Combination Chemotherapy for Pancreatic Cancer

Recruiting at 10 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Megestrol acetate

Disqualifiers: Brain metastases, Cardiac disease, Infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days for induction, then ongoing for chronic treatment

110 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using megestrol acetate, you must stop at least 10 days before starting the trial.

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

Research shows that combining nab-paclitaxel (a type of chemotherapy drug) with gemcitabine significantly improves survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. This combination has been shown to increase cancer cell death and may help overcome resistance to gemcitabine. ^{1 2 3 4 5}

Is the combination of nab-paclitaxel and gemcitabine safe for humans?

The combination of nab-paclitaxel and gemcitabine has been studied for safety in various clinical trials, including those for pancreatic cancer and non-small-cell lung cancer. These studies generally found the treatment to be tolerable, although the safety in more fragile patients remains less clear. ^{2 3 5 6 7}

What makes the combination chemotherapy with Gemcitabine, Nab-paclitaxel, and PEGPH20 unique for treating pancreatic cancer?

This treatment is unique because it combines Gemcitabine and Nab-paclitaxel, which have shown improved survival rates in pancreatic cancer, with PEGPH20, a drug that targets the tumor's surrounding tissue to enhance drug delivery. This combination aims to improve the effectiveness of chemotherapy by breaking down barriers that typically protect the cancer cells. ^{1 2 5 8 9}

What is the purpose of this trial?

The purpose of this study is to test any good and bad effects of the study drug called PEGPH20. PEGPH20 alone is considered investigational. The Food and Drug Administration (FDA) has not approved the marketing or sale of PEGPH20, but have authorized its use in research studies with humans. PEGPH20 could shrink the cancer but it also can cause side effects. PEGPH20 is an enzyme that breaks down a specific tissue component called hyaluronan produced by some tumors. Pancreatic tumors often have a large amount of hyaluronan. The removal of hyaluronan from tumors may decrease tumor growth.

Research Team

Kenneth H Yu, M.D.

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with advanced pancreatic adenocarcinoma who haven't had certain treatments. They must be in good physical condition, not pregnant or breastfeeding, and willing to use effective contraception. People with serious heart disease, recent strokes, other cancers within 3 years (except some skin cancers and cervical carcinoma), or those at high risk of bleeding can't join.

Inclusion Criteria

I am able to care for myself and perform normal activities.

Platelet count ≥100,000 plt/mm3

My pancreatic cancer is at an advanced stage and cannot be surgically removed.

Exclusion Criteria

Intolerance of dexamethasone

I have had a stroke or a mini-stroke in the past.

I do not have any health conditions that could interfere with the study treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gemcitabine, nab-paclitaxel, PEGPH20, and rivaroxaban based on thromboembolic event history

21 days for induction, then ongoing for chronic treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on thromboembolic events

1 year

Treatment Details

Interventions

• Gemcitabine
• Nab-paclitaxel
• PEGPH20

Trial Overview The study tests PEGPH20's effects on pancreatic cancer by breaking down hyaluronan in tumors. It's given alongside Gemcitabine and Nab-paclitaxel—common chemotherapy drugs—to see if it helps shrink the cancer more effectively than standard treatment alone.

Participant Groups

Group I: Patients without a prior thromboembolic event (TE) Experimental Treatment 3 Interventions

Patients without a prior TE will be treated with prophylactic dose and schedule of rivaroxaban (10 mg QD), together with standard dose and schedule of gemcitabine, nab-paclitaxel and PEGPH20.

Group II: Patients with a prior thromboembolic event (TE) Experimental Treatment 3 Interventions

Patients with a prior TE will be treated with therapeutic dose and schedule of rivaroxaban (15 mg BID for 21 days for induction if indicated, then 20 mg QD for chronic treatment), together with standard dose and schedule of gemcitabine, nab-paclitaxel and PEGPH20.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Halozyme Therapeutics

Industry Sponsor

Trials

47

Recruited

3,400+

Miami Cancer Institute

Collaborator

Trials

6

Recruited

950+

Findings from Research

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 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]

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 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]

In a retrospective study of 29 patients with advanced pancreatic carcinoma and elevated bilirubin levels, treatment with nanoparticle albumin-bound paclitaxel and gemcitabine (nab-P/G) was found to be safe, showing no unexpected toxicities.

The median overall survival for patients treated with nab-P/G was 11.7 months, with no significant differences in survival based on bilirubin levels, indicating that nab-P/G is a feasible treatment option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer suffering from cholestatic hyperbilirubinaemia-A retrospective analysis. Pelzer, U., Wislocka, L., Jühling, A., 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

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

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

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

3. 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]

4. Greece pubmed.ncbi.nlm.nih.gov

Co-treatment with gemcitabine and nab-paclitaxel exerts additive effects on pancreatic cancer cell death. [2022]

5. 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]

6. New Zealand 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. [2022]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer suffering from cholestatic hyperbilirubinaemia-A retrospective analysis. [2022]

9. Japan pubmed.ncbi.nlm.nih.gov

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