Trials / Completed
CompletedNCT04362839
Regorafenib, Ipilimumab and Nivolumab for the Treatment of Chemotherapy Resistant Microsatellite Stable Metastatic Colorectal Cancer
A Phase I Clinical Trial of Regorafenib, Nivolumab, and Ipilimumab in Advanced Chemotherapy Resistant Metastatic MSS Colorectal Cancer
- Status
- Completed
- Phase
- Phase 1
- Study type
- Interventional
- Enrollment
- 39 (actual)
- Sponsor
- City of Hope Medical Center · Academic / Other
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
This phase I trial studies the side effects and best dose of regorafenib when given together with ipilimumab and nivolumab in treating patients with microsatellite stable colorectal cancer that has spread to other places in the body (metastatic) and remains despite chemotherapy treatment (resistant). Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving regorafenib, ipilimumab and nivolumab may slow the tumor growth and/or shrink the tumor size in patients with colorectal cancer.
Detailed description
PRIMARY OBJECTIVE: I. To determine the recommended dose level of the combination of regorafenib, nivolumab and ipilimumab in patients with advanced metastatic colorectal cancer. SECONDARY OBJECTIVES: I. Assess the objective overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. II. Estimate the duration of response, duration of stable disease (SD), progression free survival (PFS), and overall survival (OS). III. Describe the safety of this regimen as determined by frequency and severity of associated adverse events. EXPLORATORY OBJECTIVES: I. Correlate the presence of colony stimulating factor 1 receptor (CSF1R)+ macrophages, regulatory T cells (Tregs), TILs (tumor infiltrating lymphocytes) and tumor PD-L1, CTLA-4 and PD1 expression (at baseline and post treatment) on tumor biopsies with response rate. II. Characterize the systemic immune alteration through evaluation of mandatory pre and post cycle 1, and cycle 2, and at progression blood draws. OUTLINE: This is a dose-escalation study of regorafenib. Patients receive regorafenib orally (PO) once daily (QD) on days 1-21, nivolumab intravenously (IV) over 30 minutes every 2 weeks (Q2W), and ipilimumab IV over 30 minutes every 6 weeks (Q6W). Cycles repeat every 28 day for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 and 90 days, then every 3 months for up to 5 years.
Conditions
- Advanced Colon Adenocarcinoma
- Metastatic Colon Adenocarcinoma
- Metastatic Colorectal Adenocarcinoma
- Metastatic Colorectal Carcinoma
- Metastatic Rectal Adenocarcinoma
- Stage III Colon Cancer AJCC v8
- Stage III Rectal Cancer AJCC v8
- Stage IIIA Colon Cancer AJCC v8
- Stage IIIA Rectal Cancer AJCC v8
- Stage IIIB Colon Cancer AJCC v8
- Stage IIIB Rectal Cancer AJCC v8
- Stage IIIC Colon Cancer AJCC v8
- Stage IIIC Rectal Cancer AJCC v8
- Stage IV Colon Cancer AJCC v8
- Stage IV Colorectal Cancer AJCC v8
- Stage IV Rectal Cancer AJCC v8
- Stage IVA Colon Cancer AJCC v8
- Stage IVA Colorectal Cancer AJCC v8
- Stage IVA Rectal Cancer AJCC v8
- Stage IVB Colon Cancer AJCC v8
- Stage IVB Colorectal Cancer AJCC v8
- Stage IVB Rectal Cancer AJCC v8
- Stage IVC Colon Cancer AJCC v8
- Stage IVC Colorectal Cancer AJCC v8
- Stage IVC Rectal Cancer AJCC v8
Interventions
| Type | Name | Description |
|---|---|---|
| BIOLOGICAL | Ipilimumab | Given IV |
| BIOLOGICAL | Nivolumab | Given IV |
| DRUG | Regorafenib | Given PO |
Timeline
- Start date
- 2020-05-27
- Primary completion
- 2025-12-11
- Completion
- 2025-12-11
- First posted
- 2020-04-27
- Last updated
- 2026-01-28
Locations
1 site across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT04362839. Inclusion in this directory is not an endorsement.