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

NCT01834235 | Terminated Phase 1 Results

• 1 other identifier: PB1201
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 12

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

Conditions

Pancreatic Cancer, Adult

Keywords

Pancreatic neoplasms; Pancreatic cancer; Pancreatic cancer, adult; Adenoma of the pancreas; Carcinoma of the pancreas

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Progression Free Survival

  Time from the 1st dose of study drug until progression in patients in Arm A

Study Arms (4)

Abraxane, gemcitabine

ACTIVE COMPARATOR

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; Drug: nab-paclitaxel

Abraxane, gemcitabine, NPC-1C

EXPERIMENTAL

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; Drug: nab-paclitaxel; Drug: NPC-1C

Phase 1: Dose Finding Dose level 1

EXPERIMENTAL

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; Drug: nab-paclitaxel; Drug: NPC-1C

Phase 1: Dose Finding Dose level -1

EXPERIMENTAL

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; Drug: nab-paclitaxel; Drug: NPC-1C

Interventions

Gemcitabine DRUG

Gemcitabine IV at a dose of 1000mg/m2 on days 1, 8, and 15 of a 4 week cycle.

Also known as: gemcitabine (Gemzar)

Abraxane, gemcitabine; Abraxane, gemcitabine, NPC-1C; Phase 1: Dose Finding Dose level -1; Phase 1: Dose Finding Dose level 1

nab-paclitaxel DRUG

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

Also known as: Abraxane

Abraxane, gemcitabine; Abraxane, gemcitabine, NPC-1C; Phase 1: Dose Finding Dose level -1; Phase 1: Dose Finding Dose level 1

NPC-1C DRUG

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.

Also known as: Ensituximab

Abraxane, gemcitabine, NPC-1C; Phase 1: Dose Finding Dose level -1; Phase 1: Dose Finding Dose level 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• Hemoglobin greater than or equal to 8.5 g/dL (may be receiving supportive therapy)
• ANC greater than or equal to 1,500 K/uL
• Platelets greater than or equal to 100 K/uL
• Total bilirubin less than or equal to 2 mg/dL
• 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.
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Precision Biologics, Inc: lead

Study Sites (12)

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Smilow Cancer Hospital- Yale

New Haven, Connecticut, 06510, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beht Isreal Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (1)

• Huffman BM, Basu Mallick A, Horick NK, Wang-Gillam A, Hosein PJ, Morse MA, Beg MS, Murphy JE, Mavroukakis S, Zaki A, Schlechter BL, Sanoff H, Manz C, Wolpin BM, Arlen P, Lacy J, Cleary JM. Effect of a MUC5AC Antibody (NPC-1C) Administered With Second-Line Gemcitabine and Nab-Paclitaxel on the Survival of Patients With Advanced Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial. JAMA Netw Open. 2023 Jan 3;6(1):e2249720. doi: 10.1001/jamanetworkopen.2022.49720.

  PMID: 36602796 DERIVED

MeSH Terms

Conditions

Pancreatic cancer, adult; Pancreatic Neoplasms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; ensituximab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Philip Arlen President and CEO
• Organization: Precision Biologics Inc.

philip.arlen@precision-biologics.com

3015008646

Study Officials

• Philip M Arlen, MD

  Precision Biologics, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Initial Phase 1 dose de-escalation design to determine the safe dose of NEO-102 in combination with gemcitabine. Then a Phase 2 randomized design to evaluate the safety and efficacy of gemcitabine and abraxane with or without NEO-102.

Study Record Dates

• First Submitted: April 12, 2013
• First Posted: April 17, 2013
• Study Start: April 1, 2013
• Primary Completion: March 13, 2017
• Study Completion: December 1, 2019
• Last Updated: May 7, 2025
• Results First Posted: May 7, 2025

Record last verified: 2025-02

Locations

US (12)