Study of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Who Are Receiving Chemotherapy and Radiation Therapy (MK-3475-975/KEYNOTE-975)
- Conditions
- Interventions
- Registration Number
- NCT04210115
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to assess the efficacy and safety of treatment with definitive chemoradiotherapy (dCRT) + pembrolizumab (MK-3475) compared to treatment with dCRT + placebo with respect to Event-free Survival (EFS) and Overall Survival (OS) in:
...
- Detailed Description
Participants receive pembrolizumab or placebo PLUS one of two chemotherapy regimens PLUS radiation therapy for up to approximately one year. The chemotherapy regimens are either:
* FP (5-fluorouracil \[5-FU\] + cisplatin) or
* FOLFOX (5-FU + oxaliplatin + leucovorin or levoleucovorin).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 703
- Has histologically or cytologically confirmed diagnosis of CTX N+ M0 or cT2-T4a NX M0 ESCC, GEJC, EAC, or histologically or cytologically confirmed diagnosis of cTX N+ M1 cervical or upper thoracic esophageal carcinoma with supraclavicular lymph node metastases only
- Is deemed suitable for dCRT
- Is ineligible for curative surgery based on the documented opinion of a qualified medical/surgical/radiation oncologist.
- Is not expected to require tumor resection during the course of the study
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days of the first dose of study treatment
- Has adequate organ function
- Male participants must use adequate contraception (a male condom plus partner use of an additional contraceptive method) unless confirmed to be azoospermic (vasectomized or secondary to medical cause) and refrain from donating sperm during the study treatment period and through 90 days after the last dose of chemotherapy
- Female participants who are a Woman of Childbearing Potential (WOCBP) must use contraception that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle, during the study treatment period through 180 days after the last dose of chemotherapy or 120 days after the last dose of pembrolizumab, whichever is greater, and agree not to donate eggs to others or freeze/store for her own use for the purpose of reproduction during this period
- Female participants must not be pregnant or breastfeeding
- Has direct invasion of tumor into adjacent organs such as the aorta or trachea or has radiographic evidence of >90 degree encasement or invasion of a major blood vessel, or of intratumoral cavitation
- Has had major surgery other than for insertion of a feeding tube, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipates the need for major surgery during study treatment; participants with gastric or esophageal fistulae are excluded
- Has had weight loss of >20% in the previous 3 months
- Has had prior chemotherapy or radiotherapy for esophageal cancer
- Has had a myocardial infarction within the past 6 months
- Has symptomatic congestive heart failure
- Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
- Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention; administration of killed vaccines is allowed
- Has received any prior systemic anticancer therapy for esophageal cancer including investigational agents
- Has not recovered from all adverse events (AEs) due to previous non-anticancer therapies to ≤Grade 1 or Baseline
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded from the study. Participants with localized prostate cancer that has undergone potentially curative treatment can be enrolled in the study.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab, any of the study chemotherapy agents, or their excipients
- Has an active autoimmune disease that has required systemic treatment in past 2 years
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a known history of Hepatitis B or known active Hepatitis C virus infection
- Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment (180 days for participants receiving cisplatin who are breastfeeding)
- Has had an allogeneic tissue/solid organ transplant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab+FP or FOLFOX Therapy+Radiotherapy pembrolizumab Participants receive pembrolizumab 200 mg on Day 1 of each 3-week cycle for 8 cycles followed by pembrolizumab 400 mg on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-fluorouracil (5-FU)\] 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gray \[Gy\] in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by intravenous (IV) infusion. Total treatment duration is approximately 1 year. Pembrolizumab+FP or FOLFOX Therapy+Radiotherapy radiotherapy Participants receive pembrolizumab 200 mg on Day 1 of each 3-week cycle for 8 cycles followed by pembrolizumab 400 mg on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-fluorouracil (5-FU)\] 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gray \[Gy\] in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by intravenous (IV) infusion. Total treatment duration is approximately 1 year. Placebo+FP or FOLFOX Therapy+Radiotherapy placebo Participants receive placebo on Day 1 of each 3-week cycle for 8 cycles followed by placebo on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-FU 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gy in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by IV infusion. Total treatment duration is approximately 1 year. Placebo+FP or FOLFOX Therapy+Radiotherapy radiotherapy Participants receive placebo on Day 1 of each 3-week cycle for 8 cycles followed by placebo on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-FU 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gy in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by IV infusion. Total treatment duration is approximately 1 year. Pembrolizumab+FP or FOLFOX Therapy+Radiotherapy cisplatin Participants receive pembrolizumab 200 mg on Day 1 of each 3-week cycle for 8 cycles followed by pembrolizumab 400 mg on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-fluorouracil (5-FU)\] 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gray \[Gy\] in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by intravenous (IV) infusion. Total treatment duration is approximately 1 year. Pembrolizumab+FP or FOLFOX Therapy+Radiotherapy 5-FU Participants receive pembrolizumab 200 mg on Day 1 of each 3-week cycle for 8 cycles followed by pembrolizumab 400 mg on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-fluorouracil (5-FU)\] 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gray \[Gy\] in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by intravenous (IV) infusion. Total treatment duration is approximately 1 year. Pembrolizumab+FP or FOLFOX Therapy+Radiotherapy leucovorin Participants receive pembrolizumab 200 mg on Day 1 of each 3-week cycle for 8 cycles followed by pembrolizumab 400 mg on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-fluorouracil (5-FU)\] 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gray \[Gy\] in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by intravenous (IV) infusion. Total treatment duration is approximately 1 year. Pembrolizumab+FP or FOLFOX Therapy+Radiotherapy levoleucovorin Participants receive pembrolizumab 200 mg on Day 1 of each 3-week cycle for 8 cycles followed by pembrolizumab 400 mg on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-fluorouracil (5-FU)\] 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gray \[Gy\] in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by intravenous (IV) infusion. Total treatment duration is approximately 1 year. Pembrolizumab+FP or FOLFOX Therapy+Radiotherapy oxaliplatin Participants receive pembrolizumab 200 mg on Day 1 of each 3-week cycle for 8 cycles followed by pembrolizumab 400 mg on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-fluorouracil (5-FU)\] 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gray \[Gy\] in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by intravenous (IV) infusion. Total treatment duration is approximately 1 year. Placebo+FP or FOLFOX Therapy+Radiotherapy cisplatin Participants receive placebo on Day 1 of each 3-week cycle for 8 cycles followed by placebo on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-FU 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gy in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by IV infusion. Total treatment duration is approximately 1 year. Placebo+FP or FOLFOX Therapy+Radiotherapy leucovorin Participants receive placebo on Day 1 of each 3-week cycle for 8 cycles followed by placebo on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-FU 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gy in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by IV infusion. Total treatment duration is approximately 1 year. Placebo+FP or FOLFOX Therapy+Radiotherapy 5-FU Participants receive placebo on Day 1 of each 3-week cycle for 8 cycles followed by placebo on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-FU 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gy in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by IV infusion. Total treatment duration is approximately 1 year. Placebo+FP or FOLFOX Therapy+Radiotherapy levoleucovorin Participants receive placebo on Day 1 of each 3-week cycle for 8 cycles followed by placebo on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-FU 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gy in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by IV infusion. Total treatment duration is approximately 1 year. Placebo+FP or FOLFOX Therapy+Radiotherapy oxaliplatin Participants receive placebo on Day 1 of each 3-week cycle for 8 cycles followed by placebo on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-FU 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gy in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by IV infusion. Total treatment duration is approximately 1 year.
- Primary Outcome Measures
Name Time Method Event-free Survival (EFS) Up to ~60 months EFS is defined as the time from randomization to an event defined as local, regional, or distant radiological recurrence as assessed by the investigator; clinical recurrence as assessed by the investigator with histopathologic confirmation (in the absence of radiological disease recurrence by investigator assessment); or death from any cause, whichever occur...
Overall Survival (OS) Up to ~72 months OS is defined as the time from randomization to death from any cause.
- Secondary Outcome Measures
Name Time Method Number of participants with an adverse event (AE) Up to ~15 months An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Number of participants discontinuing study treatment due to an adverse event (AE) Up to ~12 months An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Trial Locations
- Locations (170)
Greater Baltimore Medical Center ( Site 0031)
🇺🇸Baltimore, Maryland, United States
Allegheny Health Network ( Site 0042)
🇺🇸Pittsburgh, Pennsylvania, United States
ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 0088)
🇧🇷Ijui, Rio Grande Do Sul, Brazil
Baguio General Hospital and Medical Center ( Site 0603)
🇵🇭Baguio City, Benguet, Philippines
Clinica de Oncologia Reichow ( Site 0085)
🇧🇷Blumenau, Santa Catarina, Brazil
Clinica San Gabriel ( Site 0142)
🇵🇪Lima, Peru
China Medical University Hospital ( Site 0646)
🇨🇳Taichung, Taiwan
Royal Free Hospital ( Site 0702)
🇬🇧London, England, United Kingdom
Hospital Nacional Arzobispo Loayza ( Site 0143)
🇵🇪Lima, Peru
Royal Marsden Hospital (Sutton) ( Site 0281)
🇬🇧Sutton, Surrey, United Kingdom
University College Hospital NHS Foundation Trust ( Site 0701)
🇬🇧London, Worcestershire, United Kingdom
CHU Amiens Picardie Site Sud Amiens ( Site 0235)
🇫🇷Amiens, Somme, France
Oncomedica ( Site 0125)
🇬🇹Guatemala, Guatemala
Chang Gung Medical Foundation. Linkou ( Site 0642)
🇨🇳Taoyuan, Taiwan
National Taiwan University Hospital ( Site 0641)
🇨🇳Taipei, Taiwan
Cebu Doctors University Hospital ( Site 0604)
🇵🇭Cebu City, Cebu, Philippines
Utah Cancer Specialists ( Site 0697)
🇺🇸Salt Lake City, Utah, United States
Centro Investigación del Cáncer James Lind ( Site 0106)
🇨🇱Temuco, Araucania, Chile
Hospital Regional de Concepcion ( Site 0105)
🇨🇱Concepcion, Biobio, Chile
Centre Francois Baclesse ( Site 0236)
🇫🇷Caen, Calvados, France
CHU Limoges Hopital Dupuytren ( Site 0225)
🇫🇷Limoges, Haute-Vienne, France
Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 0103)
🇨🇱Temuco, Araucania, Chile
CHD Vendee ( Site 0227)
🇫🇷La Roche sur Yon, Vendee, France
Centre Georges Francois Leclerc ( Site 0223)
🇫🇷Dijon, Cote-d Or, France
Centro de Cancer Nuestra Senora de la Esperanza ( Site 0104)
🇨🇱Santiago, Region M. De Santiago, Chile
SA Pohja-Eesti Regionaalhaigla ( Site 0201)
🇪🇪Tallinn, Harjumaa, Estonia
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0005)
🇨🇦Montreal, Quebec, Canada
Masarykuv onkologicky ustav-Klinika komplexni onkologicke pece ( Site 0721)
🇨🇿Brno, Brno-mesto, Czechia
Marienhospital Stuttgart Vincenz von Paul Kliniken gGmbH ( Site 0253)
🇩🇪Stuttgart, Baden-Wurttemberg, Germany
SA Tartu Ulikooli Kliinikum ( Site 0202)
🇪🇪Tartu, Tartumaa, Estonia
Institut De Cancerologie De Lorraine ( Site 0222)
🇫🇷Vandoeuvre les Nancy, Ain, France
Institut Jean Godinot ( Site 0238)
🇫🇷Reims, Marne, France
Universitaetsklinikum Muenster ( Site 0248)
🇩🇪Muenster, Nordrhein-Westfalen, Germany
Fakultni nemocnice Ostrava-Klinika onkologicka ( Site 0719)
🇨🇿Ostrava, Moravskoslezsky Kraj, Czechia
Institut Sainte Catherine ( Site 0228)
🇫🇷Avignon, Provence-Alpes-Cote-d Azur, France
Fakultni nemocnice v Motole-Onkologicka klinika 2. LF UK a FN Motol ( Site 0718)
🇨🇿Praha, Praha 5, Czechia
Medi-K Cayala ( Site 0124)
🇬🇹Guatemala, Guatemala
CENTRO HEMATO ONCOLOGICO PRIVADO-CHOP ( Site 0728)
🇲🇽Toluca de Lerdo, Mexico
Fakultni nemocnice Olomouc-Onkologicka klinika ( Site 0720)
🇨🇿Olomouc, Olomoucky Kraj, Czechia
Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 0262)
🇭🇺Gyula, Bekes, Hungary
Hospital da Luz ( Site 0373)
🇵🇹Lisboa, Portugal
Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0371)
🇵🇹Porto, Portugal
Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 0392)
🇷🇴Cluj-Napoca, Cluj, Romania
Queen Mary Hospital ( Site 0541)
🇭🇰Pokfulam, Hong Kong
Universitaetsklinikum Koeln ( Site 0251)
🇩🇪Koeln, Nordrhein-Westfalen, Germany
Asan Medical Center ( Site 0623)
🇰🇷Songpagu, Seoul, Korea, Republic of
GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 0430)
🇷🇺Ufa, Baskortostan, Respublika, Russian Federation
Grupo Medico Angeles ( Site 0121)
🇬🇹Guatemala, Guatemala
Pecsi Tudomanyegyetem AOK ( Site 0265)
🇭🇺Pecs, Baranya, Hungary
Hospital Beatriz Angelo ( Site 0374)
🇵🇹Loures, Lisboa, Portugal
Ovidius Clinical Hospital OCH-Oncology and Hematology ( Site 0393)
🇷🇴Ovidiu, Constanta, Romania
Chonnam National University Hwasun Hospital ( Site 0625)
🇰🇷Hwasun Gun, Jeonranamdo, Korea, Republic of
Debreceni Egyetem Klinikai Kozpont ( Site 0261)
🇭🇺Debrecen, Hungary
Cryptex Investigación Clínica S.A. de C.V. ( Site 0729)
🇲🇽Cuauhtémoc, Ciudad De México, Distrito Federal, Mexico
S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 0394)
🇷🇴Craiova, Dolj, Romania
Chang Gung Med Foundation. Kaohsiung Branch ( Site 0643)
🇨🇳Kaohsiung, Taiwan
Azienda Ospedaliero Universitaria Pisana - Presidio Santa Chiara ( Site 0294)
🇮🇹Pisa, Toscana, Italy
Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 0451)
🇹🇷Istanbul, Turkey
National Cancer Center ( Site 0626)
🇰🇷Goyang-si, Kyonggi-do, Korea, Republic of
National Cancer Center Hospital East ( Site 0562)
🇯🇵Kashiwa, Chiba, Japan
Kaluga Regional Clinical Oncology Center ( Site 0424)
🇷🇺Kaluga, Kaluzskaja Oblast, Russian Federation
Gastrosoluciones ( Site 0126)
🇬🇹Guatemala, Guatemala
Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE ( Site 0372)
🇵🇹Lisboa, Portugal
CHLN Hospital Santa Maria ( Site 0376)
🇵🇹Lisboa, Portugal
MedEuropa Bucuresti - Centru de Radioterapie-Oncology ( Site 0400)
🇷🇴București, Bucuresti, Romania
S.C.Focus Lab Plus S.R.L ( Site 0395)
🇷🇴Bucuresti, Romania
Taichung Veterans General Hospital-Radiation Oncology ( Site 0647)
🇨🇳Taichung, Taiwan
Orszagos Onkologiai Intezet ( Site 0263)
🇭🇺Budapest, Hungary
Samsung Medical Center ( Site 0622)
🇰🇷Seoul, Korea, Republic of
Istanbul University Cerrahpasa Medical Faculty ( Site 0452)
🇹🇷Istambul, Istanbul, Turkey
Saitama Cancer Center ( Site 0564)
🇯🇵Kitaadachi-gun, Saitama, Japan
Shizuoka Cancer Center Hospital and Research Institute ( Site 0566)
🇯🇵Sunto-gun, Shizuoka, Japan
SBHI Samara Regional Clinical Oncology Dispensary ( Site 0420)
🇷🇺Samara, Samarskaya Oblast, Russian Federation
National Cheng Kung University Hospital ( Site 0645)
🇨🇳Tainan, Taiwan
The Medical City-Iloilo ( Site 0602)
🇵🇭Iloilo City, Iloilo, Philippines
S.C. Radiotherapy Center Cluj S.R.L ( Site 0391)
🇷🇴Cluj-Napoca, Cluj, Romania
Centrul Medical Topmed ( Site 0398)
🇷🇴Targu-Mures, Mures, Romania
Cambridge University Hospitals NHS Trust ( Site 0477)
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Main Military Clinical Hospital n.a. N.N.Burdenko ( Site 0421)
🇷🇺Moscow, Moskva, Russian Federation
Anhui Provincial Hospital-Oncology Radiotherapy Department ( Site 0531)
🇨🇳Hefei, Anhui, China
Shanghai Chest Hospital ( Site 0503)
🇨🇳Shangai, Shanghai, China
Sichuan Cancer Hospital ( Site 0527)
🇨🇳Chengdu, Sichuan, China
Tianjin Medical University Cancer Institute & Hospital ( Site 0505)
🇨🇳Tianjin, Tianjin, China
The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Si
🇨🇳Fuzhou, Fujian, China
The First Affiliated Hospital of Xiamen University ( Site 0538)
🇨🇳Xiamen, Fujian, China
Hunan Cancer Hospital ( Site 0515)
🇨🇳Changsha, Hunan, China
Huai an First People s Hospital ( Site 0526)
🇨🇳Huai An, Jiangsu, China
Jiangxi Cancer Hospital ( Site 0512)
🇨🇳Nanchang, Jiangxi, China
Hubei Cancer Hospital ( Site 0514)
🇨🇳Wuhan, Hubei, China
The Affiliated Hospital of Xuzhou Medical University ( Site 0522)
🇨🇳Xuzhou, Jiangsu, China
Affiliated Hospital of Jiangsu University ( Site 0524)
🇨🇳Zhenjiang, Jiangsu, China
Jiangsu Cancer Hospital ( Site 0519)
🇨🇳Nanjing, Jiangsu, China
Shanghai Chest Hospital ( Site 0501)
🇨🇳Shanghai, Shanghai, China
Zhongshan Hospital Fudan University ( Site 0502)
🇨🇳Shanghai, Shanghai, China
Zhejiang Cancer Hospital ( Site 0529)
🇨🇳Hangzhou, Zhejiang, China
Hangzhou First People's Hospital ( Site 0530)
🇨🇳Hangzhou, Zhejiang, China
Sir Run Run Shaw Hospital ( Site 0523)
🇨🇳Hangzhou, Zhejiang, China
Rigshospitalet ( Site 0199)
🇩🇰Copenhagen, Hovedstaden, Denmark
Odense Universitetshospital ( Site 0200)
🇩🇰Odense, Syddanmark, Denmark
Fondazione IRCCS Policlinico San Matteo-Oncology ( Site 0300)
🇮🇹Pavia, Lombardia, Italy
ASST Papa Giovanni XXIII ( Site 0296)
🇮🇹Bergamo, Italy
Azienda Socio Sanitaria Territoriale di Cremona ( Site 0299)
🇮🇹Cremona, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0292)
🇮🇹Milano, Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale-SC Oncologia Clinica Sperimentale Addome ( Site 0
🇮🇹Napoli, Italy
IRCCS Istituto Oncologico Veneto ( Site 0298)
🇮🇹Padova, Italy
Policlinico Universitario A. Gemelli ( Site 0297)
🇮🇹Roma, Italy
Sunnybrook Research Institute ( Site 0012)
🇨🇦Toronto, Ontario, Canada
Cross Cancer Institute ( Site 0010)
🇨🇦Edmonton, Alberta, Canada
The Ottawa Hospital - Cancer Care ( Site 0008)
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Centre ( Site 0011)
🇨🇦Toronto, Ontario, Canada
Mount Vernon Hospital ( Site 0478)
🇬🇧Northwood, United Kingdom
Medical institute named after Berezin Sergey ( Site 0417)
🇷🇺St. Petersburg, Sankt-Peterburg, Russian Federation
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0412)
🇷🇺Kazan, Tatarstan, Respublika, Russian Federation
FSAI Treatment and Rehabilitation Centre of the MoH and SD of RF ( Site 0429)
🇷🇺Moscow, Moskva, Russian Federation
University of Missouri ( Site 0688)
🇺🇸Columbia, Missouri, United States
MemorialCare Health System - Long Beach Medical Center-Oncology ( Site 0691)
🇺🇸Long Beach, California, United States
University of Kansas Cancer Center ( Site 0023)
🇺🇸Westwood, Kansas, United States
University Medical Center ( Site 0035)
🇺🇸New Orleans, Louisiana, United States
Cancer Center of Kansas ( Site 0058)
🇺🇸Wichita, Kansas, United States
Dana Farber Cancer Center ( Site 0034)
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital ( Site 0685)
🇺🇸Detroit, Michigan, United States
Stephenson Cancer Center ( Site 0044)
🇺🇸Oklahoma City, Oklahoma, United States
Rutgers Cancer Institute of New Jersey ( Site 0695)
🇺🇸New Brunswick, New Jersey, United States
Renown Regional Medical Center ( Site 0706)
🇺🇸Reno, Nevada, United States
Oregon Health & Science University Center for Health & Healing 2- CHH2 ( Site 0060)
🇺🇸Portland, Oregon, United States
Weill Cornell Medical College ( Site 0053)
🇺🇸New York, New York, United States
Cancer Care Northwest - Spokane Valley ( Site 0036)
🇺🇸Spokane Valley, Washington, United States
University of Wisconsin Hospital and Clinics ( Site 0033)
🇺🇸Madison, Wisconsin, United States
Instituto Medico Alexander Fleming ( Site 0063)
🇦🇷Buenos Aires, Caba, Argentina
Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo ( Site 0066)
🇦🇷Buenos Aires, Argentina
Fundacion Favaloro ( Site 0061)
🇦🇷Ciudad de Buenos Aires, Caba, Argentina
UZ Leuven ( Site 0161)
🇧🇪Leuven, Vlaams-Brabant, Belgium
UZ Gent ( Site 0163)
🇧🇪Gent, Oost-Vlaanderen, Belgium
CEMIC ( Site 0064)
🇦🇷Buenos Aires, Argentina
UCL Saint Luc ( Site 0162)
🇧🇪Brussels, Bruxelles-Capitale, Region De, Belgium
AZ Delta ( Site 0165)
🇧🇪Roeselare, West-Vlaanderen, Belgium
Hospital Nossa Senhora da Conceicao ( Site 0087)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0081)
🇧🇷Sao Paulo, Brazil
CancerCare Manitoba ( Site 0002)
🇨🇦Winnipeg, Manitoba, Canada
Institut Curie - Centre Rene Huguenin ( Site 0237)
🇫🇷Saint-Cloud, Hauts-de-Seine, France
CHU Hotel Dieu Nantes ( Site 0230)
🇫🇷Nantes, Pays-de-la-Loire, France
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz ( Site 0247)
🇩🇪Mainz, Rheinland-Pfalz, Germany
Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 0122)
🇬🇹Guatemala, Guatemala
Centro Medico Integral De Cancerología (CEMIC) ( Site 0123)
🇬🇹Quetzaltenango, Guatemala
IRCCS Policlinico San Donato ( Site 0295)
🇮🇹San Donato Milanese, Milano, Italy
National Cancer Center Hospital ( Site 0561)
🇯🇵Tokyo, Japan
Severance Hospital Yonsei University Health System ( Site 0624)
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital ( Site 0621)
🇰🇷Seoul, Korea, Republic of
Instituto Nacional de Enfermedades Neoplasicas ( Site 0141)
🇵🇪Lima, Muni Metro De Lima, Peru
Detecta Clínica ( Site 0146)
🇵🇪Surquillo, Muni Metro De Lima, Peru
St. Luke s Medical Center ( Site 0601)
🇵🇭Quezon, National Capital Region, Philippines
Pavlov First Saint Petersburg State Medical University ( Site 0426)
🇷🇺St. Petersburg, Sankt-Peterburg, Russian Federation
Memorial Ankara Hastanesi ( Site 0461)
🇹🇷Ankara, Turkey
Izmir Katip Celebi Universitesi Ataturk Egitim ve Arastirma Hastanesi ( Site 0458)
🇹🇷Izmir, Turkey
Ege Universitesi Tip Fakultesi ( Site 0457)
🇹🇷Izmir, Turkey
Aberdeen Royal Infirmary ( Site 0474)
🇬🇧Aberdeen, Aberdeen City, United Kingdom
Hammersmith Hospital-Medical Oncology ( Site 0471)
🇬🇧London, London, City Of, United Kingdom
ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 0283)
🇬🇧London, London, City Of, United Kingdom
Nottingham University Hospitals NHS Trust ( Site 0476)
🇬🇧Nottingham, Nottinghamshire, United Kingdom
The Christie NHS Foundation Trust ( Site 0282)
🇬🇧Manchester, United Kingdom
Facharztzentrum Eppendorf ( Site 0242)
🇩🇪Hamburg, Germany
Kanagawa Cancer Center ( Site 0565)
🇯🇵Yokohama, Kanagawa, Japan
Columbus Regional Research Institute ( Site 0047)
🇺🇸Columbus, Georgia, United States
Sverdlovsk Regional Oncology Hospital ( Site 0411)
🇷🇺Ekaterinburg, Sverdlovskaya Oblast, Russian Federation
Charite Campus Virchow Klinikum ( Site 0250)
🇩🇪Berlin, Germany
Thompson Cancer Survival Center ( Site 0696)
🇺🇸Knoxville, Tennessee, United States
Aichi Cancer Center Hospital ( Site 0563)
🇯🇵Nagoya, Aichi, Japan
Koo Foundation Sun Yat-Sen Cancer Center ( Site 0644)
🇨🇳Taipei, Taiwan
Princess Margaret Hospital. ( Site 0542)
🇭🇰Hong Kong, Hong Kong
Pamela Youde Nethersole Eastern Hospital ( Site 0543)
🇭🇰Hong Kong, Hong Kong