Zunsemetinib in Combination With Capecitabine in Patients With Hormone Receptor-Positive and HER2-Negative Metastatic Breast Cancer With Bone Metastasis
Phase 1
Not yet recruiting
- Conditions
- Interventions
- Registration Number
- NCT06374459
- Lead Sponsor
- Washington University School of Medicine
- Brief Summary
This is a phase Ib/II study evaluating the safety and efficacy of zunsemetinib (ATI-450) with capecitabine in patients with hormone receptor-positive and HER2-negative (HR+/HER2-) metastatic breast cancer (MBC).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 152
Inclusion Criteria
Not provided
Read More
Exclusion Criteria
Not provided
Read More
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase Ib: Zunsemetinib + Capecitabine Capecitabine Patients will receive zunsemetinib by mouth (PO) twice per day (BID) at an assigned dose along with capecitabine (1000 mg/m\^2 PO BID on Days 1-14 an every 21-day cycle). For patients enrolled in phase Ib, capecitabine is dosed on days 2-15 during cycles 1-2. Dose escalation of zunsemetinib will utilize a 3+3 design. A maximum of 3 dose levels of zunsemetinib will be tested, and the two highest dose levels which did not lead to more than 1 of 6 patients with DLT in cycle 1 will be chosen as the RP2D-L1 and RP2D-L2 for Phase II. If only one dose level of zunsemetinib was found tolerable, then only one RP2D will be chosen for Phase II. Phase II Arm 1: Standard of care anti-resorptive + Capecitabine Capecitabine Standard of care anti-resorptives will consist of bisphosphonate (zoledronic acid) is to be administered every 4-12 weeks, or denosumab is to be administered every 4-6 weeks, as per physician choice and institutional practice. In general, capecitabine will be taken twice daily at a dose of 1000 mg/m\^2 on Days 1 through 14 of every 21-day cycle. The first 4 patients enrolling to phase II will take capecitabine on a different schedule for PK purposes in Cycles 1 and 2 ONLY. Patients will take capecitabine at a dose of 1000mg/m\^2 on Days 2 through 15 of Cycles 1 and 2, and then on Days 1 through 14 starting with Cycle 3. Phase II Arm 1: Standard of care anti-resorptive + Capecitabine Denosumab Standard of care anti-resorptives will consist of bisphosphonate (zoledronic acid) is to be administered every 4-12 weeks, or denosumab is to be administered every 4-6 weeks, as per physician choice and institutional practice. In general, capecitabine will be taken twice daily at a dose of 1000 mg/m\^2 on Days 1 through 14 of every 21-day cycle. The first 4 patients enrolling to phase II will take capecitabine on a different schedule for PK purposes in Cycles 1 and 2 ONLY. Patients will take capecitabine at a dose of 1000mg/m\^2 on Days 2 through 15 of Cycles 1 and 2, and then on Days 1 through 14 starting with Cycle 3. Phase Ib: Zunsemetinib + Capecitabine Zumsemetinib Patients will receive zunsemetinib by mouth (PO) twice per day (BID) at an assigned dose along with capecitabine (1000 mg/m\^2 PO BID on Days 1-14 an every 21-day cycle). For patients enrolled in phase Ib, capecitabine is dosed on days 2-15 during cycles 1-2. Dose escalation of zunsemetinib will utilize a 3+3 design. A maximum of 3 dose levels of zunsemetinib will be tested, and the two highest dose levels which did not lead to more than 1 of 6 patients with DLT in cycle 1 will be chosen as the RP2D-L1 and RP2D-L2 for Phase II. If only one dose level of zunsemetinib was found tolerable, then only one RP2D will be chosen for Phase II. Phase II Arm 2: Zunsemetinib (RP2D-L1) + Capecitabine Zumsemetinib Patients will receive zunsemetinib by mouth (PO) twice per day (BID) at an assigned dose. In general, capecitabine will be taken twice daily at a dose of 1000 mg/m\^2 on Days 1 through 14 of every 21-day cycle. The first 4 patients enrolling to phase II will take capecitabine on a different schedule for PK purposes in Cycles 1 and 2 ONLY. Patients will take capecitabine at a dose of 1000mg/m\^2 on Days 2 through 15 of Cycles 1 and 2, and then on Days 1 through 14 starting with Cycle 3. Phase II Arm 3: Zunsemetinib (RP2D-L2) + Capecitabine Zumsemetinib Patients will receive zunsemetinib by mouth (PO) twice per day (BID) at an assigned dose. In general, capecitabine will be taken twice daily at a dose of 1000 mg/m\^2 on Days 1 through 14 of every 21-day cycle. The first 4 patients enrolling to phase II will take capecitabine on a different schedule for PK purposes in Cycles 1 and 2 ONLY. Patients will take capecitabine at a dose of 1000mg/m\^2 on Days 2 through 15 of Cycles 1 and 2, and then on Days 1 through 14 starting with Cycle 3. If only one dose level of zunsemetinib plus capecitabine was found tolerable in phase Ib testing, the phase II trial will proceed with 2:1 two-arm randomization with Arm 2 of capecitabine plus zunsemetinib and Arm 1 of capecitabine plus standard of care anti-resorptive agent. Phase II Arm 1: Standard of care anti-resorptive + Capecitabine Zoledronic acid Standard of care anti-resorptives will consist of bisphosphonate (zoledronic acid) is to be administered every 4-12 weeks, or denosumab is to be administered every 4-6 weeks, as per physician choice and institutional practice. In general, capecitabine will be taken twice daily at a dose of 1000 mg/m\^2 on Days 1 through 14 of every 21-day cycle. The first 4 patients enrolling to phase II will take capecitabine on a different schedule for PK purposes in Cycles 1 and 2 ONLY. Patients will take capecitabine at a dose of 1000mg/m\^2 on Days 2 through 15 of Cycles 1 and 2, and then on Days 1 through 14 starting with Cycle 3. Phase II Arm 2: Zunsemetinib (RP2D-L1) + Capecitabine Capecitabine Patients will receive zunsemetinib by mouth (PO) twice per day (BID) at an assigned dose. In general, capecitabine will be taken twice daily at a dose of 1000 mg/m\^2 on Days 1 through 14 of every 21-day cycle. The first 4 patients enrolling to phase II will take capecitabine on a different schedule for PK purposes in Cycles 1 and 2 ONLY. Patients will take capecitabine at a dose of 1000mg/m\^2 on Days 2 through 15 of Cycles 1 and 2, and then on Days 1 through 14 starting with Cycle 3. Phase II Arm 3: Zunsemetinib (RP2D-L2) + Capecitabine Capecitabine Patients will receive zunsemetinib by mouth (PO) twice per day (BID) at an assigned dose. In general, capecitabine will be taken twice daily at a dose of 1000 mg/m\^2 on Days 1 through 14 of every 21-day cycle. The first 4 patients enrolling to phase II will take capecitabine on a different schedule for PK purposes in Cycles 1 and 2 ONLY. Patients will take capecitabine at a dose of 1000mg/m\^2 on Days 2 through 15 of Cycles 1 and 2, and then on Days 1 through 14 starting with Cycle 3. If only one dose level of zunsemetinib plus capecitabine was found tolerable in phase Ib testing, the phase II trial will proceed with 2:1 two-arm randomization with Arm 2 of capecitabine plus zunsemetinib and Arm 1 of capecitabine plus standard of care anti-resorptive agent.
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) (Phase II only) From start of treatment through completion of follow-up (estimated to be 3 years and 10 months) Number of participants with adverse events (Phase Ib only) From start of treatment through 30 days after end of treatment (estimated to be 11 months) Number of participants with dose-limiting toxicities (Phase Ib only) Through end of 1st cycle (each cycle is 21 days) Recommended phase II dose of zunsemetinib (Phase Ib only) Through end of 1st cycle (each cycle is 21 days) Percent change in serum CTX (Phase II only) Baseline and Day 1 of week 7
- Secondary Outcome Measures
Name Time Method Clinical benefit rate (Phase II only) Through completion of treatment (estimated to be 10 months) Treatment-induced changes in pain as measured by Brief Pain Inventory (BPI) (Phase II only) Prior to start of 1st treatment, cycle 5 day 1, every 4 cycles thereafter (each cycle is 21 days), and at the time of progression (estimated to be 3 years and 10 months) Overall survival (OS) (Phase II only) From start of treatment through completion of follow-up (estimated to be 3 years and 10 months) Objective response rate (ORR) (Phase II only) Through completion of treatment (estimated to be 10 months) Treatment-induced changes in DEXA BMD (g/cm^2) at hip and spine (Phase II only) Baseline, end of cycle 8, and end of treatment (estimated to be 10 months) Number of participants with adverse events (Phase II only) From start of treatment through 30 days after end of treatment (estimated to be 11 months) Treatment-induced changes in DEXA BMD (g/cm^2) at hip and spine (Phase Ib only) Baseline, end of cycle 8 (each cycle is 21 days), and end of treatment (estimated to be 10 months) Treatment-induced changes in sCTX by clinical assay (Phase II only) Baseline, cycle 1 day 1 pre-dose, cycle 1 day 8 pre-dose, cycle 1 day 15 pre-dose, day 1 of subsequent cycles (each cycle is 21 days), and end of treatment (estimated to be 10 months) Treatment-induced changes in quality of life as measured by EORTC QLQ-C30 (Phase II only) Prior to start of 1st treatment, cycle 5 day 1, every 4 cycles thereafter (each cycle is 21 days), and at the time of progression (estimated to be 3 years and 10 months)
Trial Locations
- Locations (3)
The University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States