L-glutamine + Chemotherapy for Pancreatic Cancer

Recruiting at 1 trial location

Overseen By Abrahm Levi, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jun Gong, MD

Must not be taking: Strong CYP2C8, CYP3A4 inhibitors

Disqualifiers: Metastatic chemotherapy, CNS metastases, others

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

Compensation: Varies

Number of Visits: 1

Duration: 12 months

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will enroll a total of 16 patients with advanced pancreatic cancer at Cedars-Sinai Medical Center. All subjects will receive combination therapy of gemcitabine, nab-paclitaxel, and L-glutamine. The study investigates what the appropriate dosage of L-glutamine is so that there is the lowest risk of side effects, and whether the supplement will make standard chemotherapy of gemcitabine and nab-paclitaxel more effective in treating advanced pancreatic cancer.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on strong CYP2C8 or CYP3A4 inhibitors or inducers within 1 week before starting nab-paclitaxel.

What data supports the effectiveness of the drug combination of L-glutamine, Gemcitabine, and Nab-paclitaxel for pancreatic cancer?

Research shows that combining nab-paclitaxel (a form of paclitaxel) with gemcitabine significantly improves survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. This combination has become a standard treatment option for metastatic pancreatic cancer due to its positive results in clinical trials. ^{1 2 3 4 5}

Is the combination of L-glutamine and chemotherapy safe for humans?

The combination of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and gemcitabine has been studied for safety in patients with pancreatic cancer, including elderly patients, and is generally considered safe, though specific side effects and tolerability can vary. These drugs are FDA-approved for cancer treatment, indicating they have passed safety evaluations for use in humans. ^{1 2 3 4 6}

What makes the drug combination of L-glutamine, Gemcitabine, and Nab-paclitaxel unique for treating pancreatic cancer?

The combination of L-glutamine with Gemcitabine and Nab-paclitaxel is unique because it adds a nutritional supplement (L-glutamine) to a standard chemotherapy regimen, which may help improve treatment outcomes or reduce side effects, although this specific combination is not yet a standard treatment for pancreatic cancer. ^{2 3 4 7 8}

Research Team

Jun Gong, MD

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

Adults with advanced pancreatic cancer who haven't had chemotherapy for metastatic disease can join. They must have good organ function, not be pregnant or breastfeeding, agree to use birth control, and be able to follow the study plan. People with severe pre-existing neuropathy, other active cancers, or conditions that could affect the study's outcome cannot participate.

Inclusion Criteria

You have a disease that can be measured using a specific standard.

I can take care of myself but might not be able to do heavy physical work.

My pancreatic cancer is advanced or cannot be surgically removed and I am referred to CSMC/SOCCI for first chemotherapy.

Exclusion Criteria

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

I haven't taken strong CYP2C8 or CYP3A4 drugs in the last week.

I have another cancer that is getting worse or needs treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

L-glutamine Pre-treatment

1-week administration of L-glutamine to measure baseline and post-glutamine monotherapy plasma metabolite levels

1 week

1 visit (in-person)

Treatment

Combination therapy of gemcitabine, nab-paclitaxel, and L-glutamine administered over 28-day cycles

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Gemcitabine
• L-glutamine
• Nab-paclitaxel

Trial Overview The trial is testing a combination of gemcitabine and nab-paclitaxel with L-glutamine in patients at Cedars-Sinai Medical Center. It aims to find the safest dose of L-glutamine and see if it boosts the effectiveness of standard chemotherapy in treating advanced pancreatic cancer.

Participant Groups

Group I: Gemcitabine + Nab-paclitaxel + L-glutamine Experimental Treatment 3 Interventions

For the dose-finding portion of this study, all subjects will receive a combination of L-glutamine, gemcitabine, and nab-paclitaxel which will be preceded by a 1-week (+/- 1 day) administration of L-glutamine. This 1-week administration of L-glutamine will facilitate measurement of baseline and post-glutamine monotherapy plasma metabolite levels prior to addition of gemcitabine and nab-paclitaxel. The combination therapy will be administered over 28-day cycles during the treatment period until disease progression, treatment intolerance, or withdrawal from the study. Patients are expected to be on treatment for 12 cycles.

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?

Jun Gong, MD

Lead Sponsor

Trials

1

Recruited

20+

Emmaus Medical, Inc.

Industry Sponsor

Trials

8

Recruited

380+

Findings from Research

In a study involving 221 patients with metastatic pancreatic ductal adenocarcinoma and poor performance status, the combination of NAB-paclitaxel and gemcitabine was found to be well tolerated, with manageable side effects such as anemia and neutropenia.

Both dosing regimens of NAB-paclitaxel (100 mg/m2 and 125 mg/m2) showed similar efficacy, with comparable response rates and median progression-free survival, indicating that this treatment is effective for fragile patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2. Macarulla, T., Pazo-Cid, R., Guillén-Ponce, C., et al.[2022]

Nab-paclitaxel plus gemcitabine (nab-P/Gem) is an effective first-line treatment for metastatic pancreatic cancer, with median overall survival rates ranging from 8.7 to 13.5 months across various studies involving a diverse patient population.

The combination of nab-P/Gem with additional agents is being actively researched, showing promise for improving outcomes in advanced pancreatic cancer, with median overall survival extending up to 17 months in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of pancreatic cancer. Kim, G.[2023]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

In a small study of 6 women with heavily pretreated HER2-negative metastatic breast cancer, the combination of nab-paclitaxel (nab-P) and bevacizumab (B), with or without gemcitabine (G), showed promising safety and preliminary efficacy, with only one patient experiencing significant toxicity.

Out of the 6 patients, 2 achieved partial responses and 4 had stable disease, indicating that this combination therapy may be effective, warranting further investigation in a formal phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. Lobo, C., Lopes, G., Silva, O., et al.[2022]

Gemcitabine-loaded human serum albumin nanoparticles (Gem-HSA-NPs) were successfully developed and showed a favorable controlled release, with an encapsulation rate of approximately 83% and a particle size of about 150 nm.

In vivo studies demonstrated that Gem-HSA-NPs significantly inhibited tumor growth in pancreatic cancer while exhibiting lower toxicity compared to other treatment groups, indicating their potential as a safer and more effective delivery method for gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An in vitro and in vivo study of gemcitabine-loaded albumin nanoparticles in a pancreatic cancer cell line. Yu, X., Di, Y., Xie, C., et al.[2022]

In a study of 27 elderly Japanese patients (aged ≥ 75) with non-curatively resectable pancreatic cancer, the combination of nanoparticle albumin-bound paclitaxel (nab-PTX) and gemcitabine (GEM) showed a high disease control rate of 92.6%, indicating strong efficacy in managing the disease.

Despite its effectiveness, the treatment was associated with significant adverse effects, including a 51.9% incidence of grade 3 or higher hemotoxicity and a 22% rate of grade ≥ 3 peripheral nerve disorders, highlighting the need for careful monitoring and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. Hasegawa, R., Okuwaki, K., Kida, M., et al.[2022]

In a study of 11 patients with metastatic or recurrent pancreatic cancer, the combination of nab-paclitaxel and gemcitabine showed promising efficacy, with a 6-month overall survival rate of 66.7% and a disease control rate of 90.9%.

The treatment was well tolerated, with no treatment-related deaths and manageable side effects, making nab-paclitaxel plus gemcitabine a potential standard treatment for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience]. Takeda, Y., Katsura, Y., Ohmura, Y., et al.[2022]

In a phase 3 trial involving 861 patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine significantly improved overall survival (8.5 months) compared to gemcitabine alone (6.7 months), with a hazard ratio for death of 0.72, indicating a 28% reduction in the risk of death.

The combination therapy also resulted in better progression-free survival (5.5 months vs. 3.7 months) and a higher overall response rate (23% vs. 7%), although it was associated with increased rates of adverse events like neutropenia and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. Von Hoff, DD., Ervin, T., Arena, FP., et al.[2022]

References

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

Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2. [2022]

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

nab-Paclitaxel for the treatment of pancreatic cancer. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. [2022]

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

An in vitro and in vivo study of gemcitabine-loaded albumin nanoparticles in a pancreatic cancer cell line. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience]. [2022]

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

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. [2022]