Colorectal NeoplasmsPhase 2STEAMNCT01765582
Sequential and Concurrent FOLFOXIRI/Bevacizumab Regimens Versus FOLFOX/Bevacizumab in First-Line Metastatic Colorectal Cancer
A Phase 2 study testing 5-fluorouracil, bevacizumab and capecitabine in people with Colorectal Neoplasms, run by Hoffmann-La Roche at 45 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Neoplasms
- What is being tested?
- 5-fluorouracil, bevacizumab and capecitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- 45 sitesUnited States
- Study dates
- 23 Jan 2013to 14 Mar 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
45 sites in 1 country.
45 sites in 1 country
United States45 sites
St. Joseph Mercy Hospital; Cancer Care Center.
Ann Arbor, Michigan, 48106
University Cancer & Blood Center, LLC
Athens, Georgia, 30607
Emory University Clinic
Atlanta, Georgia, 30322
Johns Hopkins Univ; Bunting Blaustein Cancer Center
Baltimore, Maryland, 21231
Tufts Medical Center
Boston, Massachusetts, 02111
Chattanooga Oncology and Hematology Associates, PC
Chattanooga, Tennessee, 37404
Cheyenne Oncology & Hematology Associates
Cheyenne, Wyoming, 82001
Oncology Hematology Care Inc
Cincinnati, Ohio, 45242
UT Southwestern MC at Dallas
Dallas, Texas, 75390-9063
Kaiser Permanente - Franklin
Denver, Colorado, 80205
Karmanos Cancer Institute..
Detroit, Michigan, 48201
Florida Cancer Specialists - Fort Myers (Colonial Center Dr)
Fort Myers, Florida, 33905
Ctr for Cancer and Blood Disorders
Fort Worth, Texas, 76104
West Clinic
Germantown, Tennessee, 38138
Vince Lombardi Cancer Center
Green Bay, Wisconsin, 54311
Ingalls Memorial Hosp
Harvey, Illinois, 60426
Milton S. Hershey Medical Center; Penn State Cancer Inst.
Hershey, Pennsylvania, 17033
Seattle Cancer Care Alliance - Evergreen Health
Kirkland, Washington, 98034
Dartmouth Hitchcock Med Center
Lebanon, New Hampshire, 03756
University of Kentucky Medical Center
Lexington, Kentucky, 40536
Southeast Nebraska Cancer Center;; Southeast Nebraska Hematology and Oncology
Lincoln, Nebraska, 68510
Long Beach Memorial Medical Center; Oncology
Long Beach, California, 90806
LAC-USC Medical Center
Los Angeles, California, 90033
USC Norris Cancer Center
Los Angeles, California, 90033
Central Georgia Cancer Care PC
Macon, Georgia, 31201
Medical College of Wisconsin; Dept Froedtert Clin Can Ctr
Milwaukee, Wisconsin, 53226
University of South Alabama; Mitchell Cancer Institute
Mobile, Alabama, 36604
Pacific Cancer Care - Monterey
Monterey, California, 93940
Edward Cancer Center Naperville
Naperville, Illinois, 60540
Sarah Cannon Cancer Center and Research Institute
Nashville, Tennessee, 37203
Yale Cancer Center
New Haven, Connecticut, 06520
University of Oklahoma; Stephenson Oklahoma Canc Ctr
Oklahoma City, Oklahoma, 73104
Nebraska Methodist Hospital; Cancer Center
Omaha, Nebraska, 68114
Edward Cancer Center Plainfield
Plainfield, Illinois, 60585
Virginia Cancer Institute
Richmond, Virginia, 23226
Sacramento Center for Hematolo
Sacramento, California, 95816
Pacific Cancer Care
Salinas, California, 93901
Summit Cancer Care PC
Savannah, Georgia, 31405
Seattle Cancer Care Alliance
Seattle, Washington, 98109
Medical Oncology Associates
Spokane, Washington, 99208
Washington University School of Medicine
St Louis, Missouri, 63110
Florida Cancer Specialist, North Region
St. Petersburg, Florida, 33705
Scott and White Hospital; Cancer Center
Temple, Texas, 76508
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
Aurora Research Institute
Wauwatosa, Wisconsin, 53226
About this study
Official title: 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.
- Conditions
- Colorectal Neoplasms
- Being tested
- 5-fluorouracil, bevacizumab, capecitabine, irinotecan, folinic acid
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-fluorouracilDrug
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.
bevacizumabDrug
Also called Avastin
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.
capecitabineDrug
Also called Xeloda
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.
irinotecanDrug
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.
folinic acidDrug
Also called leucovorin
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.
oxaliplatinDrug
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 .
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Concurrent FOLFOXIRI + Bevacizumab | Experimental | 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. Receives: Drug: 5-fluorouracil; Drug: bevacizumab; Drug: capecitabine; Drug: irinotecan; Drug: folinic acid; Drug: oxaliplatin |
| Arm B: Sequential FOLFOXIRI + Bevacizumab | Experimental | 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. Receives: Drug: 5-fluorouracil; Drug: bevacizumab; Drug: capecitabine; Drug: irinotecan; Drug: folinic acid; Drug: oxaliplatin |
| Arm C: FOLFOX + Bevacizumab | Experimental | 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. Receives: Drug: 5-fluorouracil; Drug: bevacizumab; Drug: capecitabine; Drug: folinic acid; Drug: oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Overall Response During First-Line Therapy (ORR1)
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
Measured: 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)
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.
Measured: Randomization up to disease progression during first-line therapy or death, whichever occurs first (up to approximately 3 years)
Secondary outcomes (5)
Time to PFS2
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.
Measured: Randomization up to disease progression during second-line therapy or death, whichever occurs first (up to approximately 3 years)
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death from any cause.
Measured: Randomization until death due to any cause (up to approximately 3 years)
Proportion of Participants Who Underwent Liver Metastases Resections
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.
Measured: 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
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.
Measured: Randomization up to approximately 3 years
Percentage of Participants With Adverse Events
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.
Measured: Randomization up to approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2013 (estimated)
- Study start23 Jan 2013
- Primary completion14 Mar 2016
- Study completion14 Mar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 280 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01765582
- Sponsor's protocol ID
- ML28442
- Acronym
- STEAM
- Status last verified
- Aug 2017
- First submitted
- 9 Jan 2013
- Last updated
- 18 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll HJ, Di Maio M. Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer. J Clin Oncol. 2020 Aug 20:JCO2001225. doi: 10.1200/JCO.20.01225. Online ahead of print.
PubMed 32816630Hurwitz HI, Tan BR, Reeves JA, Xiong H, Somer B, Lenz HJ, Hochster HS, Scappaticci F, Palma JF, Price R, Lee JJ, Nicholas A, Sommer N, Bendell J. Phase II Randomized Trial of Sequential or Concurrent FOLFOXIRI-Bevacizumab Versus FOLFOX-Bevacizumab for Metastatic Colorectal Cancer (STEAM). Oncologist. 2019 Jul;24(7):921-932. doi: 10.1634/theoncologist.2018-0344. Epub 2018 Dec 14.
PubMed 30552157
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Steam (Sequencing Triplet With Avastin and Maintenance): FOLFOXIRI/Bevacizumab Regimens (Concurrent and Sequential) vs. FOLFOX/Bevacizumab in First-Line Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01765582
- Acronym / sponsor ID
- STEAM / ML28442
- Conditions
- Colorectal Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 280 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 23 Jan 2013 (actual)
- Primary completion
- 14 Mar 2016 (actual)
- Study completion
- 14 Mar 2016 (actual)
- First posted
- 10 Jan 2013 (estimated)
- Results
- Posted 18 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A: Concurrent FOLFOXIRI + Bevacizumab | Experimental | Drug: 5-fluorouracil, Drug: bevacizumab, Drug: capecitabine, Drug: irinotecan, Drug: folinic acid, Drug: oxaliplatinParticipants 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. |
| Arm B: Sequential FOLFOXIRI + Bevacizumab | Experimental | Drug: 5-fluorouracil, Drug: bevacizumab, Drug: capecitabine, Drug: irinotecan, Drug: folinic acid, Drug: oxaliplatinParticipants 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. |
| Arm C: FOLFOX + Bevacizumab | Experimental | Drug: 5-fluorouracil, Drug: bevacizumab, Drug: capecitabine, Drug: folinic acid, Drug: oxaliplatinParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5-fluorouracilParticipants 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. | Drug | Arm A: Concurrent FOLFOXIRI + Bevacizumab, Arm B: Sequential FOLFOXIRI + Bevacizumab, Arm C: FOLFOX + Bevacizumab |
| bevacizumabAlso: AvastinParticipants 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. | Drug | Arm A: Concurrent FOLFOXIRI + Bevacizumab, Arm B: Sequential FOLFOXIRI + Bevacizumab, Arm C: FOLFOX + Bevacizumab |
| capecitabineAlso: XelodaParticipants 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. | Drug | Arm A: Concurrent FOLFOXIRI + Bevacizumab, Arm B: Sequential FOLFOXIRI + Bevacizumab, Arm C: FOLFOX + Bevacizumab |
| irinotecanParticipants 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. | Drug | Arm A: Concurrent FOLFOXIRI + Bevacizumab, Arm B: Sequential FOLFOXIRI + Bevacizumab |
| folinic acidAlso: leucovorinParticipants 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. | Drug | Arm A: Concurrent FOLFOXIRI + Bevacizumab, Arm B: Sequential FOLFOXIRI + Bevacizumab, Arm C: FOLFOX + Bevacizumab |
| oxaliplatinParticipants 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 . | Drug | Arm A: Concurrent FOLFOXIRI + Bevacizumab, Arm B: Sequential FOLFOXIRI + Bevacizumab, Arm C: FOLFOX + Bevacizumab |
Primary outcome
Percentage of Participants With Overall Response During First-Line Therapy (ORR1)
Time frame: 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
Progression-Free Survival During First-Line Therapy (PFS1)
Time frame: 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.
5 secondary outcomes
Time to PFS2
Time frame: Randomization up to disease progression during second-line therapy or death, whichever occurs first (up to approximately 3 years)
Overall Survival (OS)
Time frame: Randomization until death due to any cause (up to approximately 3 years)
Proportion of Participants Who Underwent Liver Metastases Resections
Time frame: 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
Time frame: Randomization up to approximately 3 years
Percentage of Participants With Adverse Events
Time frame: Randomization up to approximately 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32816630Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll HJ, Di Maio M. Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer. J Clin Oncol. 2020 Aug 20:JCO2001225. doi: 10.1200/JCO.20.01225. Online ahead of print.
- Derived from this study: PubMed 30552157Hurwitz HI, Tan BR, Reeves JA, Xiong H, Somer B, Lenz HJ, Hochster HS, Scappaticci F, Palma JF, Price R, Lee JJ, Nicholas A, Sommer N, Bendell J. Phase II Randomized Trial of Sequential or Concurrent FOLFOXIRI-Bevacizumab Versus FOLFOX-Bevacizumab for Metastatic Colorectal Cancer (STEAM). Oncologist. 2019 Jul;24(7):921-932. doi: 10.1634/theoncologist.2018-0344. Epub 2018 Dec 14.
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Colorectal Neoplasms, Neoplasms
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Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
45 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 5-fluorouracil, bevacizumab and capecitabine in people with Colorectal Neoplasms, run by Hoffmann-La Roche at 45 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Overall Response During First-Line Therapy (ORR1) (time frame: Randomization up to disease progression during first-line therapy or death, whichever occurs first (up to approximately 3 years)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01765582, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2017.