Gemcitabine + Nab-Paclitaxel for Pancreatic Cancer

Overseen By Danielle Trunzo

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Laith Abushahin

Disqualifiers: Brain metastases, Active infections, HIV, 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: 7

Duration: 28-day cycles

53 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new timing for administering two chemotherapy drugs, gemcitabine (Gemzar) and nab-paclitaxel (Abraxane), to determine if it helps treat metastatic pancreatic cancer. Chemotherapy stops cancer cells from growing and spreading. The trial seeks to discover if altering the timing of nab-paclitaxel administration enhances treatment effectiveness. Individuals diagnosed with metastatic pancreatic cancer who have not yet received chemotherapy may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that patients must not have received previous chemotherapy or investigational therapy for metastatic pancreatic cancer, except under certain conditions. It's best to discuss your current medications with the trial team to get a clear answer.

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

Research has shown that gemcitabine and nab-paclitaxel are generally well-tolerated treatments for pancreatic cancer. In one study with 69 patients who had advanced pancreatic cancer, this treatment combination proved safe for most people. Another study confirmed that gemcitabine plus nab-paclitaxel is a safe first treatment option for patients with this type of cancer.

While some side effects can occur, these studies suggest that most patients can undergo the treatment without serious issues. This evidence supports the safety of using gemcitabine and nab-paclitaxel together for treating pancreatic cancer. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for pancreatic cancer?

Researchers are excited about the combination of gemcitabine and nab-paclitaxel for treating pancreatic cancer because it offers a unique approach compared to the typical standard care. While traditional treatments often involve either gemcitabine or nab-paclitaxel alone, this combination uses both drugs together, potentially enhancing their effectiveness. The synergy between gemcitabine, which disrupts cancer cell DNA, and nab-paclitaxel, which interferes with cell division, may lead to more comprehensive cancer cell destruction. Additionally, the treatment is given in a specific schedule that might enhance patient outcomes while minimizing toxicity.

What evidence suggests that this treatment might be an effective treatment for pancreatic cancer?

Research has shown that combining gemcitabine and nab-paclitaxel can extend the lives of people with pancreatic cancer. In this trial, participants will receive this combination treatment. Specifically, studies found that patients receiving both drugs lived an average of 8.5 months, compared to 6.7 months for those who received only gemcitabine. This combination also delayed cancer progression. The drugs work by preventing cancer cells from growing and spreading. Altering the administration of nab-paclitaxel might enhance its effectiveness for pancreatic cancer patients. ^{1 6 7 8 9}

Who Is on the Research Team?

Laith Abushahin, MBBS

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with metastatic pancreatic adenocarcinoma confirmed by tissue analysis. Participants must have measurable tumors, not be pregnant or breastfeeding, and agree to use effective contraception. No prior chemotherapy for metastatic cancer is allowed, but past adjuvant therapy over 6 months ago is acceptable. They need a certain level of blood cells (neutrophils, platelets) and hemoglobin.

Inclusion Criteria

You are not pregnant or breastfeeding.

You must agree to use a very effective method of birth control during the study and for 3 months after the study ends. Effective birth control methods are listed below.

If you are a woman who could become pregnant, you must have a negative pregnancy test before starting the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gemcitabine IV over 30 minutes on days 1 and 15 and nab-paclitaxel IV over 30 minutes on days 3 and 17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28-day cycles

4 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months monthly, then every 3 months

Monthly visits for 3 months, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• Nab-paclitaxel

Trial Overview The study tests an optimized infusion schedule of two chemotherapy drugs: Gemcitabine and Nab-paclitaxel in patients with advanced pancreatic cancer. The goal is to see if changing the timing of Nab-paclitaxel improves treatment outcomes.

How Is the Trial Designed?

Group I: Treatment (gemcitabine, nab-paclitaxel) Experimental Treatment 2 Interventions

Patients receive gemcitabine IV over 30 minutes on days 1 and 15 and nab-paclitaxel IV over 30 minutes on days 3 and 17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

Laith Abushahin

Lead Sponsor

Trials

1

Recruited

50+

Anne Noonan

Lead Sponsor

Trials

2

Recruited

60+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 study of 28 patients with advanced non-small-cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, the combination of nanoparticle albumin-bound paclitaxel (nab-PTX) and gemcitabine (GEM) showed limited efficacy, with a median progression-free survival of only 3.1 months and an overall response rate of 17.9%.

The treatment was associated with significant safety concerns, particularly a 14.3% incidence of grade 3 interstitial pneumonia, which was deemed unacceptable, highlighting the need for careful consideration of this combination therapy in NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multi-center, Phase II trial of nab-paclitaxel and gemcitabine in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. Tachihara, M., Kiriu, T., Hata, A., 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]

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]

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]

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]

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]

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]

Nab-paclitaxel, when combined with gemcitabine, significantly improves overall survival in adults with metastatic pancreatic cancer, reducing the risk of death by 28% compared to gemcitabine alone, based on a multinational phase III study.

The treatment has a manageable safety profile, with most adverse events being grade 3 or lower, and common side effects like neutropenia and peripheral neuropathy are generally reversible with dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albumin-bound paclitaxel: a review of its use for the first-line combination treatment of metastatic pancreatic cancer. Hoy, SM.[2021]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1304369

Increased Survival in Pancreatic Cancer with nab ... The median overall survival was 8.5 months in the nab-paclitaxel–gemcitabine group as compared with 6.7 months in the gemcitabine group (hazard ratio for death, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6254624/

Efficacy of Nab-Paclitaxel Plus Gemcitabine and ... The primary outcome measures were OS and progression-free survival (PFS). OS was determined from the date of first chemotherapy to death from any cause, whereas ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5298402/

A modified regimen of biweekly gemcitabine and nab ... Treatment with nab-paclitaxel with gemcitabine demonstrates a survival advantage when compared with single-agent gemcitabine. However, the combination is ...

4. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-020-06758-9

Quality of life study of patients with unresectable locally ... Combination therapy with gemcitabine + nab-paclitaxel had better overall and progression-free survival than gemcitabine alone.

5. cancer.gov cancer.gov/types/pancreatic/research/nab-paclitaxel-gemcitabine

Nab-Paclitaxel Plus Gemcitabine for Metastatic Pancreatic ... Patients who received the drug combination had a median overall survival of 8.5 months, compared with 6.7 months for patients treated with gemcitabine alone.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02267707

Pharmacokinetic and Safety Study of Nab®-Paclitaxel (ABI ... The purpose of this study is to determine the safety and pharmacokinetic profile of nab®-paclitaxel (ABI-007) plus gemcitabine in subjects with advanced ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9869579/

The efficacy and safety of Nab-paclitaxel plus gemcitabine ... The outcomes of 69 patients with metastatic pancreatic cancer were identified retrospectively from March 2017 to February 2022. Of these, 5 ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1424390324000772

Treatment outcomes of gemcitabine plus nab-paclitaxel in ... Gemcitabine plus nab-paclitaxel (GnP) therapy has been shown to improve the prognosis in patients with metastatic pancreatic cancer (PC); however, the efficacy ...

9. tandfonline.com tandfonline.com/doi/full/10.1080/1120009X.2023.2190712

Clinical outcome and safety profile of metastatic pancreatic ... Our study corroborates the data on the efficacy and safety of gemcitabine plus nab-paclitaxel as a first-line regimen, in a large group of patients with ...