PTC596 in Patients With Advanced Solid Tumors
- Registration Number
- NCT02404480
- Lead Sponsor
- PTC Therapeutics
- Brief Summary
This is a Phase 1, open-label, first-in-human, safety and pharmacokinetic study of PTC596 in patients with advanced cancer.
- Detailed Description
This is a Phase 1, open-label, first-in-human, safety and pharmacokinetic (PK) study of PTC596 in patients with advanced cancer. A variation of the traditional 3+3 dose escalation design will be employed.
PTC596 will be administered orally on a twice a week (biw) schedule. Each 4-week period of drug administration will be considered one cycle. The objective of the study will be to determine the recommended Phase 2 dose (RP2D) and to determine preliminary proof of mechanism of action.
Collectively, data from the Good Laboratory Practice (GLP) and non-GLP studies indicate that 40 mg/kg biw is approximately the severely toxic dose in 10% of animals (STD 10). Therefore, the starting dose in this study will be calculated as one-tenth of the human equivalent dose (HED) of 40 mg/kg biw in rats, which is 0.65 mg/kg biw.
In this study, escalating dose levels will be evaluated to determine the RP2D. Three patients will be enrolled at the starting dose level (0.65 mg/kg biw); if 1 of the 3 patients experiences a dose-limiting toxicity (DLT), an additional 3 patients will be enrolled at the same dose level. Thus, 3 to 6 patients will receive the starting dose level of 0.65 mg/kg. Dose escalation will continue until the occurrence of DLT in ≥2/6 patients at a given dose level. Dose escalation will occur in approximately 100% increments until Grade ≥2, first-cycle toxicity is seen in at least 2 patients across all dose levels, after which dose escalation will occur in smaller (50% or 33%) increments.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 31
- Patients must have histologically or cytologically confirmed solid malignancy that is metastatic or unresectable, for which standard curative measures do not exist, that has progressed on at least one line of standard therapy or for which no standard therapies exists
- Discontinuation of all other therapies (including other investigational drugs, radiotherapy, or chemotherapy) for the treatment of cancer ≥4 weeks (≥6 weeks if nitrosoureas, ≥12 weeks if radiotherapy) before initiation of study treatment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy of at least 3 months
- A measured or estimated creatinine clearance (CrCl) ≥60 mL/min/1.73 m2
- Prior bone marrow/hematopoietic stem cell transplantation
- History of solid organ, bone marrow, or progenitor cell transplantation
- History of major surgical procedure within 28 days prior to start of study treatment
- Evidence of ongoing systemic bacterial, fungal, or viral infection. Known human immunodeficiency virus (HIV) infection or acquired-immunodeficiency syndrome (AIDS)-related illness
- Any of the following in the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV), cerebrovascular accident, transient ischemic attack, other arterial thromboembolic event, or pulmonary embolism
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 3 PTC596 PTC 596 administered twice daily-2.6mg/kg Cohort 4 PTC596 PTC 596 administered twice daily-Dose level 5.2mg/kg Cohort 5 PTC596 PTC 596 administered twice daily-Dose level 10mg/kg Cohort 2 PTC596 PTC 596 administered twice daily-Dose level 1.3mg/kg Cohort 6 PTC596 PTC 596 administered twice daily-Dose level 7mg/kg Cohort 7 (Bio Marker cohort) PTC596 PTC 596 administered twice daily-Dose level 5.2mg/kg Cohort 1 PTC596 PTC 596 administered twice daily- Dose level 0.65mg/kg
- Primary Outcome Measures
Name Time Method Dose-limiting toxicities 28 days Determine the RP2D based on occurrence of DLTs and/or biological efficacy as determined by biomarker changes.
- Secondary Outcome Measures
Name Time Method Terminal half-life (t1/2). 28 days. Evaluate the terminal half-life (t1/2) of PTC 596 in humans.
Adverse effects 28days Define and describe the adverse effects of PTC596 in humans when orally administered on a biw schedule.
Time to Maximum Plasma Concentration (T max) 28days Evaluate the Time to Maximum Plasma Concentration (T max) of PTC596 in humans.
Antitumor activity 28days Describe any preliminary evidence of antitumor activity of PTC596.
Maximum Plasma Concentration (C max) 28 days Evaluate the Maximum Plasma Concentration (C max) of PTC596 in humans
Plasma Concentration at 24 hours 28days Evaluate the Plasma Concentration at 24 hours of PTC596 in humans
Area under the plasma concentration-time curve (AUC) 28 days Evaluate the area under the plasma concentration-time curve (AUC) of PTC 596 in humans.
Trial Locations
- Locations (4)
Duke University
🇺🇸Durham, North Carolina, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States