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Sequential and Concurrent FOLFOXIRI/Bevacizumab Regimens Versus FOLFOX/Bevacizumab in First-Line Metastatic Colorectal Cancer (STEAM)

18 augusti 2017 uppdaterad av: Hoffmann-La Roche

Steam (Sequencing Triplet With Avastin and Maintenance): FOLFOXIRI/Bevacizumab Regimens (Concurrent and Sequential) vs. FOLFOX/Bevacizumab in First-Line Metastatic Colorectal Cancer

This randomized, open-label, multicenter study will evaluate the efficacy and safety of folinic acid (leucovorin), 5-fluorouracil (5-FU), oxaliplatin, and irinotecan (FOLFOXIRI) / bevacizumab regimens (concurrent and sequential) versus folinic acid (leucovorin), 5-fluorouracil, and oxaliplatin (FOLFOX) / bevacizumab in first-line in participants with metastatic colorectal cancer. Participants will be randomized to receive bevacizumab 5 milligrams per kilogram (mg/kg) intravenously every 2 weeks with either concurrent or sequential FOLFOXIRI or with FOLFOX for 4 to 6 months of induction therapy, followed by maintenance therapy with bevacizumab plus either leucovorin/5-fluorouracil or capecitabine until disease progression occurs. After disease progression, participants will receive treatment with a fluoropyrimidine-based chemotherapy plus bevacizumab.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Studietyp

Interventionell

Inskrivning (Faktisk)

280

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Förenta staterna
    • Alabama
      • Mobile, Alabama, Förenta staterna, 36604
        • University of South Alabama; Mitchell Cancer Institute
    • California
      • Long Beach, California, Förenta staterna, 90806
        • Long Beach Memorial Medical Center; Oncology
      • Los Angeles, California, Förenta staterna, 90033
        • USC Norris Cancer Center
      • Los Angeles, California, Förenta staterna, 90033
        • LAC-USC Medical Center
      • Monterey, California, Förenta staterna, 93940
        • Pacific Cancer Care - Monterey
      • Sacramento, California, Förenta staterna, 95816
        • Sacramento Center for Hematolo
      • Salinas, California, Förenta staterna, 93901
        • Pacific Cancer Care
    • Colorado
      • Denver, Colorado, Förenta staterna, 80205
        • Kaiser Permanente - Franklin
    • Connecticut
      • New Haven, Connecticut, Förenta staterna, 06520
        • Yale Cancer Center
    • District of Columbia
      • Washington, D.C., District of Columbia, Förenta staterna, 20016
        • Sibley Memorial Hospital
    • Florida
      • Fort Myers, Florida, Förenta staterna, 33905
        • Florida Cancer Specialists - Fort Myers (Colonial Center Dr)
      • Saint Petersburg, Florida, Förenta staterna, 33705
        • Florida Cancer Specialist, North Region
    • Georgia
      • Athens, Georgia, Förenta staterna, 30607
        • University Cancer & Blood Center, LLC
      • Atlanta, Georgia, Förenta staterna, 30322
        • Emory University Clinic
      • Macon, Georgia, Förenta staterna, 31201
        • Central Georgia Cancer Care PC
      • Savannah, Georgia, Förenta staterna, 31405
        • Summit Cancer Care PC
    • Illinois
      • Harvey, Illinois, Förenta staterna, 60426
        • Ingalls Memorial Hosp
      • Naperville, Illinois, Förenta staterna, 60540
        • Edward Cancer Center Naperville
      • Plainfield, Illinois, Förenta staterna, 60585
        • Edward Cancer Center Plainfield
    • Kentucky
      • Lexington, Kentucky, Förenta staterna, 40536
        • University of Kentucky Medical Center
    • Maryland
      • Baltimore, Maryland, Förenta staterna, 21231
        • Johns Hopkins Univ; Bunting Blaustein Cancer Center
    • Massachusetts
      • Boston, Massachusetts, Förenta staterna, 02111
        • Tufts Medical Center
    • Michigan
      • Ann Arbor, Michigan, Förenta staterna, 48106
        • St. Joseph Mercy Hospital; Cancer Care Center.
      • Detroit, Michigan, Förenta staterna, 48201
        • Karmanos Cancer Institute..
    • Missouri
      • Saint Louis, Missouri, Förenta staterna, 63110
        • Washington University School of Medicine
    • Nebraska
      • Lincoln, Nebraska, Förenta staterna, 68510
        • Southeast Nebraska Cancer Center;; Southeast Nebraska Hematology and Oncology
      • Omaha, Nebraska, Förenta staterna, 68114
        • Nebraska Methodist Hospital; Cancer Center
    • New Hampshire
      • Lebanon, New Hampshire, Förenta staterna, 03756
        • Dartmouth Hitchcock Med Center
    • Ohio
      • Cincinnati, Ohio, Förenta staterna, 45242
        • Oncology Hematology Care Inc
    • Oklahoma
      • Oklahoma City, Oklahoma, Förenta staterna, 73104
        • University of Oklahoma; Stephenson Oklahoma Canc Ctr
    • Pennsylvania
      • Hershey, Pennsylvania, Förenta staterna, 17033
        • Milton S. Hershey Medical Center; Penn State Cancer Inst.
    • Tennessee
      • Chattanooga, Tennessee, Förenta staterna, 37404
        • Chattanooga Oncology and Hematology Associates, PC
      • Germantown, Tennessee, Förenta staterna, 38138
        • West Clinic
      • Nashville, Tennessee, Förenta staterna, 37203
        • Sarah Cannon Cancer Center and Research Institute
    • Texas
      • Dallas, Texas, Förenta staterna, 75390-9063
        • UT Southwestern MC at Dallas
      • Fort Worth, Texas, Förenta staterna, 76104
        • Ctr For Cancer And Blood Disorders
      • Temple, Texas, Förenta staterna, 76508
        • Scott and White Hospital; Cancer Center
    • Virginia
      • Richmond, Virginia, Förenta staterna, 23226
        • Virginia Cancer Institute
    • Washington
      • Kirkland, Washington, Förenta staterna, 98034
        • Seattle Cancer Care Alliance - Evergreen Health
      • Seattle, Washington, Förenta staterna, 98109
        • Seattle Cancer Care Alliance
      • Spokane, Washington, Förenta staterna, 99208
        • Medical Oncology Associates
    • Wisconsin
      • Green Bay, Wisconsin, Förenta staterna, 54311
        • Vince Lombardi Cancer Center
      • Milwaukee, Wisconsin, Förenta staterna, 53226
        • Medical College of Wisconsin; Dept Froedtert Clin Can Ctr
      • Wauwatosa, Wisconsin, Förenta staterna, 53226
        • Aurora Research Institute
    • Wyoming
      • Cheyenne, Wyoming, Förenta staterna, 82001
        • Cheyenne Oncology & Hematology Associates

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 75 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  • Histologically confirmed colorectal cancer with at least one measurable metastatic lesion by RECIST v 1.1, that is considered unresectable at baseline
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 if age less than (<) 71 years; ECOG status of 0 if age 71 to 75 years
  • Adequate hematological, renal and liver function
  • 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
  • Females of childbearing potential and males must agree to use effective contraception as defined by protocol during the treatment period and for at least 6 months after the last dose of study drug

Exclusion Criteria:

  • Any prior treatment for metastatic colorectal cancer, except for use of palliative radiosensitizers
  • Adjuvant chemotherapy for colorectal cancer completed < 12 months prior to study consent
  • Sensory peripheral neuropathy greater than or equal to (>/=) Grade 2
  • Evidence of Gilbert's Syndrome or homozygosity for the Uridine 5-diphospho-glucuronosyltransferase (UGT) 1A1*28 allele
  • Positive for human immunodeficiency virus (HIV) infection
  • Malignancies other than metastatic colorectal cancer 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 significant third-space fluid collections (e.g. ascites or pleural effusion) 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
  • Any disease or condition or laboratory finding giving reasonable suspicion of disease or condition that contraindicates the use of bevacizumab or puts the participant at high risk for treatment-related complications
  • Inadequately controlled hypertension
  • Clinically significant (that is [i.e.] active) cardiovascular disease (For example [e.g.] cerebrovascular accident or myocardial infarction within 6 months prior to randomization), unstable angina, congestive heart failure (New York Heart Association Class >/= II) or serious cardiac arrhythmia that is uncontrolled by medication or may interfere with the administration of the study treatment
  • Known hypersensitivity to bevacizumab or any of its excipients or any other study drug

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Arm A: Concurrent FOLFOXIRI + Bevacizumab
Participants will receive concurrent FOLFOXIRI along with 5 mg/kg of bevacizumab with treatment cycle of 2 weeks during first 4 month induction phase (plus optional 2 months of induction for participants who exhibit good response and tolerate the regimen) followed by administration of 5-FU with bevacizumab or capecitabine with bevacizumab as per investigator's discretion in maintenance phase. Following progression on first-line therapy (PD1), bevacizumab (dose equivalent, 2.5 mg/kg/week) will be administered as second-line therapy in combination with fluoropyrimidine based chemotherapy at the investigator's discretion.
Läkemedel: 5-fluorouracil
Participants in Arm A will receive 3200 milligrams per square meter (mg/m^2) by 48-hour continuous intravenous (IV) infusion every 2 weeks, during the 4-6 months' induction followed by maintenance therapy including bolus dose of 400 mg/m^2, followed by a 46-hour continuous infusion (2400 mg/m^2) every 2 weeks per investigator's discretion. Participants in Arm B and C will receive a bolus dose of 400 mg/m^2, followed by a 46-hour continuous infusion (2400 mg/m^2) every 2 weeks during the 4-6 months of induction and maintenance per investigator's discretion.
Läkemedel: bevacizumab
Participants will receive 5 mg/kg IV every 2 weeks during the first 4-6 months induction phase, followed by 5 mg/kg IV every 2 weeks or 7.5 mg/kg IV every 3 weeks during maintenance therapy, and 2.5 mg/kg per week reinduction after disease progression.
Andra namn:
  • Avastin
Läkemedel: capecitabine
Participants will receive 1000 or 850 mg/kg orally twice daily as per investigator's discretion on Day 1 to 14, repeated every 3 weeks in maintenance phase.
Andra namn:
  • Xeloda
Läkemedel: irinotecan
Participants will receive IV infusion of 165 mg/m^2 over 1 hour every 2 weeks (Arm A) or IV infusion of 180 mg/m^2 over 1 hour in 2 x 2 weeks cycles alternating months (in Arm B), during 4-6 months induction phase.
Läkemedel: folinic acid
Participants will receive IV infusion of 200 mg/m^² (Arm A) or 400 mg/m^2 (Arm B or C) over 2 hours every 2 weeks, during 4-6 months induction phase followed by IV infusion of 400 mg/m^2 in the maintenance therapy.
Andra namn:
  • leukovorin
Läkemedel: oxaliplatin
Participants will receive 85 mg/m^2 over 2 hours as IV infusion every 2 weeks (Arm A, C ) or 2 x 2 week cycles alternating months (Arm B), during 4-6 months induction phase .
Experimentell: Arm B: Sequential FOLFOXIRI + Bevacizumab
Participants will receive alternating 4-week administrations of FOLFOX/bevacizumab and folinic acid (leucovorin), 5-FU, and irinotecan (FOLFIRI) /Bevacizumab with a treatment cycle of 2 weeks during first 4-month induction phase (plus optional 2 months of induction for participants who exhibit good response and tolerate the regimen) followed by administration of 5-FU with bevacizumab or capecitabine with bevacizumab as per investigator's discretion in maintenance phase. Following progression on first-line therapy (PD1), bevacizumab (dose equivalent, 2.5 mg/kg/week) will be administered as second-line therapy in combination with fluoropyrimidine based chemotherapy at the investigator's discretion.
Läkemedel: 5-fluorouracil
Participants in Arm A will receive 3200 milligrams per square meter (mg/m^2) by 48-hour continuous intravenous (IV) infusion every 2 weeks, during the 4-6 months' induction followed by maintenance therapy including bolus dose of 400 mg/m^2, followed by a 46-hour continuous infusion (2400 mg/m^2) every 2 weeks per investigator's discretion. Participants in Arm B and C will receive a bolus dose of 400 mg/m^2, followed by a 46-hour continuous infusion (2400 mg/m^2) every 2 weeks during the 4-6 months of induction and maintenance per investigator's discretion.
Läkemedel: bevacizumab
Participants will receive 5 mg/kg IV every 2 weeks during the first 4-6 months induction phase, followed by 5 mg/kg IV every 2 weeks or 7.5 mg/kg IV every 3 weeks during maintenance therapy, and 2.5 mg/kg per week reinduction after disease progression.
Andra namn:
  • Avastin
Läkemedel: capecitabine
Participants will receive 1000 or 850 mg/kg orally twice daily as per investigator's discretion on Day 1 to 14, repeated every 3 weeks in maintenance phase.
Andra namn:
  • Xeloda
Läkemedel: irinotecan
Participants will receive IV infusion of 165 mg/m^2 over 1 hour every 2 weeks (Arm A) or IV infusion of 180 mg/m^2 over 1 hour in 2 x 2 weeks cycles alternating months (in Arm B), during 4-6 months induction phase.
Läkemedel: folinic acid
Participants will receive IV infusion of 200 mg/m^² (Arm A) or 400 mg/m^2 (Arm B or C) over 2 hours every 2 weeks, during 4-6 months induction phase followed by IV infusion of 400 mg/m^2 in the maintenance therapy.
Andra namn:
  • leukovorin
Läkemedel: oxaliplatin
Participants will receive 85 mg/m^2 over 2 hours as IV infusion every 2 weeks (Arm A, C ) or 2 x 2 week cycles alternating months (Arm B), during 4-6 months induction phase .
Experimentell: Arm C: FOLFOX + Bevacizumab
Participants will receive FOLFOX along with 5 mg/kg of bevacizumab with treatment cycle of 2 weeks during first 4-month induction phase (plus optional 2 months of induction for participants who exhibit good response and tolerate the regimen) followed by administration of 5-FU with bevacizumab or capecitabine with bevacizumab as per investigator's discretion in maintenance phase. Following progression on first-line therapy (PD1), bevacizumab (dose equivalent, 2.5 mg/kg/week) will be administered as second-line therapy in combination with fluoropyrimidine based chemotherapy at the investigator's discretion.
Läkemedel: 5-fluorouracil
Participants in Arm A will receive 3200 milligrams per square meter (mg/m^2) by 48-hour continuous intravenous (IV) infusion every 2 weeks, during the 4-6 months' induction followed by maintenance therapy including bolus dose of 400 mg/m^2, followed by a 46-hour continuous infusion (2400 mg/m^2) every 2 weeks per investigator's discretion. Participants in Arm B and C will receive a bolus dose of 400 mg/m^2, followed by a 46-hour continuous infusion (2400 mg/m^2) every 2 weeks during the 4-6 months of induction and maintenance per investigator's discretion.
Läkemedel: bevacizumab
Participants will receive 5 mg/kg IV every 2 weeks during the first 4-6 months induction phase, followed by 5 mg/kg IV every 2 weeks or 7.5 mg/kg IV every 3 weeks during maintenance therapy, and 2.5 mg/kg per week reinduction after disease progression.
Andra namn:
  • Avastin
Läkemedel: capecitabine
Participants will receive 1000 or 850 mg/kg orally twice daily as per investigator's discretion on Day 1 to 14, repeated every 3 weeks in maintenance phase.
Andra namn:
  • Xeloda
Läkemedel: folinic acid
Participants will receive IV infusion of 200 mg/m^² (Arm A) or 400 mg/m^2 (Arm B or C) over 2 hours every 2 weeks, during 4-6 months induction phase followed by IV infusion of 400 mg/m^2 in the maintenance therapy.
Andra namn:
  • leukovorin
Läkemedel: oxaliplatin
Participants will receive 85 mg/m^2 over 2 hours as IV infusion every 2 weeks (Arm A, C ) or 2 x 2 week cycles alternating months (Arm B), during 4-6 months induction phase .

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Percentage of Participants With Overall Response During First-Line Therapy (ORR1)
Tidsram: Randomization up to disease progression during first-line therapy or death, whichever occurs first (up to approximately 3 years)
ORR1 was the percentage of participants with complete response (CR) or partial response (PR) during first-line therapy as assessed by investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1). CR was defined as disappearance of all extranodal target lesions and all pathological lymph nodes had to have decreased to <10 millimeter (mm) in short axis. PR was defined as at least a 30% decrease in the sum of longest diameters of target lesions, taking as reference the baseline sum diameters. ORR1 = CR + PR
Randomization up to disease progression during first-line therapy or death, whichever occurs first (up to approximately 3 years)
Progression-Free Survival During First-Line Therapy (PFS1)
Tidsram: Randomization up to disease progression during first-line therapy or death, whichever occurs first (up to approximately 3 years)
PFS1 was defined as time from randomization to the first occurrence of disease progression during first-line therapy, as assessed by the Investigator using RECIST v1.1, or death from any cause, whichever occurs first. Disease progression was defined as sum of longest diameters increased by at least 20% from the smallest value on study. The sum of longest diameters must also demonstrate an absolute increase of at least 5 mm.
Randomization up to disease progression during first-line therapy or death, whichever occurs first (up to approximately 3 years)

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Time to PFS2
Tidsram: Randomization up to disease progression during second-line therapy or death, whichever occurs first (up to approximately 3 years)
Time to PFS2 was defined as time from randomization to the first occurrence of disease progression after reinduction of second-line therapy, as assessed by the Investigator using RECIST v1.1, or death from any cause, whichever occurs first. Disease progression was defined as sum of longest diameters increased by at least 20% from the smallest value on study. The sum of longest diameters must also demonstrate an absolute increase of at least 5mm.
Randomization up to disease progression during second-line therapy or death, whichever occurs first (up to approximately 3 years)
Overall Survival (OS)
Tidsram: Randomization until death due to any cause (up to approximately 3 years)
OS was defined as the time from the date of randomization to the date of death from any cause.
Randomization until death due to any cause (up to approximately 3 years)
Proportion of Participants Who Underwent Liver Metastases Resections
Tidsram: Randomization up to approximately 3 years
Reported here is the proportion of participants who underwent liver metastases resections calculated as follows: number of participants who underwent liver metastases resections divided by total number of participants in each arm.
Randomization up to approximately 3 years
Proportion of Participants Considered by the Investigator to be Unresectable on Study Enrollment Who Subsequently Underwent Attempted Curative Resections of Metastases
Tidsram: Randomization up to approximately 3 years
The proportion of participants considered by the investigator to be unresectable at study enrollment who subsequently underwent attempted curative resections of metastases was calculated as follows: number of participants considered by the investigator to be unresectable at study enrollment who subsequently underwent attempted curative resections of metastases divided by total number of participants in each arm. This outcome represents a measure of the rate of conversion from unresectable to resectable disease.
Randomization up to approximately 3 years
Percentage of Participants With Adverse Events
Tidsram: Randomization up to approximately 3 years
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Randomization up to approximately 3 years

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Hoffmann-La Roche

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

23 januari 2013

Primärt slutförande (Faktisk)

14 mars 2016

Avslutad studie (Faktisk)

14 mars 2016

Studieregistreringsdatum

Först inskickad

9 januari 2013

Först inskickad som uppfyllde QC-kriterierna

9 januari 2013

Första postat (Uppskatta)

10 januari 2013

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

18 september 2017

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

18 augusti 2017

Senast verifierad

1 augusti 2017

Mer information

Termer relaterade till denna studie

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • ML28442

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

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