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

Description
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.

Objective
Primary: 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:
-To evaluate the objective response rate (ORR) of liposomal irinotecan in combination and 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 liposomal containing treatment regimens.

Treatment Drug: Liposomal irinotecan
Drug: TAS102
Drug: Bevacizumab

Key Eligibility 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.

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.

Applicable Disease Sites
Colon and Rectum

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital