A Pilot Feasibility Study of Durvalumab (MEDI4736) and Tremelimumab Following Radioembolization in Patients With Metastatic Microsatellite Stable (MSS) Colorectal Cancer to the Liver
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Metastatic Carcinoma in the Liver
- Sponsor
- City of Hope Medical Center
- Enrollment
- 9
- Locations
- 1
- Primary Endpoint
- Hepatic tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This pilot clinical trial studies the side effects and how well durvalumab and tremelimumab work in treating patients with microsatellite stable colorectal cancer that has spread to the liver. Monoclonal antibodies, such as durvalumab and tremelimumab, may interfere with the ability of tumor cells to grow and spread.
Detailed Description
PRIMARY OBJECTIVES: I. Establish the safety of durvalumab and tremelimumab following radioembolization with selective internal radiation (SIR)-Spheres in patients with microsatellite stable (MSS) metastatic colorectal cancer to the liver. II. Determine the hepatic response rate of SIR-Spheres followed by durvalumab and tremelimumab in patients with MSS metastatic colorectal cancer to the liver. SECONDARY OBJECTIVES: I. Estimate the progression free survival (PFS) and overall survival (OS) of the overall treated population. II. Describe the overall response rate of the treated population. III. Describe the extra-hepatic response in the treated population (abscopal responses). TERTIARY OBJECTIVES: I. Describe intra-tumor immune alterations following SIR-Spheres, and following durvalumab plus tremelimumab in comparison to baseline through serial hepatic metastases biopsies. II. Describe the immune alterations in the blood following SIR-Spheres and following durvalumab plus tremelimumab. OUTLINE: Patients receive durvalumab intravenously (IV) over 60 minutes and tremelimumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Beginning at week 17, patients receive durvalumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Documented informed consent of the subject and/or legally authorized representative
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy of \> 12 weeks
- •Hemoglobin \>= 9.0 g/dL
- •Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (\>= 1500 per mm\^3)
- •Platelet count \>= 75 x 10\^9/L (\>= 75,000 per mm\^3)
- •Serum bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional upper limit of normal given that all patients have liver metastases
- •Serum creatinine clearance (CL) \> 40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
- •Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: \>= 60 years old and no menses for \>= 1 year without an alternative medical cause; AND/OR history of hysterectomy, AND/OR history of bilateral tubal ligation, AND/OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry
Exclusion Criteria
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) or previous enrollment in the present study
- •Participation in another clinical study with an investigational product during the last 4 weeks
- •Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
- •History of another primary malignancy except for:
- •Malignancy treated with curative intent and with no known active disease \>= 2 years before the first dose of study drug and of low potential risk for recurrence
- •Adequately treated non-melanoma skin cancer or lentigo maligns without evidence of disease
- •Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ
- •Receipt of the last dose of chemotherapy or tyrosine kinase inhibitors should be at least 3 weeks prior to durvalumab and tremelimumab dosing; monoclonal antibodies such as bevacizumab, ziv-aflibercept, ramucirumab, cetuximab, and panitumumab should be at least 6 weeks prior to durvalumab and tremelimumab therapy
- •Clinical ascites
- •Liver involvement by \> 50% with metastatic disease determined by the investigator
Outcomes
Primary Outcomes
Hepatic tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame: Up to 1 year
Will be summarized using a 90% exact Clopper-Pearson confidence interval
Incidence of adverse events assessed by NCI CTCAE version 4.03
Time Frame: Up to 1 year
Toxicities observed will be summarized in terms of type and severity.
Secondary Outcomes
- Extrahepatic disease response assessed by RECIST 1.1(Up to 1 year)
- Hepatic PFS(From study treatment to first progression in the treated liver or death (whichever occurs first), assessed up to 1 year)
- OS(From study treatment to death, assessed up to 1 year)
- Overall PFS(From study treatment to progressive disease (hepatic and extrahepatic) and death, assessed up to 1 year)
- Overall response rate (both hepatic and extrahepatic disease) assessed by RECIST 1.1(Up to 1 year)