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

Phase 2
Recruiting
Conditions
Metastatic Colorectal Cancer
Interventions
Registration Number
NCT05854498
Lead Sponsor
University of Wisconsin, Madison
Brief Summary

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

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

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
25
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Participants with Metastatic or Unresectable Colorectal CancerLiposomal irinotecanMale and females aged 18 years and older with histologically confirmed metastatic or unresectable (not amenable to curative therapy) colorectal cancer.
Participants with Metastatic or Unresectable Colorectal CancerTAS102Male and females aged 18 years and older with histologically confirmed metastatic or unresectable (not amenable to curative therapy) colorectal cancer.
Participants with Metastatic or Unresectable Colorectal CancerBevacizumabMale and females aged 18 years and older with histologically confirmed metastatic or unresectable (not amenable to curative therapy) colorectal cancer.
Primary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS)up to 2 years

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.

Secondary Outcome Measures
NameTimeMethod
Summary of Grade 3 and 4 Toxicities by Count of participantsup to 30 days post-treatment (approximately 6 months on study)

Grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (version 5.0) (CTCAE v5.0)

Number of Participants Experiencing Grade 3 and 4 Toxicitiesup to 30 days post-treatment (approximately 6 months on study)

Grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (version 5.0) (CTCAE v5.0)

Objective Response Rate (ORR)up to 2 years

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.

Efficacy of irinotecan measured by PFS for patients with and without irinotecan containing regimensup to 2 years

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

Trial Locations

Locations (1)

University of Wisconsin Carbone Cancer Center

🇺🇸

Madison, Wisconsin, United States

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