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

NCT04149444 | Withdrawn Phase 2 DMC

• 1 other identifier: OZM-103
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  The Primary Endpoint ORR is calculated by taking the number of patients who at 8 weeks following initiation of Trifluridine/tipiracil have either a CR or a PR on first scan and dividing it over the total number of evaluable patients. Patients with stable disease are not included in this calculation.

  8 weeks

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 45 months.

• Disease Control Rate (DCR)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 45 months.

• Overall Survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 45 months.

• Safety and Tolerability: All adverse events experienced by all patients

  From date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 45 months.

• Quality of Life - Using EQ5D - A standardized questionnaire measuring quality of life

  From date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 32 months.

Study Arms (1)

ARM 1

EXPERIMENTAL

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.

Drug: Trifluridine/Tipiracil

Interventions

Trifluridine/Tipiracil DRUG

Oral medication

Also known as: TAS-102

ARM 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• AHS Cancer Control Alberta: lead
• Tom Baker Cancer Centre: collaborator

Study Sites (1)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Patricia Tang, MD

  Tom Baker Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: November 4, 2019
• Study Start: February 1, 2020
• Primary Completion: June 9, 2020
• Study Completion: June 9, 2020
• Last Updated: June 11, 2020

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)