Clinical Trials /

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

NCT04512261

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: TOPAZ: Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Women With HER2-Positive Breast Cancer Brain Metastases
  • Official Title: TOPAZ: Single Arm, Open Label Phase 1b/2 Study of Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Women With HER2-Positive Breast Cancer Brain Metastases

Clinical Trial IDs

  • ORG STUDY ID: IIT2019-21-Basho-TOPAZ
  • NCT ID: NCT04512261

Conditions

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

Interventions

DrugSynonymsArms
TucatinibTukysaTucatinib + Pembrolizumab + Trastuzumab
PembrolizumabKeytrudaTucatinib + Pembrolizumab + Trastuzumab
TrastuzumabHerceptinTucatinib + Pembrolizumab + Trastuzumab

Purpose

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 HER2+ BCBM not requiring urgent central nervous system (CNS) surgery will be enrolled in this study at Cedars-Sinai Medical Center and MD Anderson Cancer Center to determine the safe recommended dose of tucatinib in this combination. The efficacy of this combination in controlling CNS disease in patients with HER2+ BCBM will be assessed.

Trial Arms

NameTypeDescriptionInterventions
Tucatinib + Pembrolizumab + TrastuzumabExperimentalPatients 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.
  • Tucatinib
  • Pembrolizumab
  • Trastuzumab

Eligibility Criteria

        Inclusion Criteria:

          1. Women age ≥18 years.

          2. ECOG performance status of 0-2.

          3. HER2+ metastatic breast cancer as defined byASCO/CAP clinical practice guideline.

          4. New untreated CNS disease or CNS disease progression.

          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.

        Complete inclusion/exclusion criteria are detailed in the protocol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:24-week CNS disease control rate (DCR)
Time Frame:24 weeks
Safety Issue:
Description:Percentage of patients who experience objective tumor response [ partial response (PR) or complete response (CR) ] or stable disease as assessed by investigator per RANO-BM reads on protocol-specified MRIs of the brain.

Secondary Outcome Measures

Measure:CNS objective response rate (ORR)
Time Frame:From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.
Safety Issue:
Description:Proportion of participants with confirmed CR or PR per RANO-BM Criteria
Measure:Systemic ORR
Time Frame:From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.
Safety Issue:
Description:Proportion of participants with confirmed CR or PR per RECIST v.1.1
Measure:Progression-free survival (PFS)
Time Frame:From baseline to first documentation of true progression or symptomatic deterioration, or death due to any cause. Assessed up to 2 years.
Safety Issue:
Description:From date of registration to date of first documentation of true progression or symptomatic deterioration (as defined above), or death due to any cause. Patients last known to be alive and progression free are censored at date of last assessment. PFS will be assessed in the CNS and systemically.
Measure:Overall Survival (OS)
Time Frame:From baseline until death or 3 years, whichever occurs first.
Safety Issue:
Description:From date of registration to date of death due to any cause. Patient's last known to be alive are censored at date of last contact.
Measure:Toxicity profile of tucatinib, pembrolizumab, and trastuzumab co-administration
Time Frame:From first dose of study treatment until 30 days after the last dose of study treatment.
Safety Issue:
Description:Number of adverse events as assessed per CTCAE v.5.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Reva Basho

Trial Keywords

  • tucatinib
  • pembrolizumab
  • trastuzumab

Last Updated

August 12, 2020