Liposomal Irinotecan With TAS102 and Bevacizumab for Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This study is being done to see if combining liposomal irinotecan with TAS102 and bevacizumab confers clinical benefit for patients with treatment refractory metastatic colorectal cancer.

Detailed Description
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This prospective phase II, single arm, single site trial will evaluate the efficacy of the combination of liposomal irinotecan (nal-IRI), TAS102, and bevacizumab for the treatment of patients with mismatch repair proficient, metastatic or unresectable colorectal cancer that has previously been treated with 5-fluorouracil, oxaliplatin, irinotecan and if RAS wild-type an anti-EGFR agent. A total of 25 patients will be accrued at UW Carbone Cancer Center. Subject enrollment will occur over 12 months with the total duration of the trial expected to be 3 years. Primary Objective To determine the progression free survival (PFS) of patients with metastatic colorectal cancer treated in the treatment refractory setting with liposomal irinotecan in combination with TAS102 and bevacizumab. Secondary Objectives To evaluate the objective response rate (ORR) of liposomal irinotecan in combination with bevacizumab and TAS102. To assess the safety and tolerability of these regimens in this setting. To determine the impact of the timing of irinotecan use in prior lines of therapy on the ORR and PFS observed with these nal-IRI containing treatment regimens

Official Title
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Phase II Study of Liposomal Irinotecan With TAS102 and Bevacizumab for Patients With Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Liposomal irinotecan
* Drug: TAS102
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be ≥ 18 years of age Eastern Cooperative Oncology Group (ECOG) performance must be 0 or 1. Patients must have a histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma and be metastatic or unresectable. The cancer must be mismatch repair proficient. Patients must have had prior treatment with 5-fluorouracil, oxaliplatin, irinotecan containing regimens. If RAS wild-type must have received prior anti-EGFR therapy with either cetuximab or panitumumab. If RAS wild-type and HER2 positive then must have had a prior HER2 targeted therapy. Exclusion Criteria: Uncontrolled concurrent medical illness that would not allow for the completion of the planned therapy. Patients whose cancers possess BRAF V600 mutations are excluded. Patients must stop the use of strong inducers/inhibitors of CYP3A4 at least 2 weeks before initiating therapy. Patients must not have mismatch repair deficient or microsatellite instability high cancers. Patients must not have received prior TAS102.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a nonrandomized, single arm, open-label study of the combination of liposomal irinotecan with TAS102 and bevacizumab in patients with treatment refractory metastatic colorectal cancer.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with Metastatic or Unresectable Colorectal Cancer<br>Male and females aged 18 years and older with histologically confirmed metastatic or unresectable (not amenable to curative therapy) colorectal cancer. | Drug: Liposomal irinotecan<br>* 60mg/m2 IV on days 1 and 15<br>Drug: TAS102<br>* 35mg/m2 PO BID on days 1-5 and 15-19<br>Drug: Bevacizumab<br>* 5mg/kg IV on days 1 and 15<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS is defined as the time from D1 of treatment with the study combination until the criteria for disease progression is met as defined by RECIST 1.1 criteria or death as a result of any cause. | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR will include confirmed complete response (CR) + confirmed partial response (PR) per RECIST 1.1 divided by the number of patients receiving at least one dose of proposed combination. | up to 2 years | 
| Number of Participants Experiencing Grade 3 and 4 Toxicities | Grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (version 5.0) (CTCAE v5.0) | up to 30 days post-treatment (approximately 6 months on study) | 
| Summary of Grade 3 and 4 Toxicities by Count of participants | Grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (version 5.0) (CTCAE v5.0) | up to 30 days post-treatment (approximately 6 months on study) | 
| Efficacy of irinotecan measured by PFS for patients with and without irinotecan containing regimens | PFS will be compared between those subjects who were treated in the last 4 months with an irinotecan containing regimen versus those who were not | up to 2 years |