A Phase 1b Study to Assess the Safety, Feasibility, Pharmacokinetics, and Activity of PTC299 Monotherapy or Combination Therapy With Hormonal Agents in Patients With Metastatic Breast Cancer
Overview
- Phase
- Phase 1
- Intervention
- PTC299
- Conditions
- Metastatic Breast Cancer
- Sponsor
- PTC Therapeutics
- Enrollment
- 33
- Locations
- 3
- Primary Endpoint
- Maximum Tolerated Dose (MTD) within the tested dose range.
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
Formation of new blood vessels (angiogenesis) is important for tumor growth in metastatic breast cancer. It is known that tumors make a protein called vascular endothelial growth factor (VEGF) and there are higher levels of VEGF in the tumors and blood of many women with metastatic breast cancer. VEGF stimulates the formation of blood vessels that supply the tumor with nutrients and oxygen. PTC299 is an oral drug that has been shown to decrease production of VEGF in animal models of human cancer. In these animal models, oral PTC299 administration decreases VEGF levels in the tumor and in the bloodstream, decreases blood vessel numbers in the tumor, and significantly slows or halts tumor growth. Safety studies in research animals indicate good tolerability at doses and drug levels that are higher than those planned for the clinical studies. Results from Phase 1a studies in healthy volunteers indicate that PTC299 achieves levels of PTC299 in the bloodstream that are known to be active in animal models of human cancer. This Phase 1b study is designed to test the hypothesis that PTC299 will be tolerable and will show evidence of VEGF reduction and antitumor activity when administered orally in combination with anastrozole (Arimidex®), letrozole (Femara®), or exemestane (Aromasin®) to women with metastatic breast cancer.
Detailed Description
The study will be conducted in 2 stages. In Stage 1 of the study, successive groups of 3 to 6 patients will receive progressively higher PTC299 dose levels; in this stage, treatment will be given in repeated 6-week cycles consisting of 4 weeks of oral PTC299 twice per day followed by a 2-week, no-drug period. During Stage 2, study candidates must be women with natural or induced suppression of ovarian function to post-menopausal levels who are receiving or are candidates for hormonal therapy. These subjects will receive continuous administration of PTC299, 100 mg/dose BID, in repeated 6-week cycles in combination with continuous administration of one of 3 hormonal agents. All planned PTC299 dose levels in all stages are expected to achieve circulating blood levels of PTC299 known to be active in animal models of human cancer. Treatment for each patient can continue as long as the therapy appears to be safely offering tumor control to that patient. Up to 36 evaluable patients will be accrued across both stages.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
1
PTC299 with an aromatase inhibitor
Intervention: PTC299
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD) within the tested dose range.
Time Frame: 6 Weeks
Secondary Outcomes
- Pharmacokinetics(6 Weeks)
- Antitumor activity as assessed by computed tomography (CT) scans and tumor markers(6 Weeks)
- Circulating angiogenic markers(6 Weeks)
- Overall safety profile(6 Weeks)
- Study drug compliance(6 Weeks)
- Tumor perfusion as assessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)(6 Weeks)
- Tumor metabolism as assessed by fluorodeoxyglucose positron emission tomography (FDG-PET)(6 Weeks)