Proglumide + Chemotherapy for Pancreatic Cancer

(ProGem Trial)

Overseen By Ella Rutanen, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Georgetown University

Must not be taking: Anticoagulants, Chemotherapy, Biologics, others

Disqualifiers: Concurrent malignancy, Cardiovascular diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment while participating in this trial.

What data supports the effectiveness of the drug combination Proglumide + Chemotherapy for Pancreatic Cancer?

Research shows that the combination of nab-paclitaxel (Abraxane) and gemcitabine improves survival rates in patients with advanced pancreatic cancer compared to gemcitabine alone. This suggests that adding nab-paclitaxel to chemotherapy regimens can be beneficial for treating pancreatic cancer. ^{1 2 3 4 5}

Is the combination of Proglumide, Gemcitabine, and Nab-paclitaxel safe for humans?

The combination of Gemcitabine (Gemzar) and Nab-paclitaxel (Abraxane) has been studied for pancreatic cancer and shown to have manageable side effects, similar to those reported in clinical trials. While Proglumide's safety in this specific combination isn't detailed, it has been used in other contexts, suggesting it is generally safe for humans. ^{1 5 6 7 8}

What makes the drug Proglumide + Chemotherapy unique for pancreatic cancer?

The combination of Proglumide with chemotherapy drugs Gemcitabine and Nab-paclitaxel is unique because it explores a novel approach by adding Proglumide, which is not a standard component in existing pancreatic cancer treatments, potentially offering a new mechanism of action or enhanced effectiveness. ^{1 9 10 11 12}

Research Team

Benjamin Weinberg, MD

Principal Investigator

Georgetown University

Eligibility Criteria

Adults over 18 with metastatic pancreatic ductal adenocarcinoma who haven't had prior GEM/NAB-P treatment can join. They need good organ function, no recent other cancers except certain skin or localized prostate cancer, and must not have uncontrolled health issues like heart disease. Participants should be able to take oral medication and agree to use contraception.

Inclusion Criteria

Written informed consent and any locally-required authorization obtained from the patient prior to performing any protocol-related procedures, including screening evaluations

I am older than 18 years.

Your blood counts, liver and kidney function are within normal levels.

Exclusion Criteria

I haven't had cancer in the last 3 years, except for certain skin cancers, cervical cancer, or localized prostate cancer that was treated.

I cannot safely stop my blood thinners for a biopsy.

I am not currently on any cancer treatments like chemotherapy or hormone therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in Study

Determine the safety and tolerability of the 1200 mg daily dose of proglumide with standard of care GEM-NAB-P

4 weeks

Weekly visits for safety monitoring

Phase 2 Treatment

Randomized treatment with GEM-NAB-P plus placebo or proglumide at the RP2D

24 weeks

Visits every 2 weeks for blood work, every 4 weeks for vital signs, and every 8 weeks for imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Gemcitabine
• Nab paclitaxel
• Proglumide

Trial Overview The trial is testing Proglumide (1200 mg daily) combined with standard chemotherapy (Gemcitabine and Nab-paclitaxel) against a placebo plus the same chemo regimen in patients with advanced pancreatic cancer. The initial phase checks for safety before moving on to a larger Phase 2 study.

Participant Groups

Group I: Proglumide TID with Gemcitabine and Nab-Paclitaxel Experimental Treatment 3 Interventions

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

Group II: Placebo TID with Gemcitabine and Nab-Paclitaxel Experimental Treatment 3 Interventions

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

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

Findings from Research

In a study of 80 Italian patients with metastatic pancreatic cancer, treatment with nab-paclitaxel in combination with gemcitabine resulted in a median overall survival of 8 months and a median progression-free survival of 5 months, indicating its efficacy.

Nab-paclitaxel was well-tolerated and led to significant pain relief, with reductions in the tumor marker CA 19-9 correlating positively with overall survival, suggesting it may be a useful predictor of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. De Luca, R., Blasi, L., Alù, M., et al.[2022]

A study of 5465 patients with advanced pancreatic cancer in Ontario showed that the introduction of new chemotherapy regimens, GEMNAB and FOLFIRINOX, significantly improved overall survival rates over time, with median survival increasing from 5.6 months to 7.6 months between 2008 and 2018.

FOLFIRINOX was found to provide better overall survival compared to GEMNAB, particularly in younger and healthier patients, while GEMNAB still showed improved survival compared to the older standard treatment, gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. Raphael, MJ., Raskin, W., Habbous, S., et al.[2023]

In a study of 12 patients with elevated bilirubin levels, the combination of gemcitabine (GEM) and nab-paclitaxel (NabP) showed a median overall survival of 13.9 months, indicating improved efficacy compared to previous findings with GEM alone.

The treatment was found to be safe, with no admissions related to toxicity, and a disease control rate of 58%, suggesting that GEM-NabP can be effectively administered to patients who were previously excluded from studies due to hyperbilirubinemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-modified gemcitabine plus nab-paclitaxel front-line in advanced pancreatic ductal adenocarcinoma with baseline hyperbilirubinemia. Rogers, JE., Mizrahi, JD., Shroff, RT., et al.[2022]

In a study of patients with resected pancreatic ductal adenocarcinoma (PDAC), adjuvant chemotherapy with nab-paclitaxel plus gemcitabine (AG) significantly improved median disease-free survival (15.8 months) and overall survival (28.3 months) compared to gemcitabine alone (12.2 months and 20.6 months, respectively).

While AG showed better survival outcomes, it also led to a higher incidence of sensory neuropathy (53.3% in AG vs. 23.3% in GEM), indicating a trade-off between efficacy and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. Yin, ZZ., Zhao, ZM., Tang, WB., et al.[2020]

Recent treatment regimens for advanced pancreatic cancer, including gemcitabine, FOLFIRINOX, and nab-paclitaxel, have shown varying levels of efficacy, highlighting the importance of understanding their unique safety profiles.

Nurses play a crucial role in patient education and symptom management, as each treatment regimen has different adverse events that need to be identified and managed effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing Implications of Chemotherapy Agents and Their Associated Side Effects in Patients With Pancreatic Cancer. Hronek, JW., Reed, M.[2017]

In the NAPOLI 3 study involving 770 patients with metastatic pancreatic ductal adenocarcinoma, the NALIRIFOX treatment regimen resulted in a median overall survival of 11.1 months, which was significantly longer than the 9.2 months observed with the nab-paclitaxel and gemcitabine combination.

Both treatment groups experienced a high rate of grade 3 or higher adverse events (87% for NALIRIFOX and 86% for nab-paclitaxel-gemcitabine), indicating that while NALIRIFOX may improve survival, it does not significantly increase the risk of severe side effects compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Wainberg, ZA., Melisi, D., Macarulla, T., et al.[2023]

Itacitinib, a selective JAK1 inhibitor, combined with nab-paclitaxel and gemcitabine, showed an acceptable safety profile and clinical activity in patients with advanced solid tumors, including pancreatic cancer, with a 24% overall response rate across various doses.

The study indicated that while itacitinib was tolerated at lower doses, treatment-related toxicities such as neutropenia and fatigue were common, leading to dose adjustments; however, the study was terminated early due to negative results from a related phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. Beatty, GL., Shahda, S., Beck, T., et al.[2022]

A retrospective analysis of 59 patients with advanced refractory pancreatic cancer showed that the combination of nab-paclitaxel and gemcitabine (AG) is active as a second-line or beyond treatment, with 10% achieving a partial response and 47% having stable disease.

The median overall survival was 3.9 months and progression-free survival was 3 months, with toxicity levels similar to those reported in the earlier MPACT trial, indicating that AG has manageable side effects in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The nab-paclitaxel/gemcitabine regimen for patients with refractory advanced pancreatic adenocarcinoma. Palacio, S., Hosein, PJ., Reis, I., et al.[2020]

Fewer than 20% of pancreatic cancer patients have tumors confined to the pancreas, highlighting the need for effective treatment strategies for advanced disease, as about 40% present with locally advanced cancer.

Gemcitabine is established as the first-line treatment for pancreatic cancer, showing significant clinical benefits, and is being explored in combination with various other agents like 5-fluorouracil and irinotecan to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions in the treatment of pancreatic cancer. Haller, DG.[2022]

In a study of 486 patients with metastatic pancreatic cancer, those receiving nab-paclitaxel plus gemcitabine (nab-p + G) had a median age of 68 and worse performance status compared to those receiving FOLFIRINOX (FFX), who had a median age of 61 and better performance status.

Despite the differences in patient characteristics, the study found no significant differences in time to treatment failure (3.7 months for nab-p + G vs. 4.3 months for FFX) or overall survival (9.8 months for nab-p + G vs. 11.4 months for FFX), suggesting similar efficacy between the two chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes with First-Line Chemotherapy in a Large Retrospective Study of Patients with Metastatic Pancreatic Cancer Treated in a US Community Oncology Setting. Cartwright, TH., Parisi, M., Espirito, JL., et al.[2022]

In a study evaluating treatment options for metastatic pancreatic cancer, combination therapies like NAB-P + GEM, OX + GEM, CAP + GEM, and FOLFIRINOX were found to be more effective than gemcitabine (GEM) alone, providing better quality-adjusted life-years and life-years, despite being more expensive.

Among the evaluated regimens, NAB-P + GEM was identified as the most cost-effective option in the USA, with an incremental cost-utility ratio of US$204,833 per additional quality-adjusted life-year, making it a viable choice for treatment within a willingness-to-pay threshold of US$200,000.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic Evaluation for USA of Systemic Chemotherapies as First-Line Treatment of Metastatic Pancreatic Cancer. Gharaibeh, M., McBride, A., Alberts, DS., et al.[2022]

In a study of 58 patients with resectable metastatic pancreatic cancer treated with gemcitabine and docetaxel, the median overall survival was 52 months, with a 5-year survival rate of 49%, indicating a favorable outcome for this treatment approach.

The study found that while 52% of patients experienced significant toxicity (grade 3 or 4), the majority completed their treatment regimen, and the use of chemoradiation after gem/tax was positively associated with improved survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and Taxane Adjuvant Therapy with Chemoradiation in Resected Pancreatic Cancer: A Novel Strategy for Improved Survival? Kanji, ZS., Edwards, AM., Mandelson, MT., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. [2023]

3. China pubmed.ncbi.nlm.nih.gov

Dose-modified gemcitabine plus nab-paclitaxel front-line in advanced pancreatic ductal adenocarcinoma with baseline hyperbilirubinemia. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Nursing Implications of Chemotherapy Agents and Their Associated Side Effects in Patients With Pancreatic Cancer. [2017]

6. England pubmed.ncbi.nlm.nih.gov

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. [2023]

7. England pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. [2022]

8. China pubmed.ncbi.nlm.nih.gov

The nab-paclitaxel/gemcitabine regimen for patients with refractory advanced pancreatic adenocarcinoma. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Future directions in the treatment of pancreatic cancer. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Outcomes with First-Line Chemotherapy in a Large Retrospective Study of Patients with Metastatic Pancreatic Cancer Treated in a US Community Oncology Setting. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Economic Evaluation for USA of Systemic Chemotherapies as First-Line Treatment of Metastatic Pancreatic Cancer. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine and Taxane Adjuvant Therapy with Chemoradiation in Resected Pancreatic Cancer: A Novel Strategy for Improved Survival? [2022]