QUILT-3.010: A Study of Gemcitabine and Nab-paclitaxel With or Without NPC-1C to Treat Patients With Pancreatic Cancer
- Conditions
- Pancreatic Cancer, Adult
- Interventions
- Registration Number
- NCT01834235
- Lead Sponsor
- Precision Biologics, Inc
- Brief Summary
This was a Phase 1/2 multi-institution prospective open label study in which subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer who previously received treatment with chemotherapy with FOLFIRINOX or FOLFIRINOX-like regimen received the investigational agent NEO-102 (NPC-1C).
The Phase 1 portion of this study evaluated the safety of NEO-102 in combination with Gemcitabine in a dose de-escalation design with a starting dose of 1.5 mg/kg/dose. If 2 of 6 patients experience DLT, the dose will be de-escalated to 1 mg/kg/dose to evaluate the safety of NEO-102 in combination with Gemcitabine. .
In the Phase 2 portion patients were randomized into one of two arms:
A: NPC-1C with gemcitabine and nab-paclitaxel or B: gemcitabine and nab-paclitaxel
- Detailed Description
During Part 1 of the study, the safe and tolerable dose of NEO-102 in combination with Gemcitabine will be determined using a dose de-escalation design. The starting dose of NEO-102 is 1.5 mg/kg/dose (Dose level 1). If 2 of 6 patients experience a DLT at the starting dose, the dose of NEO-102 will be de-escalated to 1 mg/kg/dose, and up to 6 patients will be treated at this Dose Level -1. Upon completion of the phase I study up to 90 patients be randomized to one of two arms:
A: Patients will receive NPC-1C(NEO-102) infusion at the safe dose, and nab-paclitaxel (125 mg/m2 as a 30 minute infusion, maximum infusion time not to exceed 40 minutes) followed by gemcitabine (1000 mg/m2 as a 30 minute infusion) for 3 consecutive weeks (on Day 1, 7 and 15 ) followed by a week of rest (for a 28 day cycle).
OR B: Patients will receive on Day 1, 7 and 15 nab-paclitaxel (125 mg/m2 as a 30 minute infusion, maximum infusion time not to exceed 40 minutes) followed by gemcitabine (1000 mg/m2 as a 30 minute infusion) for 3 consecutive weeks (on Day 1, 7 and 15). NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV 30 minutes following the completion of the gemcitabine on days 1 and 15 of the 28 day cycle.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 81
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Abraxane, gemcitabine Gemcitabine Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 consecutive weeks followed by a week of rest. Abraxane, gemcitabine nab-paclitaxel Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 consecutive weeks followed by a week of rest. Abraxane, gemcitabine, NPC-1C Gemcitabine Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 consecutive weeks followed by a week of rest. Patients on arm B will receive NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 4-week cycle. This will be administered 30minutes after completion of the gemcitabine infusion. Phase 1: Dose Finding Dose level 1 nab-paclitaxel The initial portion of this protocol was a phase 1 (3+3) dose de-escalation design the initial dose of 1.5 mg/kg/dose: Gemcitabine was administered at the dose of 1000 mg/m2 by IV infusions over 30 minutes on days 1, 8, and 15 followed in 30 minutes by NPC-1C(NEO-102) infusion at 1.5 mg/kg IV on days 1 and 15 of a 4-week cycle. Three subjects were enrolled on this dose level and all 3 subjects completed without any dose limiting toxicity. This dose was established for the Phase 2 portion of the study. At this time FDA approved the combination of Gemcitabine and Abraxane in this patient population. Hence the Phase 2 portion added Abraxane to the regimen. Abraxane, gemcitabine, NPC-1C nab-paclitaxel Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 consecutive weeks followed by a week of rest. Patients on arm B will receive NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 4-week cycle. This will be administered 30minutes after completion of the gemcitabine infusion. Abraxane, gemcitabine, NPC-1C NPC-1C Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 consecutive weeks followed by a week of rest. Patients on arm B will receive NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 4-week cycle. This will be administered 30minutes after completion of the gemcitabine infusion. Phase 1: Dose Finding Dose level 1 Gemcitabine The initial portion of this protocol was a phase 1 (3+3) dose de-escalation design the initial dose of 1.5 mg/kg/dose: Gemcitabine was administered at the dose of 1000 mg/m2 by IV infusions over 30 minutes on days 1, 8, and 15 followed in 30 minutes by NPC-1C(NEO-102) infusion at 1.5 mg/kg IV on days 1 and 15 of a 4-week cycle. Three subjects were enrolled on this dose level and all 3 subjects completed without any dose limiting toxicity. This dose was established for the Phase 2 portion of the study. At this time FDA approved the combination of Gemcitabine and Abraxane in this patient population. Hence the Phase 2 portion added Abraxane to the regimen. Phase 1: Dose Finding Dose level 1 NPC-1C The initial portion of this protocol was a phase 1 (3+3) dose de-escalation design the initial dose of 1.5 mg/kg/dose: Gemcitabine was administered at the dose of 1000 mg/m2 by IV infusions over 30 minutes on days 1, 8, and 15 followed in 30 minutes by NPC-1C(NEO-102) infusion at 1.5 mg/kg IV on days 1 and 15 of a 4-week cycle. Three subjects were enrolled on this dose level and all 3 subjects completed without any dose limiting toxicity. This dose was established for the Phase 2 portion of the study. At this time FDA approved the combination of Gemcitabine and Abraxane in this patient population. Hence the Phase 2 portion added Abraxane to the regimen. Phase 1: Dose Finding Dose level -1 Gemcitabine The initial portion of this protocol was a phase 1 (3+3) dose de-escalation design the initial dose of 1.5 mg/kg/dose: Gemcitabine was administered at the dose of 1000 mg/m2 by IV infusions over 30 minutes on days 1, 8, and 15 followed in 30 minutes by NPC-1C(NEO-102) infusion at 1 mg/kg IV on days 1 and 15 of a 4-week cycle. No patients were enrolled on this arm because Dose Level 1 was determined to be safe. Phase 1: Dose Finding Dose level -1 nab-paclitaxel The initial portion of this protocol was a phase 1 (3+3) dose de-escalation design the initial dose of 1.5 mg/kg/dose: Gemcitabine was administered at the dose of 1000 mg/m2 by IV infusions over 30 minutes on days 1, 8, and 15 followed in 30 minutes by NPC-1C(NEO-102) infusion at 1 mg/kg IV on days 1 and 15 of a 4-week cycle. No patients were enrolled on this arm because Dose Level 1 was determined to be safe. Phase 1: Dose Finding Dose level -1 NPC-1C The initial portion of this protocol was a phase 1 (3+3) dose de-escalation design the initial dose of 1.5 mg/kg/dose: Gemcitabine was administered at the dose of 1000 mg/m2 by IV infusions over 30 minutes on days 1, 8, and 15 followed in 30 minutes by NPC-1C(NEO-102) infusion at 1 mg/kg IV on days 1 and 15 of a 4-week cycle. No patients were enrolled on this arm because Dose Level 1 was determined to be safe.
- Primary Outcome Measures
Name Time Method Safety and Tolerability 28 days To determine the safety and tolerability of NPC-1C monoclonal antibody therapy in combination with Gemcitabine in subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer who failed or did not tolerate first line chemotherapy of FOLFIRINOX and whose tumors bind NPC-1C.
Overall Survival From 1st dose of study therapy until death in participants in Phase 2. To determine whether (only in participants in the Phase 2 portion (Arm A and Arm B) NPC-1C (NEO-102) in combination with Gemcitabine and nab-Paclitaxel will increase the overall survival (OS) compared to Gemcitabine and nab-Paclitaxel alone in patients with metastatic, locally advanced unresectable or recurrent pancreatic cancer previously treated with FOLFIRINOX and whose tumors bind NPC-1C by at least 20% on IHC.
- Secondary Outcome Measures
Name Time Method Progression Free Survival Time from the 1st dose of study drug until progression in patients in Arm A To determine the progression free survival (PFS) and response rate (RR) of patients with metastatic or locally advanced unresectable or recurrent pancreatic cancer who progressed following or did not tolerate chemotherapy of FOLFIRINOX or FOLFIRINOX-like regimen when receiving the combination of NPC-1C(NEO-102) monoclonal antibody, Gemcitabine and nab-Paclitaxel (Arm A).
Trial Locations
- Locations (12)
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beht Isreal Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
University of Miami
🇺🇸Miami, Florida, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Smilow Cancer Hospital- Yale
🇺🇸New Haven, Connecticut, United States
Duke University
🇺🇸Durham, North Carolina, United States
National Cancer Institute
🇺🇸Bethesda, Maryland, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States