Combination Chemotherapy for Pancreatic Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of a new enzyme treatment, PEGPH20, which may shrink pancreatic cancer by breaking down hyaluronan, a tissue component tumors use to grow. Participants will receive PEGPH20 combined with standard chemotherapy drugs, gemcitabine (Gemzar) and nab-paclitaxel (Abraxane). The trial divides participants into two groups: those with and without a history of blood clots, as this affects the dosage of the blood thinner rivaroxaban. It suits individuals with locally advanced or stage IV pancreatic cancer that cannot be surgically removed and who haven't recently undergone certain treatments. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options.

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.

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

Research has shown that combining PEGPH20 with gemcitabine and nab-paclitaxel has been tested in people with pancreatic cancer. In earlier studies, most patients tolerated this combination well. However, PEGPH20, an enzyme targeting hyaluronan in tumors, can cause side effects such as muscle pain, swelling, and blood clots.

Gemcitabine and nab-paclitaxel are commonly used to treat pancreatic cancer and are usually well-tolerated. Although PEGPH20 is not yet FDA-approved for sale, it can be used in research studies, and its safety is still under evaluation. Prospective trial participants should discuss potential risks and benefits with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for pancreatic cancer because it incorporates PEGPH20, which targets and breaks down hyaluronan—a substance in tumors that can hinder drug delivery. By clearing this barrier, PEGPH20 may enhance the effectiveness of gemcitabine and nab-paclitaxel, potentially improving drug penetration into tumors. Additionally, the use of rivaroxaban for patients with prior thromboembolic events aims to safely manage blood clots, while still allowing them to receive aggressive cancer treatment. This multifaceted approach has the potential to improve outcomes where traditional chemotherapy alone may fall short.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that combining PEGPH20 with gemcitabine and nab-paclitaxel may help treat pancreatic cancer. In this trial, participants will receive a combination of these drugs. Studies have found that adding PEGPH20 can shrink tumors in some patients. PEGPH20 breaks down a substance called hyaluronan, often found in large amounts in pancreatic tumors, which might slow tumor growth. Previous results are promising and suggest better outcomes than using gemcitabine and nab-paclitaxel alone. However, PEGPH20 can also cause side effects, and its full effectiveness is still under study. ^{1 2 3 5 6}

Who Is on the Research Team?

Kenneth H Yu, M.D.

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7499614/

Randomized Phase III Trial of Pegvorhyaluronidase Alfa With ... To evaluate the efficacy and safety of pegvorhyaluronidase alfa (PEGPH20) plus nab-paclitaxel/gemcitabine (AG) in patients with hyaluronan-high metastatic ...

2. asco.org asco.org/abstracts-presentations/ABSTRACT160151

Interim results of a randomized phase II study of PEGPH20 ... Interim results of a randomized phase II study of PEGPH20 added to nab‑paclitaxel/gemcitabine in patients with stage IV previously untreated pancreatic cancer.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.35.15_suppl.4008

Randomized phase II study of PEGPH20 plus nab- ... Secondary endpoints were PFS by HA level and ORR. Results: 279 pts were randomized; 231 are evaluable for efficacy. Of 246 pts with HA data, 84 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9516936/

Meta-analysis of gemcitabine plus nab-paclitaxel ... Even if surgical treatment improves patient outcomes, the 5-year survival rate is still < 10%[4]. Currently, gemcitabine and albumin combined with paclitaxel or ...

5. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04045730

The Study of Gemcitabine Plus Nab-Paclitaxel in ... This is an open-label single arm phase 2 study for patients with metastatic pancreatic ductal adenocarcinoma who have not received any prior systemic therapies.

6. onclive.com onclive.com/view/pegph20-misses-os-endpoint-in-metastatic-pancreatic-cancer

PEGPH20 Misses OS Endpoint in Metastatic Pancreatic ... Results showed that the addition of PEGPH20 led to a median OS of 11.2 months compared with 11.5 months in those who received gemcitabine/nab- ...