The Study of Gemcitabine Plus Nab-Paclitaxel in Combination With Pegvorhyaluronidase Alfa (PVHA; PEGPH20) and Pembrolizumab as Front-line Treatment for Metastatic Pancreatic Adenocarcinoma.

NCT04045730 | Withdrawn Phase 2

• 1 other identifier: 2000024450
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Pancreas Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) rate

  PFS is calculated as the number of days from date of registration to date of disease progression or symptomatic deterioration, or death due to any cause. PFS will be assessed from date of registration through study closure, up to 24 months.

  2 years

Secondary Outcomes (3)

• Overall Survival Rate median

  2 years

• Overall Response Rate (ORR)

  2 years

• Number of patients with treatment related adverse events as assessed by CTCAE v5.0

  2 years

Other Outcomes (5)

• To evaluate pre-treatment and on-treatment PD-L1

  2 years

• Evaluate tumor Hyaluronan (HA) levels

  2 years

• Change in immune effector cells with treatment

  2 years

Study Arms (1)

Patients with metastatic pancreatic ductal adenocarcinoma

EXPERIMENTAL

Patients must have histologically or cytologically confirmed pancreatic ductal adenocarcinoma, and all patients must have at least 15 unstained slides of formalin fixed paraffin embedded (FFPE) tumor tissue available or a pre-treatment core needle biopsy will be required as outlined in section 7.1.2.7. All patients will receive treatment with gemcitabine, nab-paclitaxel, PVHA, and pembrolizumab in 4-week cycles.

Drug: Gemcitabine

Interventions

Gemcitabine DRUG

All patients will receive treatment with gemcitabine, nab-paclitaxel, PVHA, and pembrolizumab.

Also known as: nab-paclitaxel, PVHA, pembrolizumab

Patients with metastatic pancreatic ductal adenocarcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with an untreated metastatic histologically confirmed diagnosis of stage IV pancreatic ductal adenocarcinoma will be enrolled in this study.
• Male participants:
• A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants:
• A female participant is eligible to participate if she is not pregnant not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Appendix 3
• A WOCBP who agrees to follow the contraceptive guidance in during the treatment period and for at least 120 days after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. Patients or their legally authorized representative must be informed of the investigational nature of this study.
• Measurable disease on computed tomography (CT) scan and/or MRI per RECIST 1.1 criteria. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Willing to undergo a pre-treatment core or excisional biopsy of a tumor lesion not previously irradiated, except for patients with 15 FFPE unstained slides of tumor tissue where a pre-treatment biopsy is optional. If 15 FFPE unstained slides are unavailable a pre-treatment biopsy is only mandatory if it can be obtained via a non-significant risk procedure. Significant risk procedures include (but are not limited to) biopsies of the brain, lung / mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus, stomach, or bowel. Any biopsy via significant risk procedure is optional. For patients who pursue an optional biopsy when a non-significant risk biopsy is possible the optional biopsy will serve as the pre-treatment tissue sample. Biopsy requirements are further outlined in section 7.1.2.7.
• Willing to undergo an on-treatment core or excisional tumor biopsy at week 8 (for the first 20 evaluable patients). Biopsy risk requirements for on-treatment biopsies are the same as the pre-treatment biopsy and outlined above and in section 7.1.2.7.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to day 1 of treatment. .
• Has a life expectancy of ≥ 20 weeks.
• Has adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study treatment.

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to the first dose of study treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received any prior systemic anti-cancer therapy including investigational agents for their metastatic pancreatic ductal adenocarcinoma prior to the first dose of study treatment. This includes any patients that have progressed ≤ 6 months of adjuvant therapy.
• Note: Participants must have recovered from all Adverse Events (AE) due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
• Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received any prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX40, CD137).
• Has received prior radiotherapy for metastatic pancreatic ductal adenocarcinoma prior to the first dose of study treatment.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has known history of Central Nervous System (CNS) metastases and/or carcinomatous meningitis, regardless of whether or not they have been treated.
• Has severe hypersensitivity (≥Grade 3) to gemcitabine, nab-paclitaxel, PVHA or pembrolizumab and/or any of their excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Yale University: lead

MeSH Terms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; pembrolizumab

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Michael Cecchin, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open-label single arm
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open-label single arm

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: August 5, 2019
• Study Start: November 15, 2019
• Primary Completion: December 31, 2019
• Study Completion: July 31, 2021
• Last Updated: January 9, 2020

Record last verified: 2020-01