Clinical trial NCT04294264: TAS-102 and Oxaliplatin for the Treatment of Refractory Stage IV Colon Cancer
Official title: TAS-102 in Combination With Oxaliplatin (TAS-OX) for Refractory Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: 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
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-03-04
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Overall response rate
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression free survival
timeFrame: 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
measure: Overall survival
timeFrame: Up to 2 years
measure: Disease control rate
timeFrame: Up to 2 years
measure: Duration of response
timeFrame: Up to 2 years
measure: Incidence of adverse events
timeFrame: Up to 28 days post treatment
Other outcomes:
Locations:
city: Elizabeth
country: United States
facility: Trinitas Hospital and Comprehensive Cancer Center
state: New Jersey
city: Lakewood
country: United States
facility: RWJBarnabas Health - Monmouth Medical Center Southern Campus
state: New Jersey
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Long Branch
country: United States
facility: RWJBarnabas Health - Monmouth Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Toms River
country: United States
facility: RWJBarnabas Health - Community Medical Center
state: New Jersey
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Howard S Hochster
role: PRINCIPAL_INVESTIGATOR
References: