Clinical trial · Interventional
Sequential and Concurrent FOLFOXIRI/Bevacizumab Regimens Versus FOLFOX/Bevacizumab in First-Line Metastatic Colorectal Cancer
Steam (Sequencing Triplet With Avastin and Maintenance): FOLFOXIRI/Bevacizumab Regimens (Concurrent and Sequential) vs. FOLFOX/Bevacizumab in First-Line Metastatic Colorectal Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Colorectal Neoplasms | Colorectal Neoplasm | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (6)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| 5-fluorouracil | Drug | Fluorouracil | ALIAS |
| bevacizumab | Drug | Bevacizumab | ALIAS |
| capecitabine | Drug | Capecitabine | ALIAS |
| folinic acid | Drug | — | UNRESOLVED |
| irinotecan | Drug | Irinotecan | ALIAS |
| oxaliplatin | Drug | Oxaliplatin | ALIAS |
Design
Arms and outcomes
Arms (3)
- type
- EXPERIMENTAL
- label
- Arm A: Concurrent FOLFOXIRI + Bevacizumab
- description
- 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.
- interventionNames
- Drug: 5-fluorouracil
- Drug: bevacizumab
- Drug: capecitabine
- Drug: irinotecan
- Drug: folinic acid
- Drug: oxaliplatin
- type
- EXPERIMENTAL
- label
- Arm B: Sequential FOLFOXIRI + Bevacizumab
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 75 Years
Show eligibility criteria text
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
References
Publications (2)
- DERIVEDCremolini 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. PMID 32816630
- DERIVEDHurwitz 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. PMID 30552157