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

NCT ID: NCT01834235

Last Updated: 2025-05-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2019-12-31

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.

Conditions

Pancreatic Cancer, Adult

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

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

nab-paclitaxel

Intervention Type: 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

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.

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

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

nab-paclitaxel

Intervention Type: 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

NPC-1C

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

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

nab-paclitaxel

Intervention Type: 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

NPC-1C

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

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

nab-paclitaxel

Intervention Type: 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

NPC-1C

Intervention Type: 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.

Interventions

Gemcitabine

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

Intervention Type: 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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

gemcitabine (Gemzar); Abraxane; Ensituximab

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Precision Biologics, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philip M Arlen, MD

Role: STUDY_DIRECTOR

Precision Biologics, Inc

Locations

California Pacific Medical Center

San Francisco, California, United States

Smilow Cancer Hospital- Yale

New Haven, Connecticut, United States

University of Miami

Miami, Florida, United States

National Cancer Institute

Bethesda, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beht Isreal Deaconess Medical Center

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Washington University in St. Louis

St Louis, Missouri, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Duke University

Durham, North Carolina, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36602796 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PB1201

Identifier Type: -

Identifier Source: org_study_id