, Forente stater, 27103
    • Ohio
      • Columbus, Ohio, Forente stater, 43219
      • Toledo, Ohio, Forente stater, 43623
    • Oklahoma
      • Oklahoma City, Oklahoma, Forente stater, 73142
    • Pennsylvania
      • Dunmore, Pennsylvania, Forente stater, 18512
      • Media, Pennsylvania, Forente stater, 19063
      • Philadelphia, Pennsylvania, Forente stater, 19107
      • Pittsburgh, Pennsylvania, Forente stater, 15212
    • South Carolina
      • Charleston, South Carolina, Forente stater, 29414
    • Texas
      • Corpus Christi, Texas, Forente stater, 78404
      • Houston, Texas, Forente stater, 77090
    • Wisconsin
      • Madison, Wisconsin, Forente stater, 53792
      • Wauwatosa, Wisconsin, Forente stater, 53226
  • Irland
      • Cork, Irland
      • Dublin, Irland, 24
      • Galway, Irland
  • Norge
      • Oslo, Norge, 0407
  • Portugal
      • Coimbra, Portugal, 3000-075
      • Lisboa, Portugal, 1649-035
      • Porto, Portugal, 4200-072
  • Sveits
      • Aarau, Sveits, 5000
      • Basel, Sveits, 4031
      • Luzern, Sveits, 6004
      • Zürich, Sveits, 8063

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • Histologically or cytologically confirmed colorectal cancer (CRC) with at least one measurable metastatic lesion by RECIST Version 1.1
  • Archival tumor tissue sample must be requested and available prior to study entry. If no archival tumor tissue sample is available, a fresh biopsy tissue sample must be obtained but should be discussed first with the medical monitor. A copy of the local pathology report must be submitted along with the specimens.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Participants with treated brain metastases are eligible for study participation. Participants may not receive ongoing treatment with steroids at Screening. Anticonvulsants (at stable dose) are allowed. Treatment for brain metastases may be whole-brain radiotherapy, radiosurgery, neurosurgery, or a combination as deemed appropriate by the treating physician. Radiotherapy and stereotactic radiosurgery must be completed at least 28 days prior to randomization.
  • Female participants should not be pregnant or breastfeeding. Female participants with childbearing potential should agree to use effective, non-hormonal means of contraception during the study and for a period of at least 6 months following the last administration of study drugs. Female participants with an intact uterus (unless amenorrheic for the last 24 months) must have a negative serum pregnancy test within 7 days prior to randomization into the study.
  • Male participants must agree to use effective contraception during the study and for a period of at least 6 months following the last administration of study drugs, even if they have been surgically sterilized.

Exclusion Criteria:

  • Any prior systemic treatment for mCRC
  • Adjuvant chemotherapy for CRC completed <12 months
  • Evidence of Gilbert's syndrome or of homozygosity for the UGT1A1*28 allele
  • Known positivity for human immunodeficiency virus (HIV)
  • Malignancies other than mCRC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent
  • Radiotherapy to any site for any reason within 28 days prior to randomization, except for palliative radiotherapy to bone lesions within 14 days prior to randomization
  • Clinically detectable third-space fluid collections that cannot be controlled by drainage or other procedures prior to study entry
  • Treatment with any other investigational agent, or participation in another investigational drug trial within 28 days prior to randomization

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Bevacizumab + mFOLFOX6
Participants will receive bevacizumab plus mFOLFOX6 by intravenous (IV) infusion on Day 1 of each 2-week cycle until disease progression or unacceptable toxicity. Participants may be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin, with bevacizumab continued in 3-week cycles.
Legemiddel: 5-Fluorouracil
5-Fluorouracil 400 milligrams per meter-squared (mg/m^2) by IV bolus and subsequent 2400 mg/m^2 by IV infusion over 46 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.
Legemiddel: Bevacizumab
Bevacizumab 5 milligrams per kilogram (mg/kg) of body weight via IV infusion will be administered every 2 weeks until disease progression or unacceptable toxicity. If participants are discontinued from oxaliplatin or irinotecan due to unacceptable toxicity, bevacizumab may be given in 3-week cycles with capecitabine.
Andre navn:
  • Avastin
Legemiddel: Leucovorin
Leucovorin 400 mg/m^2 or dose deemed appropriate by Investigator via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.
Legemiddel: Oxaliplatin
Oxaliplatin 85 mg/m^2 via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.
Legemiddel: Capecitabine
Capecitabine 850 or 1000 mg/m^2 may be offered in the event of unacceptable toxicity to oxaliplatin or irinotecan, to be given orally twice a day on Days 1 to 14 in 3-week cycles.
Eksperimentell: Bevacizumab + FOLFIRI
Participants will receive bevacizumab plus FOLFIRI by IV infusion on Day 1 of each 2-week cycle until disease progression or unacceptable toxicity. Participants may be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan, with bevacizumab continued in 3-week cycles.
Legemiddel: 5-Fluorouracil
5-Fluorouracil 400 milligrams per meter-squared (mg/m^2) by IV bolus and subsequent 2400 mg/m^2 by IV infusion over 46 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.
Legemiddel: Bevacizumab
Bevacizumab 5 milligrams per kilogram (mg/kg) of body weight via IV infusion will be administered every 2 weeks until disease progression or unacceptable toxicity. If participants are discontinued from oxaliplatin or irinotecan due to unacceptable toxicity, bevacizumab may be given in 3-week cycles with capecitabine.
Andre navn:
  • Avastin
Legemiddel: Leucovorin
Leucovorin 400 mg/m^2 or dose deemed appropriate by Investigator via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.
Legemiddel: Capecitabine
Capecitabine 850 or 1000 mg/m^2 may be offered in the event of unacceptable toxicity to oxaliplatin or irinotecan, to be given orally twice a day on Days 1 to 14 in 3-week cycles.
Legemiddel: Irinotecan
Irinotecan 180 mg/m^2 via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Tidsramme: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as greater than or equal to (≥) 20 percent (%) increase in sum of largest diameters (LD) of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 millimeters (mm). Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% confidence interval (CI) was computed using the method of Brookmeyer and Crowley.
From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
PFS According to RECIST Version 1.1 in Participants With High ERCC-1 Levels
Tidsramme: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels
Tidsramme: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
PFS According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
Tidsramme: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
PFS According to RECIST Version 1.1 in Participants With High Vascular Endothelial Growth Factor (VEGF)-A Levels Versus Participants With Low VEGF-A Levels
Tidsramme: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
PFS According to RECIST Version 1.1 in Participants With High ERCC-1 and High VEGF-A Levels
Tidsramme: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
PFS According to RECIST Version 1.1 in Participants With High ERCC-1 and Low VEGF-A Levels
Tidsramme: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 and High VEGF-A Levels
Tidsramme: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 and Low VEGF-A Levels
Tidsramme: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Overall Survival (OS)
Tidsramme: From Baseline until death (maximum up to 45 months overall)
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. OS was defined as the time from randomization to death. The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death (maximum up to 45 months overall)
OS in Participants With High ERCC-1 Levels
Tidsramme: From Baseline until death (maximum up to 45 months overall)
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. OS was defined as the time from randomization to death. The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death (maximum up to 45 months overall)
OS in Participants With Low ERCC-1 Levels
Tidsramme: From Baseline until death (maximum up to 45 months overall)
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. OS was defined as the time from randomization to death. The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death (maximum up to 45 months overall)
OS in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
Tidsramme: From Baseline until death (maximum up to 45 months overall)
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. OS was defined as the time from randomization to death. The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death (maximum up to 45 months overall)
Percentage of Participants With Objective Response According to RECIST Version 1.1
Tidsramme: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Objective response was defined as complete response (CR) or partial response (PR) according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to less than (<) 10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. The percentage of participants with CR or PR was reported. The 95% CI was computed using normal approximation to the binomial distribution.
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High ERCC-1 Levels
Tidsramme: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Objective response was defined as CR or PR according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. The percentage of participants with CR or PR was reported. The 95% CI was computed using normal approximation to the binomial distribution.
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels
Tidsramme: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Objective response was defined as CR or PR according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. The percentage of participants with CR or PR was reported. The 95% CI was computed using normal approximation to the binomial distribution.
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
Tidsramme: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Objective response was defined as CR or PR according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. The percentage of participants with CR or PR was reported. The 95% CI was computed using normal approximation to the binomial distribution.
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Percentage of Participants With Disease Control According to RECIST Version 1.1
Tidsramme: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Disease control was defined as CR, PR, or stable disease (SD) according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study. The percentage of participants with CR, PR, or SD was reported. The 95% CI was computed using normal approximation to the binomial distribution.
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High ERCC-1 Levels
Tidsramme: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Disease control was defined as CR, PR, or SD according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study. The percentage of participants with CR, PR, or SD was reported. The 95% CI was computed using normal approximation to the binomial distribution.
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels
Tidsramme: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Disease control was defined as CR, PR, or SD according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study. The percentage of participants with CR, PR, or SD was reported. The 95% CI was computed using normal approximation to the binomial distribution.
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
Tidsramme: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Disease control was defined as CR, PR, or SD according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study. The percentage of participants with CR, PR, or SD was reported. The 95% CI was computed using normal approximation to the binomial distribution.
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Percentage of Participants With Liver Metastasis Resection
Tidsramme: At time of resective surgery during study (maximum up to 45 months overall)
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins. In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1. R2 was defined as macroscopic positive margins or incomplete resection at time of surgery. The percentage of participants with resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.
At time of resective surgery during study (maximum up to 45 months overall)
Percentage of Participants With Complete Liver Metastasis Resection
Tidsramme: At time of resective surgery during study (maximum up to 45 months overall)
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.
At time of resective surgery during study (maximum up to 45 months overall)
Percentage of Participants With Liver Metastasis Resection in Participants With High ERCC-1 Levels
Tidsramme: At time of resective surgery during study (maximum up to 45 months overall)
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins. In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1. R2 was defined as macroscopic positive margins or incomplete resection at time of surgery. The percentage of participants with resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.
At time of resective surgery during study (maximum up to 45 months overall)
Percentage of Participants With Complete Liver Metastasis Resection in Participants With High ERCC-1 Levels
Tidsramme: At time of resective surgery during study (maximum up to 45 months overall)
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.
At time of resective surgery during study (maximum up to 45 months overall)
Percentage of Participants With Liver Metastasis Resection in Participants With Low ERCC-1 Levels
Tidsramme: At time of resective surgery during study (maximum up to 45 months overall)
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins. In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1. R2 was defined as macroscopic positive margins or incomplete resection at time of surgery. The percentage of participants with resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.
At time of resective surgery during study (maximum up to 45 months overall)
Percentage of Participants With Complete Liver Metastasis Resection in Participants With Low ERCC-1 Levels
Tidsramme: At time of resective surgery during study (maximum up to 45 months overall)
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.
At time of resective surgery during study (maximum up to 45 months overall)
Percentage of Participants With Liver Metastasis Resection in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
Tidsramme: At time of resective surgery during study (maximum up to 45 months overall)
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins. In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1. R2 was defined as macroscopic positive margins or incomplete resection at time of surgery. The percentage of participants with resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.
At time of resective surgery during study (maximum up to 45 months overall)
Percentage of Participants With Complete Liver Metastasis Resection in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
Tidsramme: At time of resective surgery during study (maximum up to 45 months overall)
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.
At time of resective surgery during study (maximum up to 45 months overall)
PFS According to RECIST Version 1.1 in Participants With Wild-Type V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Versus Participants With Mutant KRAS
Tidsramme: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
OS in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
Tidsramme: From Baseline until death (maximum up to 45 months overall)
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. OS was defined as the time from randomization to death. The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death (maximum up to 45 months overall)
OS in Participants With Wild-Type KRAS Versus Participants With Mutant KRAS
Tidsramme: From Baseline until death (maximum up to 45 months overall)
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. OS was defined as the time from randomization to death. The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.
From Baseline until death (maximum up to 45 months overall)
Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
Tidsramme: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Objective response was defined as CR or PR according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. The percentage of participants with CR or PR was reported. The 95% CI was computed using normal approximation to the binomial distribution.
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With Wild-Type KRAS Versus Participants With Mutant KRAS
Tidsramme: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Objective response was defined as CR or PR according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. The percentage of participants with CR or PR was reported. The 95% CI was computed using normal approximation to the binomial distribution.
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
Tidsramme: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Disease control was defined as CR, PR, or SD according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study. The percentage of participants with CR, PR, or SD was reported. The 95% CI was computed using normal approximation to the binomial distribution.
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Percentage of Participants With Liver Metastasis Resection in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
Tidsramme: At time of resective surgery during study (maximum up to 45 months overall)
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins. In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1. R2 was defined as macroscopic positive margins or incomplete resection at time of surgery. The percentage of participants with resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.
At time of resective surgery during study (maximum up to 45 months overall)
Percentage of Participants With Complete Liver Metastasis Resection in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
Tidsramme: At time of resective surgery during study (maximum up to 45 months overall)
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.
At time of resective surgery during study (maximum up to 45 months overall)

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Genentech, Inc.

Etterforskere

  • Studieleder: Christiane Langer, M.D., Genentech, Inc.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. august 2011

Primær fullføring (Faktiske)

1. mai 2015

Studiet fullført (Faktiske)

1. juli 2015

Datoer for studieregistrering

Først innsendt

14. juni 2011

Først innsendt som oppfylte QC-kriteriene

15. juni 2011

Først lagt ut (Anslag)

16. juni 2011

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

11. august 2016

Siste oppdatering sendt inn som oppfylte QC-kriteriene

30. juni 2016

Sist bekreftet

1. juni 2016

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • ML25710
  • 2011-004755-39 (EudraCT-nummer)

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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