Gemcitabine, Cisplatin, and Nab-Paclitaxel for Pancreatic Cancer

Overseen By Mihir M. Shah, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Disqualifiers: Peripheral neuropathy, Uncontrolled diabetes, CNS disease, others

Stay on Your Current Meds You can continue your current medications while participating

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: 11

Duration: 16 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for pancreatic cancer that can be surgically removed or is nearly removable. The goal is to evaluate the effectiveness of a chemotherapy drug combination—gemcitabine, cisplatin, and nab-paclitaxel—administered before surgery. These drugs stop cancer cells from growing and dividing. Ideal candidates for this trial have resectable or borderline resectable pancreatic cancer, meaning the cancer can potentially be surgically removed. Participants will receive the treatment in cycles to determine if it can improve surgical outcomes. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your specific 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 the combination of gemcitabine, cisplatin, and nab-paclitaxel is generally well-tolerated by patients. Studies have found this treatment promising in terms of safety and effectiveness. For example, one study reported a 71% overall response rate, indicating that many patients responded positively to the treatment.

Another study identified the most common side effects as low blood counts, tiredness, and numbness in the hands and feet, which are usually manageable. While side effects can occur, serious issues are less common.

This drug combination is also being tested for other cancers, such as biliary cancer, with positive results. This suggests they can be safe for people, although individual experiences may vary. For those considering joining a clinical trial, these studies indicate that this treatment has been tested before with encouraging safety data. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of gemcitabine, cisplatin, and nab-paclitaxel for pancreatic cancer because it offers a novel approach compared to the standard treatments like FOLFIRINOX or gemcitabine with nab-paclitaxel. This treatment combines the power of three drugs that work together to attack cancer cells more effectively. Nab-paclitaxel helps deliver paclitaxel more efficiently to the tumor, while cisplatin and gemcitabine work by damaging the DNA of cancer cells and preventing them from multiplying. This approach could potentially improve outcomes by enhancing the effectiveness of chemotherapy and increasing the chances of surgical resection.

What evidence suggests that gemcitabine, cisplatin, and nab-paclitaxel might be an effective treatment for pancreatic cancer?

Research has shown that a combination of three drugs—gemcitabine, cisplatin, and nab-paclitaxel—may effectively treat pancreatic cancer. In one study, patients who received this combination lived for a median of 19.2 months. Another study found that 71% of patients experienced tumor shrinkage, indicating the treatment's effectiveness for most people. Additionally, the treatment prevented cancer from worsening in 88% of patients. Compared to using gemcitabine alone, adding nab-paclitaxel and cisplatin significantly improved results. In this trial, participants will receive this combination treatment, which could be a good option for those with pancreatic cancer that can be surgically removed or is close to being removable. ^{1 2 6 7 8}

Who Is on the Research Team?

Mihir M. Shah

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with pancreatic cancer that can potentially be removed by surgery. Participants should have a type of cancer that's either resectable or borderline resectable, meaning it might be possible to surgically remove the tumor.

Inclusion Criteria

Able to adhere to study visit schedule and other protocol requirements

Serum total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)

I am a man or a woman not pregnant or breastfeeding.

Exclusion Criteria

Current abuse of alcohol or illicit drugs

I have moderate to severe numbness, tingling, or pain in my hands or feet.

Pregnancy or lactation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nab-paclitaxel, cisplatin, and gemcitabine intravenously on days 1 and 15 of each 28-day cycle, for up to 4 cycles

16 weeks

8 visits (in-person)

Surgery

Patients with stable disease, partial or complete response undergo surgical resection per standard of care

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Every 3-4 months

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Gemcitabine
• Nab-paclitaxel

Trial Overview The study is testing a combination of chemotherapy drugs (gemcitabine, cisplatin, and nab-paclitaxel) given before surgery to see if they improve survival rates compared to the standard treatment which involves surgery first followed by chemotherapy.

How Is the Trial Designed?

Group I: Treatment (nab-paclitaxel, cisplatin, gemcitabine) Experimental Treatment 8 Interventions

Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 15 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease, partial or complete response undergo surgical resection per standard of care. Additionally, patients undergo biopsy on study and undergo blood sample collection and CT or MRI at pre-study and on study.

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

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]

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 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 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]

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]

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]

Nab-paclitaxel has recently been introduced as a first-line treatment for metastatic pancreatic ductal adenocarcinoma (PDAC), showing promising improvements in patient outcomes after years of stagnation in treatment options.

The review highlights the unique mechanism of action of nab-paclitaxel, particularly its interaction with albumin and SPARC, which may enhance its efficacy in targeting cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel for metastatic pancreatic cancer: clinical outcomes and potential mechanisms of action. Al-Batran, SE., Geissler, M., Seufferlein, T., et al.[2015]

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 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 trial involving 84 patients with advanced non-small-cell lung cancer, the efficacy of weekly nab-paclitaxel plus cisplatin was found to be similar to that of gemcitabine plus cisplatin, with median progression-free survival of 4.8 months for nab-TP and 5.2 months for GP.

Nab-paclitaxel showed improved overall survival in patients with EGFR mutations (26.7 months) and those with a performance status of 0 (23.5 months) compared to gemcitabine, indicating potential benefits in specific patient subgroups while maintaining comparable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer: A phase II open-label clinical study. Qin, S., Yu, H., Wu, X., et al.[2022]

Citations

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Phase II clinical trial of nab‐paclitaxel plus cisplatin plus ... We achieved an ORR of 71% with two CRs, 12‐month OS of 65%, and median survival of 16+ months. The current phase II study was performed to ...

2. 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, ...

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2730639

Gemcitabine, Cisplatin, and nab-Paclitaxel for the ... Administration of nab-paclitaxel plus gemcitabine-cisplatin resulted in median progression-free survival of 11.8 months and median overall survival of 19.2 ...

4. gioncologynow.com gioncologynow.com/post/triplet-pancreatic-cancer-regimen-demonstrates-encouraging-survival

Triplet Pancreatic Cancer Regimen Demonstrates “ ... The overall response rate was 71%, and the disease control rate was 88%. Historically, nab-paclitaxel plus gemcitabine alone extend OS to 8.5 months in this ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03535727

A Study of Gemcitabine, Nab-paclitaxel, Capecitabine ... The purpose of this study is to evaluate the clinical activity of gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan (GAX-CI) in patients with ...

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Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment ... In this phase 2 trial that included 60 patients, administration of nab-paclitaxel plus gemcitabine-cisplatin resulted in median progression-free survival of 11 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04605913

Study Details | NCT04605913 | Nab-Paclitaxel + Cisplatin ... GCN is predicted to be the front-line therapy for biliary and pancreatic cancer in the future given excellent results of current early clinical trials (ORR ≥ 67 ...