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
Conditions
Brief summary
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
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.
Interventions
DRUGOxaliplatin
Given IV
Given PO
Sponsors
National Cancer Institute (NCI)
Rutgers, The State University of New Jersey
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | Up to 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | 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 | 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. |
| Overall survival | Up to 2 years | — |
| Disease control rate | Up to 2 years | — |
| Duration of response | Up to 2 years | Response rate will be calculated by dose level. Descriptive statistics will be used to analyze efficacy data using historical data as reference. |
| Incidence of adverse events | Up to 28 days post treatment | 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. |
Countries
United States
Outcome results
None listed