A Study of MK-8109 (Vintafolide) Given Alone or With Chemotherapy in Participants With Advanced Cancers (MK-8109-001)
- Conditions
- Advanced Cancer
- Interventions
- Registration Number
- NCT01688791
- Lead Sponsor
- Endocyte
- Brief Summary
This trial will be conducted in three parts. Part A is a dose escalation trial followed by a dose confirmation trial in folate receptor (FR) 100% endometrial cancer participants. The primary hypothesis of this trial is that administration of vintafolide in combination with carboplatin and paclitaxel is safe and tolerable. Part B is a single dose, dose escalation, pharmacokinetic (PK), and QTc interval trial. The primary objectives include determination of the maximum single tolerated dose of vintafolide and to evaluate the effect of this single maximum dose on the QTc interval. Part C is a weekly dose escalation trial of vintafolide followed by a dose confirmation. The primary hypothesis of this part is that weekly vintafolide has acceptable safety and tolerability in participants with advanced cancers.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 37
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: Vintafolide BIW Vintafolide Vintafolide, intravenously (IV), on Days 1, 4, 8, and 11 of each 21-day cycle. Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle. Paclitaxel, IV, at a dose of 175 mg/m\^2, administered on Day 1 of each 21-day cycle Part A: Vintafolide BIW Carboplatin Vintafolide, intravenously (IV), on Days 1, 4, 8, and 11 of each 21-day cycle. Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle. Paclitaxel, IV, at a dose of 175 mg/m\^2, administered on Day 1 of each 21-day cycle Part A: Vintafolide BIW Paclitaxel Vintafolide, intravenously (IV), on Days 1, 4, 8, and 11 of each 21-day cycle. Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle. Paclitaxel, IV, at a dose of 175 mg/m\^2, administered on Day 1 of each 21-day cycle Part A: Vintafolide TIW Paclitaxel Vintafolide, intravenously (IV) on Days 1, 3, 5, 8, 10, and 12 of each 21-day cycle. Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle. Paclitaxel, IV, at a dose of 175 mg/m\^2, administered on Day 1 of each 21-day cycle Part A: Vintafolide TIW Vintafolide Vintafolide, intravenously (IV) on Days 1, 3, 5, 8, 10, and 12 of each 21-day cycle. Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle. Paclitaxel, IV, at a dose of 175 mg/m\^2, administered on Day 1 of each 21-day cycle Part A: Vintafolide TIW Carboplatin Vintafolide, intravenously (IV) on Days 1, 3, 5, 8, 10, and 12 of each 21-day cycle. Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle. Paclitaxel, IV, at a dose of 175 mg/m\^2, administered on Day 1 of each 21-day cycle Parts B & C: Vintafolide Single Dose & Weekly (QW) Vintafolide Single dose, dose escalation, vintafolide (Part B) followed by 2 week observation. Those completing Part B will have the option to continue on to Part C (weekly dosing, dose finding, on Days 1, 8, and 15 in a 21-day cycle until disease progression or toxicity) unless they experience severe and/or persistent drug related toxicity.
- Primary Outcome Measures
Name Time Method Part B: Change from Baseline in QTc interval 30 minutes pre-dose and up to 2 hours post-dose Part C: Number of Participants Experiencing an Adverse Event (AE) Up to 18 weeks (six 3-week cycles) Parts A and C: Number of participants with dose-limiting toxicities (DLTs) Cycle 1 (21 days)
- Secondary Outcome Measures
Name Time Method Number of participants whose best response is partial response (PR) or complete response (CR) Week 6 Disease control rate Week 6 Part B: Pharmacokinetics (PK) of vintafolide, including Area Under the Curve (AUC) and Maximum Concentration (Cmax) Day 1 Part B: PK of Vintafolide Metabolites, including AUC and Cmax Day 1 Progression free survival Week 6