Proglumide and Chemotherapy for Metastatic Pancreatic Cancer

NCT05827055 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY0000697801899
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2 study with an open labelled lead-in study to approximately treat 30 patients \[6 subjects for Lead-in and 24 for Phase 2\] enrolled with metastatic pancreatic cancer with combination therapy using standard of care first line therapy with GEM-NAB-P (GEM 1000mg/m2 IV and NAB-P 125 mg/m2 given days 1, 8, and 15 every 28 days, and proglumide will be tested at the daily dose of 1200 mg orally given as 400 mg po TID. The lead-in study will determine the safety and tolerability of the 1200 mg daily dose of proglumide with standard of care GEM-NAB-P. If 0 or 1 of a total of 6 patients at 400mg experiences a DLT, then we will proceed to the Phase 2 randomized trial.

Conditions

Metastatic Pancreatic Cancer

Keywords

Proglumide; Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Safety of oral proglumide therapy at 1200mg daily dose with chemotherapy

  The number of abnormal serum chemistry values occurring in those on proglumide compared to those on placebo

  18 months

Secondary Outcomes (4)

• Fibrosis in the pancreatic tumor microenvironment

  3 years

• Overall survival (OS)

  4 years

• Progression-free survival

  4 years

• Effects of proglumide on Pain

  4 years

Study Arms (2)

Proglumide TID with Gemcitabine and Nab-Paclitaxel

EXPERIMENTAL

Proglumide given three times a day with gemcitabine and nab-paclitaxel

Drug: Gemcitabine; Drug: Nab paclitaxel; Drug: Proglumide

Placebo TID with Gemcitabine and Nab-Paclitaxel

EXPERIMENTAL

Placebo given three times a day with gemcitabine and nab-paclitaxel

Drug: Gemcitabine; Drug: Nab paclitaxel; Drug: Placebo

Interventions

Gemcitabine DRUG

1000mg/m2 IV given days 1, 8, and 15 every 28 days (1 cycle)

Also known as: Gemzar

Placebo TID with Gemcitabine and Nab-Paclitaxel; Proglumide TID with Gemcitabine and Nab-Paclitaxel

Nab paclitaxel DRUG

125 mg/m2 given days 1, 8, and 15 every 28 days (1 cycle)

Also known as: Abraxane

Placebo TID with Gemcitabine and Nab-Paclitaxel; Proglumide TID with Gemcitabine and Nab-Paclitaxel

Proglumide DRUG

Daily dose of 1200 mg orally given as 400 mg orally (PO), three times a day (TID) in vegan capsules

Also known as: Milid

Proglumide TID with Gemcitabine and Nab-Paclitaxel

Placebo DRUG

Placebo given in vegan. capsules orally three times a day

Also known as: Avicel capsules

Placebo TID with Gemcitabine and Nab-Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Written informed consent and any locally-required authorization (e.g., HIPAA in the USA) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
• Age \> 18 years at time of study entry.
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) \> 1500 per mm3
• Platelet count ≥100,000 per mm3)
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).
• AST and ALT ≤2.5 x ULN of normal unless liver metastases are present, in which case it must be ≤5x ULN
• Creatinine clearance (CL) \>60 mL/min using the Cockroft-Gault formula.
• Evidence of post-menopausal status or negative urine or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments, or if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
• Patients must have measurable disease by RECIST v1.1 and disease amenable to serial biopsy.
• Subjects may not have received prior therapy with GEM/NAB-P.
• Patients must have metastatic pancreatic ductal adenocarcinoma with adenocarcinoma as the dominant histology (biopsy-proven, primary tumor biopsy is acceptable for eligibility)
• No prior systemic treatment contain GEM or NAB-P.

You may not qualify if:

• Subjects with a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer, or localized prostate cancer following definitive therapy.
• Subjects with uncontrolled cardiovascular diseases (congestive heart failure, symptoms of coronary artery disease, cardiac arrhythmias) or who have suffered a myocardial infarction in the preceding 6 months.
• Blood anticoagulation that cannot be safely stopped for biopsy.
• Subjects with poorly controlled medical conditions including asthma, chronic obstructive pulmonary disease, diabetes, seizure disorders, hepatic or renal failure.
• Pregnant or nursing women.
• Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device \[IUD\], or abstinence) prior to study entry, for the duration of study participation, and for 6 months thereafter.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea or inability to digest and absorb pills, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies).
• Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible.
• Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Testing for tuberculosis, hepatitis B and C and HIV is not a requirement for screening for the clinical trial.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational drug. Note: Patients, if enrolled, should not receive live vaccine while receiving IP and up to 30 days after the last dose of IP.

Sponsors & Collaborators

• Georgetown University: lead

Study Sites (1)

Lombardi Comprehensive Cancer Center, Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Taxes; Albumin-Bound Paclitaxel; Proglumide; Cellulose

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; Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Glutamine; Amino Acids, Basic; Amino Acids; Amino Acids, Diamino; Glucans; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Benjamin Weinberg, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double blinded
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2023
• First Posted: April 24, 2023
• Study Start: January 31, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: May 23, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)