Combination Chemotherapy + Metformin + Dietary Supplement for Pancreatic Cancer

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: Metformin

Must not be taking: Warfarin

Disqualifiers: Severe infections, Major surgery recovery, others

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

Compensation: Varies

Number of Visits: 6

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for pancreatic cancer that cannot be removed by surgery. It combines chemotherapy drugs, a diabetes medication (metformin), and a mix of dietary supplements to determine if they work better together to slow or stop cancer growth. Patients with pancreatic cancer who have not received certain types of chemotherapy may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I need to stop my current medications to join the trial?

You may need to stop taking certain medications to join the trial. If you are taking additional dietary or herbal supplements, you must stop them unless they are part of the trial. Also, if you require warfarin, you are not eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies have shown that gemcitabine hydrochloride, a common chemotherapy drug, helps pancreatic cancer patients live longer. However, it can also cause side effects like low blood counts and nausea. Paclitaxel, another chemotherapy drug used in the trial, may also cause blood-related side effects, but these are usually manageable.

Some studies have shown that metformin hydrochloride, often used for diabetes, can reduce death rates from cancer. It is generally well-tolerated, with common side effects including stomach upset and diarrhea.

The dietary supplements in the trial, such as curcumin and vitamin D, may offer potential benefits in cancer treatment, though more research is needed to fully understand their effects. They are generally considered safe, but their exact impact on cancer patients is still under study.

Overall, the treatment combination aims to effectively target cancer cells. Patients should be aware of possible side effects and discuss these with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for pancreatic cancer because it combines standard chemotherapy with metformin and a dietary supplement, which is a novel approach. Metformin, commonly used for diabetes, may help enhance the effectiveness of chemotherapy by altering cancer metabolism. Additionally, the inclusion of a dietary supplement aims to provide extra support in fighting cancer cells. This combination has the potential to improve outcomes by attacking the cancer from multiple angles, offering hope for better efficacy compared to the standard chemotherapy alone.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that the drugs gemcitabine hydrochloride and nab-paclitaxel can help treat pancreatic cancer by stopping tumor cells from growing and dividing. In this trial, participants will receive these drugs together, as they have demonstrated better results when combined. Additionally, participants will receive metformin, a common diabetes medication that might also help kill cancer cells and has shown promise in early cancer studies. The trial also includes a dietary supplement, which may contain ingredients like curcumin and vitamin D, to help slow cancer growth by targeting cancer cells in different ways. While more research is needed, these treatments show potential in fighting pancreatic cancer that cannot be removed by surgery. ^{6 7 8 9 10}

Who Is on the Research Team?

Vincent Chung

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with pancreatic cancer that can't be surgically removed. They should have normal bilirubin and creatinine levels, not be severely ill from other causes, able to swallow pills without vomiting issues, and not pregnant or nursing. Prior chemotherapy is mostly excluded except under certain conditions.

Inclusion Criteria

Your bilirubin level is less than 1.4 mg/dl.

Patients currently being treated for severe infections or who are recovering from major surgery or other intercurrent illnesses are ineligible until recovery is deemed complete by the investigator

You need to have a CT or MRI scan done within 4 weeks before joining the study.

Exclusion Criteria

Patients allergic to eggs are not eligible

Patients taking additional dietary/herbal supplements (excluding Senekot) outside of this protocol and refusing to stop are not eligible

Patients requiring warfarin are not eligible

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in

Participants receive metformin hydrochloride orally twice daily starting day -6 and dietary supplement orally twice daily starting day -3

1 week

1 visit (in-person)

Treatment

Participants receive gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation intravenously on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity

Up to 24 months

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6 months

2 visits per year (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine Hydrochloride
• Laboratory Biomarker Analysis
• Metformin Hydrochloride
• Paclitaxel Albumin-Stabilized Nanoparticle Formulation
• Quality-of-Life Assessment
• Therapeutic Dietary Intervention

Trial Overview The trial tests the combination of chemotherapy drugs gemcitabine hydrochloride and nab-paclitaxel with diabetes drug metformin hydrochloride and a dietary supplement mix aimed at targeting various aspects of cancer cell growth in patients with inoperable pancreatic cancer.

How Is the Trial Designed?

Group I: Treatment (gemcitabine, Abraxane, metformin, DS) Experimental Treatment 6 Interventions

Patients receive gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15. Patients also receive metformin hydrochloride PO BID starting day -6 and dietary supplement PO BID starting day -3. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Gemzar for:

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

Approved in United States as Gemzar for:

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

Approved in Canada as Gemzar for:

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

Approved in Japan as Gemzar for:

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

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

Gemcitabine has been established as a new standard treatment for pancreatic cancer, showing improved clinical benefits, time to progression, and survival compared to older treatments like 5-fluorouracil.

Combining gemcitabine with cisplatin has shown better tumor response and time to progression than gemcitabine alone, although its impact on overall survival is still being evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of advanced pancreatic cancer: a comparative analysis of randomized trials. Heinemann, V.[2022]

Gemcitabine has changed the perception of pancreatic cancer treatment, showing good tolerability and low side effects, making it a viable option for combination therapies with drugs like cisplatin and 5-fluorouracil.

Combination regimens with gemcitabine and cisplatin have shown response rates between 11.4% and 58% and median survival times of 7.4 to 10 months, while gemcitabine with 5-FU has lower response rates and survival times, indicating the need for further optimization of treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine-based combination treatment of pancreatic cancer. Heinemann, V.[2022]

In a phase III clinical trial involving 42 patients with locally advanced or metastatic pancreatic cancer, both gemcitabine (GEM) alone and GEM combined with cisplatin (CDDP) showed moderate efficacy, with overall response rates of 31.3% for GEM and 27.8% for the combination therapy.

The study demonstrated that GEM or GEM plus CDDP improved the quality of life and prolonged survival times, with 6-month survival rates of 81.3% for GEM and 61.6% for GEM plus CDDP, while maintaining a manageable toxicity profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine or gemcitabine plus cisplatin for in 42 patients with locally advanced or metastatic pancreatic cancer. Wang, X., Ni, Q., Jin, M., et al.[2022]

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]

Gemcitabine is a promising chemotherapy drug for various cancers, including pancreatic, lung, ovarian, and breast cancers, and is favored for its low toxicity, primarily affecting blood cells, making it suitable for patients who cannot handle more aggressive treatments.

When combined with other anticancer drugs like cisplatin and anthracyclines, gemcitabine shows high response rates, and it also enhances the effectiveness of radiotherapy, particularly in locally advanced cancer cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Gemcitabine: a new chemotherapy agent for solid cancers]. Klastersky, J., Awada, A.[2022]

Gemcitabine hydrochloride is an effective chemotherapy agent for advanced pancreatic cancer, demonstrating good tolerability and the ability to be administered safely on an outpatient basis.

The side effects associated with gemcitabine are manageable with proper monitoring and can be reversed through dose adjustments, highlighting the importance of oncology nurses in patient education and symptom management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New agents in gastrointestinal malignancies: Part 2: Gemcitabine in clinical practice. Stucky-Marshall, L.[2022]

In a phase III trial involving 319 patients with advanced pancreatic cancer, the combination of gemcitabine and capecitabine (GemCap) did not significantly improve overall survival compared to gemcitabine alone, with median survival times of 8.4 months for GemCap and 7.2 months for Gem.

However, in patients with a good performance status (Karnofsky score of 90-100), GemCap showed a significant improvement in median overall survival (10.1 months vs. 7.4 months for Gem), suggesting it may be a beneficial alternative for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. Herrmann, R., Bodoky, G., Ruhstaller, T., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02336087

Study Details | NCT02336087 | Gemcitabine Hydrochloride ... This pilot phase I trial studies the side effects of gemcitabine hydrochloride, nab-paclitaxel, metformin hydrochloride, and a standardized dietary ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6920852/

Gemcitabine Combination Nano Therapies for Pancreatic ... This review discusses the available drugs being co-administered with GEM and the limitations associated during the process of co-administration.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2405803325001062

Repurposing glucose-lowering drugs for cancer therapy This comprehensive review addresses the therapeutic potential of the main antidiabetic classes of glucose-lowering drugs with emerging anticancer effects.

4. clin.larvol.com clin.larvol.com/trial-detail/NCT02336087

Gemcitabine Hydrochloride, Paclitaxel Albumin-Stabilized ... Outcome Measure, Measure Description, Time Frame ; Analysis of biological correlates (Peripheral blood will be evaluated), Peripheral blood will be evaluated.

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2013-02230

Gemcitabine Hydrochloride and Paclitaxel Albumin ... This randomized phase II trial studies how well gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation with or without ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9459213/

The efficacy and safety of gemcitabine-based combination ... Our study supported that GEM-based combination therapy was more beneficial to improve patient's survival than GEM alone, while there was no additional benefits ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9108354/

c-Myc-PD-L1 Axis Sustained Gemcitabine-Resistance in ... Pancreatic cancer ranks fourth among cancer-related deaths, with a 5-years overall survival rate being below 10%. Gemcitabine (dFdC) has been ...

8. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/1750131

Adjuvant Chemotherapy With Gemcitabine and Long-term ... 01), with 5-year overall survival of 20.7% (95% CI, 14.7%-26.6%) vs 10.4% (95% CI, 5.9%-15.0%), respectively, and 10-year overall survival of ...

9. cancernetwork.com cancernetwork.com/view/odac-recommends-full-approval-gemzar-pancreatic-cancer

ODAC Recommends Full Approval for Gemzar ... The6 month survival rates were 46% and 31% for gemcitabine and 5-FUrespectively, and the 1 year survival rates were 18% and 2% forgemcitabine and 5-FU ...

10. onclive.com onclive.com/view/gemcitabine_asco_trials

Treatment with Gemcitabine (Gemzar) for Six Months After ... In this study, treatment with gemcitabine for six months after complete resection of pancreatic cancer significantly increased DFS and OS, compared with ...