A Phase 1b/2 Multicenter Study to Investigate the Safety, Efficacy and Proof of Concept (POC) of Nivolumab Monotherapy as a Sequential Therapy Following Preoperative Chemoradiotherapy Patients With Locally Advanced Resectable Rectal Cancer
Overview
- Phase
- Phase 1
- Intervention
- Nivolumab
- Conditions
- Cancer of Rectum
- Sponsor
- Takayuki Yoshino
- Enrollment
- 90
- Locations
- 3
- Primary Endpoint
- Pathological complete response
- Last Updated
- 4 years ago
Overview
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.
Investigators
Takayuki Yoshino
Director of Gastrointestinal Oncology Division
National Cancer Center Hospital East
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Nivolumab & Ipilimumab(Only Cohort D)
chemoradiotherapy with capecitabine+ Nivolumab + Ipilimumab(Only Cohort D) + surgical therapy
Intervention: Nivolumab
Nivolumab & Ipilimumab(Only Cohort D)
chemoradiotherapy with capecitabine+ Nivolumab + Ipilimumab(Only Cohort D) + surgical therapy
Intervention: Ipilimumab
Outcomes
Primary Outcomes
Pathological complete response
Time Frame: 1 year
Pathological complete response will be evaluated with American Joint Committee on Cancer (AJCC) Cancer Staging
Secondary Outcomes
- Rate of radical resection(1 year)
- Recurrence pattern (local or distant)(1 year)
- Disease-free survival (DFS)(5years)
- Overall survival (OS)(5years)
- Incidence of adverse events (AEs)(1 year)
- Objective response rate(1 year)
- Rate of completing the protocol therapy(1 year)
- Safety evaluation(5years)
- macroscopic evaluation of (rectal cancer) resected specimen(1 year)