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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Recurrent Colon Carcinoma; Metastatic Colorectal Carcinoma; Stage IV Colon Cancer AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Refractory Colorectal Carcinoma
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Trifluridine and Tipiracil Hydrochloride

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Elizabeth, New Jersey, United States, 07202
      • Trinitas Hospital and Comprehensive Cancer Center
    • Lakewood, New Jersey, United States, 08701
      • RWJBarnabas Health - Monmouth Medical Center Southern Campus
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center
    • Long Branch, New Jersey, United States, 07740
      • RWJBarnabas Health - Monmouth Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • Toms River, New Jersey, United States, 08755
      • RWJBarnabas Health - Community Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (TAS-102, oxaliplatin); 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; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; Ai Heng; Aiheng; Diaminocyclohexane Oxalatoplatinum; Eloxatine; JM-83; Oxalatoplatin; Oxalatoplatinum; RP 54780; RP-54780; SR-96669; Drug: Trifluridine and Tipiracil Hydrochloride; Given PO; Other Names: Lonsurf; TAS-102; TAS 102; Tipiracil Hydrochloride Mixture with Trifluridine; Trifluridine/Tipiracil; Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102

What is the study measuring?

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
Overall survival		Up to 2 years
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
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

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Howard S Hochster, Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2019
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): March 31, 2024

Study Registration Dates

• First Submitted: March 2, 2020
• First Submitted That Met QC Criteria: March 2, 2020
• First Posted (Actual): March 4, 2020

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Carcinoma; Colorectal Neoplasms; Colonic Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Oxaliplatin; Trifluridine
• Other Study ID Numbers: Pro2018001469; P30CA072720 (U.S. NIH Grant/Contract); NCI-2020-00871 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 071801 (Other Identifier: Rutgers Cancer Institute of New Jersey)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No