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

Metastatic Colorectal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04294264
• Other study ID #: Pro2018001469
• Secondary ID: NCI-2020-00871Pr
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 12, 2019
• Est. completion date: March 31, 2024

Study information

• Verified date: March 2024
• Source: Rutgers, The State University of New Jersey
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: March 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma
• Colonic Neoplasms
• Colorectal Neoplasms
• 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

Drug:
• Oxaliplatin
Given IV
• Trifluridine and Tipiracil Hydrochloride
Given PO

Locations

Country	Name	City	State
United States	Trinitas Hospital and Comprehensive Cancer Center	Elizabeth	New Jersey
United States	RWJBarnabas Health - Monmouth Medical Center Southern Campus	Lakewood	New Jersey
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	RWJBarnabas Health - Monmouth Medical Center	Long Branch	New Jersey
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	RWJBarnabas Health - Community Medical Center	Toms River	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Rutgers, The State University of New Jersey	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Overall survival		Up to 2 years
Secondary	Disease control rate		Up to 2 years
Secondary	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
Secondary	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