Liposomal Irinotecan with TAS102 and Bevacizumab for the Treatment of Patients with Metastatic or Unresectable Colorectal Cancer

Inclusion Criteria

• Ability to understand and the willingness to sign a written informed consent document
• Patients must have histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma that is metastatic or unresectable
• The cancer must be mismatch repair proficient or microsatellite stable
• Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• Subjects 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 known to be HER2 amplified (defined by a next generation sequencing [NGS] copy number greater than 10 or immunohistochemistry 3+) then must have had a prior HER2 targeted therapy. Exposure to these agents can have happened in any disease setting (neoadjuvant, adjuvant, or for metastatic disease)
• Individuals at least 18 years of age. Because no dosing or adverse event data are currently available on the use of liposomal irinotecan in combination with TAS-102 and bevacizumab in patients < 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1
• Absolute neutrophil count (ANC) ≥ 1,500/mcL (obtained within 28 days of registration)
• Hemoglobin (Hgb) ≥ 8 g/dL, independent of transfusion (obtained within 28 days of registration)
• Platelets > 75,000/mcL (obtained within 28 days of registration)
• Creatinine < 2.0 mg/dL or Cockcroft-Gault calculated creatinine clearance ≥ 30 mL/min (obtained within 28 days of registration)
• Total bilirubin ≤ institutional upper limit of normal (ULN) (obtained within 28 days of registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 5 x ULN (obtained within 28 days of registration)
• Urine protein < 100 mg/dL (obtained within 28 days of registration)
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Baseline blood pressure must be less than 160/90 at baseline
• Individuals of childbearing potential must have a negative urine or serum pregnancy test up to 14 days prior to study registration. A negative pregnancy test is required within 7 days of cycle 1 day 1 (C1D1). Screening pregnancy test may be used if completed within 7 days of C1D1. A person of childbearing potential is anyone (regardless of sexual orientation, gender identity, having undergone a tubal ligation, or remaining celibate by choice) who was born with a uterus and at least one ovary and meets both of the following criteria: * Is post-menarcheal (i.e., has had at least one prior menses) * Has not undergone a hysterectomy or bilateral oophorectomy or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• Individuals in sexual relationships that could result in pregnancy or impregnation of their partner must use an acceptable method of contraception prior to enrollment until 4 weeks after completing study treatment, for people who can impregnate their partners, or 7 months after last dose if subject is of child-bearing capacity. * Note: Includes, but is not limited to, barrier with additional spermicidal foam or jelly, intrauterine device, hormonal contraception (started at least 30 days prior to study enrollment), intercourse with individual who underwent vasectomy
• Willing to comply with all study procedures and be available for the duration of the study
• Patients much be able to take oral medication

Exclusion Criteria

• Uncontrolled concurrent medical illness that would not allow for the completion of the planned therapy
• Treatment with any anti-cancer therapy or radiation within 2 weeks prior to C1D1. Subjects must be at least 6 weeks out from surgical procedures (to minimize risks associated with bevacizumab). For minor surgical procedures (i.e. venous access placement or non-surgical biopsy) there must be a minimum of at least 2 weeks between procedure and C1D1
• Subjects must not have uncontrolled central nervous system (CNS) disease. This is defined as untreated brain metastases or any leptomeningeal disease regardless of whether radiation was administered
• Subjects whose cancers possess BRAF V600 mutations
• Prior treatment with TAS-102 is not allowed. Prior irinotecan and/or bevacizumab is allowed assuming they did not have severe reactions/toxicities that would prevent these agents from being administered further
• Subjects must stop the use of strong inducers/inhibitors of CYP3A4 at least 2 weeks before initiating therapy
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Subjects must not have ascites or pleural effusions requiring paracentesis or thoracentesis in the 60 days prior to C1D1
• A person who is pregnant, lactating or planning on becoming pregnant during the study
• Concomitant malignancy that would limit the subject’s survival or require systemic therapy beyond hormonal agents
• Active infection requiring systemic therapy
• Current therapy with other investigations agents or participation in another clinical study (supportive care and nontherapeutic trial participation is allowed if not receiving an investigational drug). Subjects may participate in prescreening for other therapeutic trials (prescreening of biologic sample for specific mutations, receptors, etc.)