A Study of Trifluridine/Tipiracil in Triple Negative Metastatic Breast Cancer

NCT ID: NCT04149444

Last Updated: 2020-06-11

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-29
• Study Completion Date: 2020-06-09

Brief Summary

This is an open-label, single arm, multi-stage, phase II trial of Trifluridine/tipiracil as a palliative treatment for patients with metastatic triple negative breast cancer who have failed both a taxane and anthracycline or have contraindications to these agents.

Detailed Description

This is an open-label, single arm, multi-stage, phase II trial of Trifluridine/tipiracil (TAS-102) as a palliative treatment for patients with metastatic triple negative breast cancer who have failed both a taxane and anthracycline or have contraindications to these agents.

The trial will begin with a safety run-in of 10 patients treated as follows:

Cycle 1: Trifluridine/tipiracil administered at 30 mg/m2 orally bid, 5 days per week, with 2 days of rest, for 2 weeks, followed by 14 day rest. Intra-patient dose escalation to 35 mg/m2 orally bid, 5 days per week, with 2 days of rest, for 2 weeks, followed by 14 day rest for subsequent cycles in the absence of dose limiting toxicities. As long as at least 80% of patients tolerate dose escalation, the trial will proceed to the next stage.

Patients enrolled in stages I and II will start Trifluridine/tipiracil at 35 mg/m2 orally bid, 5 days per week, with 2 days of rest, for 2 weeks, followed by 14 day rest.

Conditions

Metastatic Triple Negative Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ARM 1

Dose escalation cohort - First 10 patients enrolled on study.

Trifluridine/Tipiracil 30mg/m2 - to start, if no significant dose limiting side effects the dose will be increased to 35mg/m2 for the duration of the trial.

After first 10 patients enrolled on study - Trifluridine/Tipiracil 35mg/m2

Each cycle is 28 days. Two doses per day during days 1-5 with a two day rest for days 6 and 7. Then two doses per day for days 8-12, followed by a rest period for days 13-28 with the next cycle starting the day after day 28.

Group Type: EXPERIMENTAL

Trifluridine/Tipiracil

Intervention Type: DRUG

Oral medication

Interventions

Trifluridine/Tipiracil

Oral medication

Intervention Type: DRUG

Other Intervention Names

TAS-102

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years
• Life expectancy of ≥ 3 months
• Histologically or cytologically confirmed locally recurrent or metastatic breast cancer that is Estrogen receptor negative, Progesterone receptor negative, and HER2 normal on local testing
• Up to three prior chemotherapy regimens for advanced and/or metastatic disease
• Prior therapy with an anthracycline and a taxane in the adjuvant or metastatic setting or documented unsuitability
• Patients who developed advanced or metastatic disease within 6 months of completing adjuvant therapy are eligible with no prior therapy for advanced disease.
• Resolution of all chemotherapy- or radiation-related toxicities to ≤ grade 1 (except for stable sensory neuropathy ≤ grade 2 and alopecia) prior to commencement of study participation
• Eastern Cooperative Oncology Group performance status of 0 to 2
• Adequate renal function: creatinine clearance ≥ 40 mL/min Cockcroft and Gault formula
• Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, hemoglobin ≥ 10.0 g/dL (a hemoglobin <10.0 g/dL is acceptable if it is corrected by growth factor or transfusion), and platelet count ≥ 100 x 10^9/L
• Adequate liver function: bilirubin ≤ 1.5 times the upper limits of normal (ULN), alanine aminotransferase (ALT ≤ 3 x ULN (in the case of liver metastases ≤ 5 x ULN)
• Measurable disease (RECIST 1.1)
• Patients with known central nervous system (CNS) disease are eligible provided all of the following criteria are met:

• Measurable disease outside the CNS
• Metastases are limited solely to cerebellar and supratentorial lesions (i.e., no metastases to midbrain, pons, medulla, or spinal cord)
• If corticosteroids are required, the patient must be on a stable dose or tapering dose of corticosteroids for 4 weeks prior to enrolment as therapy for CNS disease
• Anticonvulsants at a stable dose are allowed as long as the patient has been seizure free for 3 weeks prior to enrolment
• No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization
• No evidence of progression or haemorrhage after completion of CNS directed therapy
• Note: Patients with new asymptomatic CNS metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible, if all other criteria above are met.
• Women of child-bearing potential and males with female partners with child bearing potential must use highly effective contraceptive measures while taking Trifluridine/tipiracil and for 6 months after stopping treatment. Trifluridine/tipiracil may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should add a barrier contraceptive method.
• Ability to understand and the willingness to sign a written informed consent document.
• Ability to take and retain oral medications

Exclusion Criteria

• Radiation therapy encompassing more than 30% of marrow
• Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for at least 2 weeks prior to randomization.
• Leptomeningeal disease
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Trifluridine/tipiracil .
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because Trifluridine/tipiracil is an agent with the potential for teratogenic or abortifacient effects.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tom Baker Cancer Centre

OTHER

Sponsor Role: collaborator

AHS Cancer Control Alberta

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patricia Tang, MD

Role: PRINCIPAL_INVESTIGATOR

Tom Baker Cancer Centre

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Countries

Canada

Other Identifiers

OZM-103

Identifier Type: -

Identifier Source: org_study_id