Combination Chemotherapy + Metformin + Dietary Supplement for Pancreatic Cancer

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

21 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot phase I trial studies the side effects of gemcitabine hydrochloride, nab-paclitaxel, metformin hydrochloride, and a standardized dietary supplement in treating patients with pancreatic cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Metformin hydrochloride, used for diabetes, may also help kill cancer cells. Dietary supplements (curcumin, vitamin D, vitamin K2, vitamin K1, B-6, high selenium broccoli sprouts, epigallocatechin gallate, L-carnitine, garlic extract, genistein, zinc amino chelate, mixed toxopherols, ascorbic acid, D-limonene) can block different targets in the cancer cell simultaneously and may slow down cancer growth. Giving gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, and metformin hydrochloride with a dietary supplement may work better in treating patients with pancreatic cancer that cannot be removed by surgery.

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.

What data supports the effectiveness of this drug combination for pancreatic cancer?

Research shows that gemcitabine, when combined with other drugs like cisplatin, can improve tumor response and time to progression in pancreatic cancer. Additionally, metformin may help overcome resistance to gemcitabine, making the treatment more effective. ^{1 2 3 4 5}

Is the combination of chemotherapy, metformin, and dietary supplements safe for pancreatic cancer patients?

Gemcitabine, a key component of the treatment, is generally well tolerated and can be safely administered with manageable side effects. It has been used in various combinations for pancreatic cancer, showing an acceptable safety profile. ^{6 7 8 9 10}

How is the drug combination of chemotherapy, metformin, and dietary supplement unique for pancreatic cancer?

This treatment is unique because it combines standard chemotherapy drugs like gemcitabine and paclitaxel with metformin, a diabetes medication, and a dietary supplement, which is not a common approach for pancreatic cancer. This combination aims to enhance the effectiveness of chemotherapy by potentially improving cancer cell response and reducing side effects. ^{1 2 11 12 13}

Research Team

Vincent Chung

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

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]

References

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

Does gemcitabine-based combination therapy improve the prognosis of unresectable pancreatic cancer? [2022]

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

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

3. 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]

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

Phase II study of gemcitabine and cisplatin in the treatment of patients with advanced pancreatic carcinoma. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

Resistance to gemcitabine in the pancreatic cancer cell line KLM1-R reversed by metformin action. [2022]

6. China pubmed.ncbi.nlm.nih.gov

Gemcitabine or gemcitabine plus cisplatin for in 42 patients with locally advanced or metastatic pancreatic cancer. [2022]

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

New agents in gastrointestinal malignancies: Part 2: Gemcitabine in clinical practice. [2022]

8. United States 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

A meta-analysis of gemcitabine containing chemotherapy for locally advanced and metastatic pancreatic adenocarcinoma. [2023]

10. 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]

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

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

12. England pubmed.ncbi.nlm.nih.gov

Gemcitabine combined with docetaxel for the treatment of unresectable pancreatic carcinoma. [2022]

13. Belgium pubmed.ncbi.nlm.nih.gov

[Gemcitabine: a new chemotherapy agent for solid cancers]. [2022]