Tucatinib, Palbociclib and Letrozole in Metastatic Hormone Receptor Positive and HER2-positive Breast Cancer
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ClinicalTrials.gov Identifier: NCT03054363 |
Recruitment Status :
Active, not recruiting
First Posted : February 15, 2017
Last Update Posted : March 23, 2022
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Tracking Information | |||||||
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First Submitted Date ICMJE | February 7, 2017 | ||||||
First Posted Date ICMJE | February 15, 2017 | ||||||
Last Update Posted Date | March 23, 2022 | ||||||
Actual Study Start Date ICMJE | November 27, 2017 | ||||||
Estimated Primary Completion Date | March 18, 2023 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
Identify the pharmacokinetic (PK) properties of tucatinib and palbociclib current RP2D. [ Time Frame: 6 months ] PK assessments of blood levels of tucatinib and palbociclib will be performed on Cycle 1 Day 15 and Cycle 2 Day 1 of therapy. Plasma samples will be collected to measure levels of tucatinib and its hydroxyl metabolite, as well as levels of palbociclib and its metabolites at steady state on Cycle 1 Day 15. Plasma samples will also be collected prior to administration of tucatinib and palbociclib on the first day of Cycles 2 to assess trough levels.
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Tucatinib, Palbociclib and Letrozole in Metastatic Hormone Receptor Positive and HER2-positive Breast Cancer | ||||||
Official Title ICMJE | Phase IB/II Open-label Single Arm Study to Evaluate Safety and Efficacy of Tucatinib in Combination With Palbociclib and Letrozole in Subjects With Hormone Receptor Positive and HER2-positive Metastatic Breast Cancer | ||||||
Brief Summary | This is a multicenter run-in phase Ib / roll-over phase II study of triple targeted drug combination (HER2-targeted small molecule inhibitor tucatinib, CDK4/6 inhibitor palbociclib and aromatase inhibitor letrozole) as a first or second line of therapy in patients with metastatic hormone receptor positive and HER2-positive breast cancer. | ||||||
Detailed Description | This is a multicenter, single arm, open-label, run-in phase Ib / roll-over phase II study of novel HER2-targeted tyrosine kinase inhibitor tucatinib in combination with CDK4/6 inhibitor palbociclib and aromatase inhibitor letrozole in subjects with HR+/HER2+ locally advanced unresectable or metastatic breast cancer. The study will enroll post-menopausal women and premenopausal women if on treatment with or willing to be treated with standard ovarian suppression. The phase Ib part of the study will determine safety and tolerability of the combination of tucatinib, palbociclib and letrozole to confirm that current RP2D of tucatinib and FDA approved dosing of palbociclib remains the same in the triplet combination. The dose of letrozole will be constant through the study period. Once the safety of the combination is established, we will move to the phase II part of the study in the expansion cohort of subjects at RP2D for the purpose of assessing efficacy while further refining assessment of safety of the combination treatment. | ||||||
Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Breast Cancer | ||||||
Intervention ICMJE | Drug: Tucatinib in Combination with Palbociclib and Letrozole
Starting dose of combination therapy : Tucatinib 300 mg PO BID Palbociclib 125 mg PO daily 21 day on, 7 days off Letrozole 2.5 mg PO daily Dose modifications, if necessary: If Palbociclib toxicity increased: Tucatinib 300 mg PO BID Palbociclib 100 mg PO daily 21 day on, 7 days off Letrozole 2.5 mg PO daily If Tucatinib toxicity increased: Tucatinib 250 mg PO BID Palbociclib 125 mg PO daily 21 day on, 7 days off Letrozole 2.5 mg PO daily If Palbociclib and Tucatinib toxicity increased: Tucatinib 250 mg PO BID Palbociclib 100 mg PO daily 21 day on, 7 days off Letrozole 2.5 mg PO daily Additional dose levels per protocol if PKs indicate a significant change to the metabolism of Tucatinib regardless of clinical toxicity. Other Names:
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Study Arms ICMJE | Experimental: Tucatinib in Combination with Palbociclib and Letrozole
During phase 1b part of this trial (N=20 patients), treatment will be administered in cycles of 28 days and consist of tucatinib 300 mg PO BID, palbociclib 125 mg PO daily for 21 days followed by 7 days off, and letrozole 2.5 mg PO daily. Dose modifications of tucatinib, palbociclib and letrozole will be allowed per protocol. There will be an interim safety analysis performed after enrollment of 10 patients. Safety analysis will take into account proportion of patients requiring dose modifications or interruption for therapy because of toxicity. If excessive toxicity or significant changes in PKs are found, further patients will be enrolled at a lower starting dose level. There will be a second interim safety analysis after enrollment of 20 patients in the study. Once the recommended phase II dose (RP2D) has been determined, testing of this drug combination will be expanded in the phase II part of this trial (N=20 patients) to determine the progression-free survival (PFS) rate.
Intervention: Drug: Tucatinib in Combination with Palbociclib and Letrozole
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Active, not recruiting | ||||||
Actual Enrollment ICMJE |
42 | ||||||
Original Estimated Enrollment ICMJE |
40 | ||||||
Estimated Study Completion Date ICMJE | March 31, 2024 | ||||||
Estimated Primary Completion Date | March 18, 2023 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion criteria:
Exclusion criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 100 Years (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03054363 | ||||||
Other Study ID Numbers ICMJE | 16-1661.cc | ||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | University of Colorado, Denver | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | University of Colorado, Denver | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | University of Colorado, Denver | ||||||
Verification Date | March 2022 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |