Metastatic Colorectal Cancer
Conditions
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
Interventions
DRUGLiposomal irinotecan
50mg/m2 IV on days 1 and 15
DRUGTAS102
35mg/m2 PO BID on days 1-5 and 15-19
DRUGBevacizumab
5mg/kg IV on days 1 and 15
Sponsors
University of Wisconsin, Madison
Ipsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Number of Participants Experiencing Grade 3 and 4 Toxicities | up 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) |
| Summary of Grade 3 and 4 Toxicities by Count of participants | up 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) |
| Efficacy of irinotecan measured by PFS for patients with and without irinotecan containing regimens | up 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 |
Countries
United States
Contacts
CONTACTCancer Connect
PRINCIPAL_INVESTIGATORDustin Deming, MD
UW Carbone Cancer Center
Outcome results
None listed