QUILT-3.010: A Study of Gemcitabine and Nab-paclitaxel With or Without NPC-1C to Treat Patients With Pancreatic Cancer

A Multicenter Phase I/II Randomized Phase II Study of Gemcitabine and Nab-Paclitaxel With or Without NPC-1C in Patients With Metastatic or Locally Advanced Pancreatic Cancer Previously Treated With FOLFIRINOX

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

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer, Adult
• Intervention / Treatment: Drug: Gemcitabine; Drug: nab-paclitaxel; Drug: NPC-1C

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.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Hospital- Yale
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Beht Isreal Deaconess Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St. Louis
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Subjects with recurrent, locally advanced unresectable or metastatic adenocarcinoma of the pancreas who have progressed after primary therapy with FOLFIRINOX or FOLFIRINOX-like regimen or were intolerant of it.
• IHC greater than or equal to 20 percent of tumor on tissue sections must stain with NPC-1C.
• 18 years of age or older.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have an anticipated life expectancy of greater than 8 weeks.
• Have recovered from any acute toxicity related to prior therapy.
• If female, is post-menopausal, surgically sterilized or willing to use an effective method of contraception for the duration of the study and for 3 months after the end of treatment. If male, has agreed to use barrier method for contraception for the duration of the study and for 3 months after the end of treatment.
• Must be willing to sign a written informed consent.

• Laboratory tests must meet minimum safety requirements

  1. Hemoglobin greater than or equal to 8.5 g/dL (may be receiving supportive therapy)
  2. ANC greater than or equal to 1,500 K/uL
  3. Platelets greater than or equal to 100 K/uL
  4. Total bilirubin less than or equal to 2 mg/dL
  5. ALT/AST less than or equal to 3 times ULN or less than or equal to 5 times ULN in the setting of liver metastases.
  6. Creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than 40 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, as calculated by the Cockcroft Gault formula.
• Men and women of all races and ethnic groups are eligible for this trial.

Exclusion Criteria

• Have received a second line chemotherapy after progressing on or not tolerating treatment with FOLFIRINOX as a first line. Prior adjuvant/neoadjuvant gemcitabine or gemcitabine-based radiation will not be counted as first line therapy.
• Have known brain metastases.
• Have had any major surgery within four weeks of enrollment.
• Have greater than grade 2 ascites at time of enrollment.
• Have received Gemcitabine for palliative treatment or progressed while receiving it or is within 3 months of completion in the adjuvant setting.
• Have uncontrolled concomitant illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Have serious medical or psychiatric illness that could, in the Investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Must not have other invasive malignancies within the past 3 years (with the exception of non-melanoma skin cancers or non-invasive bladder cancer).
• Is pregnant or breast-feeding, since the effects of NPC-1C on the developing human fetus and nursing infants are unknown and potentially harmful, women of child-bearing potential must agree to use adequate contraception (hormonal or double barrier method of birth control or complete abstinence) prior to study entry, for the duration of study participation, and for three months after the last dose of investigational agent.
• Have had any chemotherapy or systemic corticosteroids within 2 weeks of study entry.
• Have acquired, hereditary or congenital immunodeficiencies including cellular immunodeficiencies, hypogammaglobulinemia and dysgammaglobulinemia.
• Have a prior history of a documented hemolytic event.
• Have a history of hypersensitivity to human or mouse antibody products.
• Have a known history of HIV are excluded due to the possibility that Gemcitabine or NPC-1C(NEO-102) may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to Gemcitabine or NPC-1C(NEO-102).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Abraxane, 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.	Drug: Gemcitabine; Gemcitabine IV at a dose of 1000mg/m2 on days 1, 8, and 15 of a 4 week cycle.; Other Names: gemcitabine (Gemzar); Drug: 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) on Days 1, 7 and 15 for a 28 day cycle; Other Names: Abraxane
Experimental: Abraxane, gemcitabine, 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.	Drug: Gemcitabine; Gemcitabine IV at a dose of 1000mg/m2 on days 1, 8, and 15 of a 4 week cycle.; Other Names: gemcitabine (Gemzar); Drug: 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) on Days 1, 7 and 15 for a 28 day cycle; Other Names: Abraxane; Drug: NPC-1C; NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 28 day cycle. This will be administered 30 minutes after completion of the gemcitabine infusion.; Other Names: Ensituximab
Experimental: Phase 1: Dose Finding Dose level 1; 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.	Drug: Gemcitabine; Gemcitabine IV at a dose of 1000mg/m2 on days 1, 8, and 15 of a 4 week cycle.; Other Names: gemcitabine (Gemzar); Drug: 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) on Days 1, 7 and 15 for a 28 day cycle; Other Names: Abraxane; Drug: NPC-1C; NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 28 day cycle. This will be administered 30 minutes after completion of the gemcitabine infusion.; Other Names: Ensituximab
Experimental: Phase 1: Dose Finding Dose level -1; 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.	Drug: Gemcitabine; Gemcitabine IV at a dose of 1000mg/m2 on days 1, 8, and 15 of a 4 week cycle.; Other Names: gemcitabine (Gemzar); Drug: 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) on Days 1, 7 and 15 for a 28 day cycle; Other Names: Abraxane; Drug: NPC-1C; NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 28 day cycle. This will be administered 30 minutes after completion of the gemcitabine infusion.; Other Names: Ensituximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	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.	28 days
Overall Survival	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.	From 1st dose of study therapy until death in participants in Phase 2.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	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).	Time from the 1st dose of study drug until progression in patients in Arm A

Collaborators and Investigators

• Sponsor: Precision Biologics, Inc
• Investigators: Study Director: Philip M Arlen, MD, Precision Biologics, Inc

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): March 13, 2017
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: April 12, 2013
• First Submitted That Met QC Criteria: April 12, 2013
• First Posted (Estimated): April 17, 2013

Study Record Updates

• Last Update Posted (Actual): May 7, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Pancreatic cancer; Pancreatic neoplasms; Pancreatic cancer, adult; Adenoma of the pancreas; Carcinoma of the pancreas
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Paclitaxel
• Other Study ID Numbers: PB1201