TOPAZ: Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Patients With HER2-Positive Breast Cancer Brain Metastases

NCT ID: NCT04512261

Last Updated: 2022-07-01

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-01
• Study Completion Date: 2024-06-01

Brief Summary

This is a single arm, open label trial to assess the safety and efficacy of tucatinib in combination with pembrolizumab and trastuzumab for the treatment of HER2+ breast cancer brain metastases (BCBM). A total of 33 patients with untreated or previously treated and progressing HER2+ BCBM not requiring urgent central nervous system (CNS)-directed therapy will be enrolled. The study will determine the recommended dose of tucatinib in this combination and assess the efficacy of this combination in controlling CNS disease in patients with HER2+ BCBM.

Conditions

Breast Cancer; Brain Metastases; HER2-positive Breast Cancer; CNS Disease

Study Design

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

Study Groups

Tucatinib + Pembrolizumab + Trastuzumab

Patients will receive a combination therapy of tucatinib with pembrolizumab and trastuzumab during the treatment period until progression, treatment intolerance, or patient withdrawal from study. Tucatinib and pembrolizumab are administered as experimental use while trastuzumab is administered per standard use. Patients are expected to be on treatment for at least 12 weeks.

Group Type: EXPERIMENTAL

Tucatinib

Intervention Type: DRUG

Initial dosage of trial treatment for tucatinib will be given as 300 mg (dispensed as 2 x 150 mg tablets) orally twice a day for Days 1 - 21 of each 3-week cycle during the treatment period.

Pembrolizumab

Intervention Type: DRUG

Initial dosage of trial treatment for pembrolizumab will be given as 200 mg by intravenous infusion every 3 weeks on Day 1 of each 3-week cycle during the treatment period. Pembrolizumab will be administered for a maximum of 35 doses.

Trastuzumab

Intervention Type: DRUG

Initial dosage of trial treatment for trastuzumab will be given as 8 mg/kg by intravenous (IV) infusion once on Day 1 of Cycle 1, and 6 mg/kg by IV every 3 weeks on Day 1 of each 3-week cycle starting on Cycle 2 during the treatment period.

Interventions

Tucatinib

Initial dosage of trial treatment for tucatinib will be given as 300 mg (dispensed as 2 x 150 mg tablets) orally twice a day for Days 1 - 21 of each 3-week cycle during the treatment period.

Intervention Type: DRUG

Pembrolizumab

Initial dosage of trial treatment for pembrolizumab will be given as 200 mg by intravenous infusion every 3 weeks on Day 1 of each 3-week cycle during the treatment period. Pembrolizumab will be administered for a maximum of 35 doses.

Intervention Type: DRUG

Trastuzumab

Initial dosage of trial treatment for trastuzumab will be given as 8 mg/kg by intravenous (IV) infusion once on Day 1 of Cycle 1, and 6 mg/kg by IV every 3 weeks on Day 1 of each 3-week cycle starting on Cycle 2 during the treatment period.

Intervention Type: DRUG

Other Intervention Names

Tukysa; Keytruda; Herceptin

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years.

2. ECOG performance status of 0-2.

3. HER2+ (as defined by ASCO/CAP clinical practice guideline) metastatic breast cancer.

4. Untreated or previously treated and progressing CNS disease.

5. Measurable CNS metastases.

6. Must be able to undergo MRI of the brain.

7. Adequate organ function.

Exclusion Criteria

1. Any indication for immediate CNS-directed therapy.

2. History of generalized or complex partial seizures.

3. Any other manifestation of neurologic progression that in the opinion of the treating physician is due to brain metastases.

4. Leptomeningeal disease.

5. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.

6. Prior therapy with tucatinib.

7. Active autoimmune disease that has required systemic treatment in excess of prednisone 10mg daily or equivalent in the past 2 years.

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

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Seagen Inc.

INDUSTRY

Sponsor Role: collaborator

Reva Basho

OTHER

Sponsor Role: lead

Responsible Party

Reva Basho

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Reva Basho, MD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

Countries

United States

Other Identifiers

IIT2019-21-Basho-TOPAZ

Identifier Type: -

Identifier Source: org_study_id