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

18 agosto 2017 aggiornato da: 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.

Panoramica dello studio

Stato

Terminato

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Effettivo)

280

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 75 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Droga: 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.
Droga: 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.
Altri nomi:
  • Avastin
Droga: 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.
Altri nomi:
  • Xeloda
Droga: 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.
Droga: 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.
Altri nomi:
  • leucovorin
Droga: 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 .
Sperimentale: 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.
Droga: 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.
Droga: 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.
Altri nomi:
  • Avastin
Droga: 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.
Altri nomi:
  • Xeloda
Droga: 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.
Droga: 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.
Altri nomi:
  • leucovorin
Droga: 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 .
Sperimentale: 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.
Droga: 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.
Droga: 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.
Altri nomi:
  • Avastin
Droga: 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.
Altri nomi:
  • Xeloda
Droga: 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.
Altri nomi:
  • leucovorin
Droga: 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 .

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Percentage of Participants With Overall Response During First-Line Therapy (ORR1)
Lasso di tempo: 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)
Lasso di tempo: 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)

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Time to PFS2
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Hoffmann-La Roche

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

23 gennaio 2013

Completamento primario (Effettivo)

14 marzo 2016

Completamento dello studio (Effettivo)

14 marzo 2016

Date di iscrizione allo studio

Primo inviato

9 gennaio 2013

Primo inviato che soddisfa i criteri di controllo qualità

9 gennaio 2013

Primo Inserito (Stima)

10 gennaio 2013

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

18 settembre 2017

Ultimo aggiornamento inviato che soddisfa i criteri QC

18 agosto 2017

Ultimo verificato

1 agosto 2017

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • ML28442

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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