TAS-102 and Oxaliplatin for the Treatment of Refractory Stage IV Colon Cancer

Study Overview
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Brief Summary
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This phase II trial studies how well TAS-102 and oxaliplatin work in treating patients with stage IV colon cancer. Drugs used in chemotherapy, such as TAS-102 and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed Description
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PRIMARY OBJECTIVE: I. Overall response rate (ORR). SECONDARY OBJECTIVES: I. Progression free survival (PFS). II. Overall survival (OS). III. Disease control rate (DCR). IV. Duration of response. V. Safety and tolerability. OUTLINE: Patients receive trifluridine and tipiracil hydrochloride (TAS-102) orally (PO) twice daily (BID) on days 1-5 and oxaliplatin intravenously (IV) over 2 hours on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 28 days.

Official Title
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TAS-102 in Combination With Oxaliplatin (TAS-OX) for Refractory Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Carcinoma, Recurrent Colon Carcinoma, Refractory Colorectal Carcinoma, Stage IV Colon Cancer AJCC v7, Stage IVA Colon Cancer AJCC v7, Stage IVB Colon Cancer AJCC v7

Intervention / Treatment
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* Drug: Oxaliplatin
* Drug: Trifluridine and Tipiracil Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed stage IV colon cancer (American Joint Committee on Cancer [AJCC] 7th edition) that has progressed after standard therapy that included fluorouracil (5-FU), irinotecan, oxaliplatin, bevacizumab (unless contraindicated) and an anti-EGFR antibody, if RAS wild type. Patients who could not tolerate standard agents because of unacceptable, but reversible toxicity necessitating their discontinuation will be allowed to participate Patients who had received adjuvant chemotherapy and had recurrence during or within 6 months of completion of the adjuvant chemotherapy will be allowed to count the adjuvant therapy as one chemotherapy regimen Progression of disease must be documented on the most recent scan Presence of measurable disease RAS mutation and mismatch repair deficiency (MMR) status must be determined (or tissue availability for testing if not already determined) Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Life expectancy of at least 3 months Absolute neutrophil count (ANC) >= 1.5 x 10^9/L Hemoglobin >= 9 g/dL Platelets (PLT) >= 75 x 10^9/L Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 5 x upper limit of normal (ULN) Adequate contraception if applicable Women who are nursing and discontinue nursing prior to enrollment in the program Ability to take oral medication (i.e., no feeding tube) Patient able and willing to comply with study procedures as per protocol Patient able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures Exclusion Criteria: Patients who have previously received TAS-102 Grade 2 or higher peripheral neuropathy (functional impairment) Symptomatic central nervous system (CNS) metastases requiring treatment Other active malignancy within the last 3 years (except for non-melanoma skin cancer or a non-invasive/in situ cancer) Pregnancy or breast feeding Current therapy with other investigational agents Active infection with body temperature >= 38 degree Celsius (C) due to infection Major surgery within prior 4 weeks (the surgical incision should be fully healed prior to drug administration) Any anticancer therapy within prior 3 weeks of first dose of study drug History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102 Current therapy with other investigational agents or participation in another clinical study or any investigational agent received within prior 4 weeks Grade 3 or higher hypersensitivity reaction to oxaliplatin, or grade 1-2 hypersensitivity reaction to oxaliplatin not controlled with pre-medication Has unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse (CTCAE) grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum-induced neurotoxicity)

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (TAS-102, oxaliplatin)<br>Patients receive TAS-102 PO BID on days 1-5 and oxaliplatin IV over 2 hours on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. | Drug: Oxaliplatin<br>* Given IV<br>* Other names: SR-96669;Drug: Trifluridine and Tipiracil Hydrochloride<br>* Given PO<br>* Other names: Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Response rate is defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR) by investigator assessment as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1. Response rate will be calculated by dose level. Descriptive statistics will be used to analyze efficacy data using historical data as reference. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Progression will be assessed by a computed tomography CT scan according to RECIST criteria version 1.1. This criterion will be estimated by the Kaplan-Meier method. Patients who have not progressed or died at the time of analysis will be censored at the time of their latest follow-up with clinically stable disease. | From the date of start of treatment to the date of first documented progression or any cause of death during the study, assessed up to 2 years | 
| Overall survival |  | Up to 2 years | 
| Disease control rate |  | Up to 2 years | 
| Duration of response | Response rate will be calculated by dose level. Descriptive statistics will be used to analyze efficacy data using historical data as reference. | Up to 2 years | 
| Incidence of adverse events | All recorded adverse events will be listed and tabulated by system organ class and dose level. Will utilize the Cancer Therapy Evaluation Program Common Toxicity Criteria (CTC) version 5.0 for toxicity and adverse event reporting. | Up to 28 days post treatment |