Study to Nivolumab Following Preoperative Chemoradiotherapy
- Registration Number
- NCT02948348
- Lead Sponsor
- Takayuki Yoshino
- Brief Summary
This is a phase Ib/II, open-label, single-arm, multicenter study to investigate the safety, efficacy, and proof of concept (POC) of monotherapy with nivolumab, an anti-PD-1 antibody drug, as a sequential therapy following chemoradiotherapy (CRT) with capecitabine and subsequent surgical therapy in patients with locally advanced resectable rectal cancer.
- Detailed Description
\[Phase Ib\]
After preoperative CRT, to sequentially administer nivolumab in combination for patients with locally advanced resectable rectal cancer. To evaluate the safety of nivolumab in sequential combination therapy, the onset of dose-limiting toxicity (DLT) and the safety of subsequent surgical therapy, and to decide on a recommended dose (RD) for the phase II part.
\[Phase II\] PhaseⅡ is composed of 4 cohorts.
Cohort A: First-onset rectal cancer cohort (42 cases) To evaluate the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered following preoperative CRT.
And to search for biomarkers related to therapeutic effects in first-onset cases. Evaluate the safety of surgical treatment.
Cohort B: Rectal cancer with localized recurrence cohort (10 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered after preoperative CRT.
Search for biomarkers related to therapeutic effects in localized recurrence cases. Conduct an exploratory evaluation on the safety of surgical treatment.
Cohort C: Rectal cancer with resectable lung/liver metastasis cohort (10 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered after preoperative CRT.
Search for biomarkers related to therapeutic effects in resectable lung/liver metastasis cases. Conduct an exploratory evaluation on the safety of surgical treatment.
Cohort D: First-onset rectal cancer using ipilimumab-nivolumab combination cohort (25 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (240 mg/body at two-week intervals) and ipilimumab (1 mg/kg at six-week intervals) after preoperative CRT, and search for biomarkers related to therapeutic effects in first-onset cases. Conduct an exploratory evaluation on the safety of surgical treatment.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 90
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nivolumab & Ipilimumab(Only Cohort D) Nivolumab chemoradiotherapy with capecitabine+ Nivolumab + Ipilimumab(Only Cohort D) + surgical therapy Nivolumab & Ipilimumab(Only Cohort D) Ipilimumab chemoradiotherapy with capecitabine+ Nivolumab + Ipilimumab(Only Cohort D) + surgical therapy
- Primary Outcome Measures
Name Time Method Pathological complete response 1 year Pathological complete response will be evaluated with American Joint Committee on Cancer (AJCC) Cancer Staging
- Secondary Outcome Measures
Name Time Method Rate of radical resection 1 year Recurrence pattern (local or distant) 1 year Disease-free survival (DFS) 5years Evaluation Criteria In Solid Tumors (RECIST)
Overall survival (OS) 5years Evaluation Criteria In Solid Tumors (RECIST)
Incidence of adverse events (AEs) 1 year Safety will be evaluated with CTCAE v4.0
Objective response rate 1 year Evaluation Criteria In Solid Tumors (RECIST)
Rate of completing the protocol therapy 1 year Safety evaluation 5years Safety will be evaluated with CTCAE v4.0
macroscopic evaluation of (rectal cancer) resected specimen 1 year
Trial Locations
- Locations (3)
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Hokkaido University
🇯🇵Sapporo, Hokkaido, Japan
Osaka National Hospital
🇯🇵Osaka, Japan