Clinical Trial of Alpelisb and Tucatinib in Patients With PIK3CA-Mutant HER2+ Metastatic Breast Cancer.
- Conditions
- HER2-positive Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT05230810
- Lead Sponsor
- Criterium, Inc.
- Brief Summary
Phase IB/II clinical trial of Alpelisb and Tucatinib in patients with PIK3CA-Mutant HER2-positive metastatic breast cancer.
- Detailed Description
This study is a multicenter, single arm, open-label, run-in phase Ib safety cohort with immediate roll over to a phase II clinical trial that will test the combination therapy of tucatinib with alpelisib in subjects with PIK3CA-mutant HER2+ locally advanced unresectable or metastatic breast cancer. Patients with PIK3CA-mutant HR-/HER2+ and HR+/HER2+ breast cancer may enroll, the latter cohort will receive concomitant treatment with standard doses of fulvestrant to block HR signaling. In phase Ib part, we will confirm the tolerability of tucatinib and alpelisib combination and determine the maximum tolerated dose (MTD). In phase II part, we will expand the testing of this drug combination at MTD to determine the PFS rate.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ib Safety Cohort /II Expansion Cohort Fulvestrant In phase Ib, the tolerability of tucatinib and alpelisib combination will be confirmed and maximum tolerated dose determined. Therapy will be administered in 28 day cycles of tucatinib 300 mg PO BID and alpelisib 250 mg PO daily (dose level 1). Treatment will continue until unacceptable toxicity, disease progression, withdrawal of consent, or study closure. Fulvestrant will also be administered in patients with HR+/HER2+ metastatic breast cancer. Once RP2D is determined, the study will be continued to phase II, and new patients will enroll at RP2D. All patients in phase IB part, who are remaining on study at the time of initiation of phase II, will be rolled over to phase II. At that time, their study drug doses will be modified as follows: (1) if a patient is on the drug doses lower than RP2D, doses will not be increased; (2) if a patient is on a higher doses compared to RP2D, doses of study drugs will be changed to RP2D. Ib Safety Cohort /II Expansion Cohort Alpelisib In phase Ib, the tolerability of tucatinib and alpelisib combination will be confirmed and maximum tolerated dose determined. Therapy will be administered in 28 day cycles of tucatinib 300 mg PO BID and alpelisib 250 mg PO daily (dose level 1). Treatment will continue until unacceptable toxicity, disease progression, withdrawal of consent, or study closure. Fulvestrant will also be administered in patients with HR+/HER2+ metastatic breast cancer. Once RP2D is determined, the study will be continued to phase II, and new patients will enroll at RP2D. All patients in phase IB part, who are remaining on study at the time of initiation of phase II, will be rolled over to phase II. At that time, their study drug doses will be modified as follows: (1) if a patient is on the drug doses lower than RP2D, doses will not be increased; (2) if a patient is on a higher doses compared to RP2D, doses of study drugs will be changed to RP2D. Ib Safety Cohort /II Expansion Cohort Tucatinib In phase Ib, the tolerability of tucatinib and alpelisib combination will be confirmed and maximum tolerated dose determined. Therapy will be administered in 28 day cycles of tucatinib 300 mg PO BID and alpelisib 250 mg PO daily (dose level 1). Treatment will continue until unacceptable toxicity, disease progression, withdrawal of consent, or study closure. Fulvestrant will also be administered in patients with HR+/HER2+ metastatic breast cancer. Once RP2D is determined, the study will be continued to phase II, and new patients will enroll at RP2D. All patients in phase IB part, who are remaining on study at the time of initiation of phase II, will be rolled over to phase II. At that time, their study drug doses will be modified as follows: (1) if a patient is on the drug doses lower than RP2D, doses will not be increased; (2) if a patient is on a higher doses compared to RP2D, doses of study drugs will be changed to RP2D.
- Primary Outcome Measures
Name Time Method Phase Ib Safety and Tolerability of alpelisib and tucatinib combination, summary of all AEs and SAEs on study as evaluated by NCI-CTCAE v 5.0 10 Months MTD of tucatinib and alpelisib in combination, summary of all AEs and SAEs on study as evaluated by NCI-CTCAE v 5.0
Phase II Efficacy of tucatinib combination evaluated by progression free survival (PFS) 20 Months PFS in the overall study population (the time from allocation to the first documented disease progression by RECIST1.1, or death due to any cause, whichever occurs first)
- Secondary Outcome Measures
Name Time Method Phase Ib Pharmacokinetic (PK) properties of alpelisib and tucatinib 10 Months Plasma concentrations of alpelisib and tucatinib measured at cycle 1 day 15 of therapy
Phase Ib Tumor response evaluation 10 Months CR, PR, or SD according to RECIST 1.1 (for subjects with CNS disease by RECIST 1.1 and RANO-BM); assessment of ORR (CR and PR), CBR (CR, PR and SD)
Phase Ib Duration of Response (DOR) 10 months Duration of response defined as the time from enrollment into clinical trial until objective tumor progression or death whichever occurs first.
Phase II Tumor response evaluation 20 months CR, PR, or SD according to RECIST 1.1 (for subjects with CNS disease by RECIST 1.1 and RANO-BM); assessment of ORR (CR and PR), CBR (CR, PR and SD)
Phase II Incidence, nature and severity of all AEs that occur on or after C1D1 of therapy 20 months Safety and tolerability of the combination therapy
Phase II Duration of Reponse (DOR) 20 months duration of response (DOR) defined as the time from enrollment into clinical trial until objective tumor progression or death whichever occurs first.
Trial Locations
- Locations (4)
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
University of Wisconsin Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
Louisiana State University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Cancer Care & Hematology-Fort Collins
🇺🇸Fort Collins, Colorado, United States