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

18 augustus 2017 bijgewerkt door: 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.

Studie Overzicht

Toestand

Beëindigd

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

280

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 75 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Geneesmiddel: 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.
Geneesmiddel: 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.
Andere namen:
  • Avastin
Geneesmiddel: 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.
Andere namen:
  • Xeloda
Geneesmiddel: 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.
Geneesmiddel: 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.
Andere namen:
  • leucovorine
Geneesmiddel: 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 .
Experimenteel: 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.
Geneesmiddel: 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.
Geneesmiddel: 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.
Andere namen:
  • Avastin
Geneesmiddel: 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.
Andere namen:
  • Xeloda
Geneesmiddel: 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.
Geneesmiddel: 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.
Andere namen:
  • leucovorine
Geneesmiddel: 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 .
Experimenteel: 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.
Geneesmiddel: 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.
Geneesmiddel: 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.
Andere namen:
  • Avastin
Geneesmiddel: 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.
Andere namen:
  • Xeloda
Geneesmiddel: 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.
Andere namen:
  • leucovorine
Geneesmiddel: 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 .

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Percentage of Participants With Overall Response During First-Line Therapy (ORR1)
Tijdsspanne: 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)
Tijdsspanne: 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)

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Time to PFS2
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Hoffmann-La Roche

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

23 januari 2013

Primaire voltooiing (Werkelijk)

14 maart 2016

Studie voltooiing (Werkelijk)

14 maart 2016

Studieregistratiedata

Eerst ingediend

9 januari 2013

Eerst ingediend dat voldeed aan de QC-criteria

9 januari 2013

Eerst geplaatst (Schatting)

10 januari 2013

Updates van studierecords

Laatste update geplaatst (Werkelijk)

18 september 2017

Laatste update ingediend die voldeed aan QC-criteria

18 augustus 2017

Laatst geverifieerd

1 augustus 2017

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • ML28442

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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