This phase I trial studies the side effects and how well tremelimumab and durvalumab work in treating patients with colorectal cancer that has spread to the liver and can be removed by surgery. Immunotherapy with monoclonal antibodies, such as tremelimumab and durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
PRIMARY OBJECTIVES: I. Assess the safety and feasibility of adding tremelimumab 75 mg intravenously (IV) plus durvalumab (MEDI4736) 1500 mg administered once pre-operatively and 4 cycles of durvalumab 1500 mg IV every 4 weeks for 4 cycles post-operatively in patients who are candidates for resection for colorectal cancer liver metastases. SECONDARY OBJECTIVES: I. Explore the changes in various immune parameters, including programmed cell death-1 ligand 1 (PD-L1) and programmed cell death1 (PD-1) expression in the tumor, over treatment and correlate with response and survival with goal of biomarker discovery. II. Estimate the relapse-free survival (RFS) in all enrolled subjects. OUTLINE: Patients receive tremelimumab IV over 1 hour and durvalumab IV over 4 hours during week 11. Between weeks 15 and 17, patients undergo liver surgery. Patients then receive durvalumab IV over 1 hour during weeks 21, 25, 29, and 33. After completion of study treatment, patients are followed up twice a year for 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Given IV
Correlative studies
Undergo liver surgery
Given IV
M D Anderson Cancer Center
Houston, Texas, United States
Post-operative Toxicity
Post-operative toxicity graded by the Clavien-Dindo classification. The Clavien Dindo Classification is used to rank the severity of a surgical complication. It is based on the type of therapy needed to correct the complication. The scale consists of several grades (Grade I, II, IIIa, IIIb, IVa, IVb and V). Grade I complications are usually mild but Grade II and higher complications are more significant.
Time frame: 3 years
Feasibility and Safety in the Conduct of the Trial
Feasibility and safety assessed by the rate of on-trial surgical resection of liver metastases, post-operative toxicity graded by the Clavien-Dindo classification, and treatment related toxicity graded by CTCAE v5. The combination was defined as feasible if at least 80% of participants could undergo resection or if between 60% and 80% could undergo resection with a positive toxicity and efficacy profile.
Time frame: 3 years
Treatment Related Toxicity
Treatment related toxicity graded by CTCAE v5
Time frame: 3 years
Pre-operative Response Rate
Pre-operative response rate evaluation using RECIST v1.1. RECIST 1.1 will be used to identify measurable disease on baseline CT scans. Tumor measurements will be made upon restaging CT scans prior to surgery. No tumor measurements will take place post-operatively as the goal of therapy is no evidence of disease. Pre-surgery response will be classified into Complete Response, Partial Response, Stable Disease and Progressive Disease.
Time frame: 2 years
Relapse-Free Survival (RFS)
The time from date of curative surgery to the time of recurrence or death
Time frame: 3 years
Overall Survival
The time from treatment to death, regardless of disease recurrence.
Time frame: 3 years
Translational Evaluation of Various Immune-relevant Factors
Tumor immune markers was evaluated using flow cytometry, Multiplex Immunofluorescence (mIF) and Immunohistochemistry (IHC) analyses, RNA sequencing, Microbial DNA isolation and 16S rRNA gene sequencing (using QIAamp DNA stool mini kit on pretreatment feacal samples)
Time frame: 3 years
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