Proglumide With Gemcitabine and Nab-Paclitaxel in PatientsWith Metastatic Pancreatic Ductal Adenocarcinoma (ProglumidePanc)

Phase I Study of Proglumide With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic DuctalAdenocarcinoma

This is a Phase I open labelled study to treat patients with metastatic pancreatic cancer with combination therapy using standard of care first line therapy with gemcitabine and nab-paclitaxel given days 1, 8, and 15 every 28 days, and proglumide. This is a phase 1 study with 3+3 design, enrolling3-12 patients over 2 planned dose levels of proglumide(maximum 6 patients per dose level). Proglumide will be tested at the daily dose of 1200 mg orally (PO) given as 400mg three times daily (TID) (dose level 1) or 1600 mg orally(PO) given as 800 mg twice a day (BID) (dose level 2). All cycles are 28 days. Patients will be monitored for safety and toxicity by laboratory blood testing and physical examinations.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Pancreatic Cancer
• Intervention / Treatment: Drug: Gemcitabine; Drug: Nab paclitaxel; Drug: Proglumide Dose level 1; Drug: Proglumide Dose level 2

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Comprehensive Cancer Center, Georgetown University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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
2. Age > 18 years at time of study entry.

3. Adequate normal organ and marrow function as defined below:

   • Hemoglobin ≥ 9.0 g/dL
   • Absolute neutrophil count (ANC) > 1500 permm3
   • Platelet count ≥100,000 per mm3)
   • Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).
   • Aspartate aminotransferase (AST) and alanine transaminase (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 Cockcroft-Gault formula.

4. 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).

5. Patients must have measurable disease by RECIST v1.1 and disease amenable to serial biopsy.
6. Subjects may not have received prior therapy with Gemcitabine (GEM)/Nab-paclitaxel (NAB-P).
7. Patients must have metastatic pancreatic ductal adenocarcinoma with adenocarcinoma as the dominant histology (biopsy-proven, primary tumor biopsy is acceptable for eligibility)
8. No prior systemic treatment for metastatic disease(neoadjuvant/adjuvant therapy is allowable but could not contain GEM or NAB-P).
9. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Exclusion Criteria:

1. 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.
2. 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 6months.
3. Blood anticoagulation that cannot be safely stopped for biopsy.
4. Subjects with poorly controlled medical conditions including asthma, chronic obstructive pulmonary disease, diabetes, seizure disorders, hepatic or renal failure.
5. Pregnant or nursing women.
6. 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.
7. Any concurrent chemotherapy, Investigational Product (IP), biologic, or hormonal therapy for cancer treatment.
8. 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.
9. History of allogenic organ transplantation.
10. 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 Adverse Events (AEs) or compromise the ability of the patient to give written informed consent

11. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and Tuberculosis (TB) testing in line with local practice), hepatitis B (HBV) (known positive HBV surface antigen (HBsAg) result), hepatitis C (HCV), 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.
12. 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.
13. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of proglumide therapy.
14. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
15. Patient is unable to swallow pills or has a malabsorption syndrome that would not enable the patient to properly absorb proglumide.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1:Proglumide TID with Gemcitabine and Nab-Paclitaxel; Proglumide given three times a day with gemcitabine and nab-paclitaxel	Drug: Gemcitabine; 1000mg/m2 IV given days 1, 8, and 15every 28 days (1 cycle); Other Names: Gemzar; Drug: Nab paclitaxel; 125 mg/m2 given days 1, 8, and 15every 28 days (1 cycle); Drug: Proglumide Dose level 1; Daily dose of 1200 mg orally given as400 mg orally (PO), three times a day(TID) (dose level 1)
Experimental: Dose Level 2:Proglumide BID with Gemcitabine and Nab-Paclitaxel; Proglumide given two times a day with gemcitabine and nab-paclitaxel	Drug: Gemcitabine; 1000mg/m2 IV given days 1, 8, and 15every 28 days (1 cycle); Other Names: Gemzar; Drug: Nab paclitaxel; 125 mg/m2 given days 1, 8, and 15every 28 days (1 cycle); Drug: Proglumide Dose level 2; Daily dose of 1600 mg orally given as800 mg orally (PO) twice a day (BID)(dose level 2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proglumide Recommended Phase II dose and schedule (RP2D)	Determination of the recommended phase II dose and schedule (RP2D) of proglumide in combination with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	median overall survival will be estimated using Kaplan-Meier curves.	through 2 years after end of treatment
Progression-free survival	median progression free survival will be estimated using Kaplan-Meier curves.	2 years
Objective response rate by RECIST v. 1.1	Every 8 weeks (± 7 days) radiographic imaging (CT or MRI) will be done to assess tumor burden according to RECIST v. 1.1	2 years
Change in tumor marker (CA19-9)	Maximum percent decrease in CA19-9 will be analyzed.	2 years

Collaborators and Investigators

• Sponsor: Georgetown University
• Investigators: Principal Investigator: Benjamin WE, MD, Georgetown University

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: August 24, 2023
• First Submitted That Met QC Criteria: August 24, 2023
• First Posted (Actual): August 30, 2023

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Pancreatic Cancer; Proglumide
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gastrointestinal Agents; Antineoplastic Agents, Phytogenic; Anti-Ulcer Agents; Paclitaxel; Proglumide; Gemcitabine
• Other Study ID Numbers: STUDY00001899

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No