Second-line Study of PEGPH20 and Pembro for HA High Metastatic PDAC

NCT03634332 | Unknown Phase 2 FDA Drug

• 1 other identifier: PCRT 16-001
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 5

Brief Summary

This study is the study of the combination of PEGPH20 and Pembrolizumab (MK-3475) for patients with previously treated Hyaluronan High (HA-high) metastatic pancreatic ductal adenocarcinoma. This study is an interventional, unblinded, open label study. Approximately 35 subjects will be enrolled. The trial will require approximately a total of 18 months, including 12 months for enrollment, with an additional 6 months for patient follow-up, data collection and study closure. Each subject will participate in the trial from the time the subject signs the Informed Consent Form (ICF) through the final contact. After a screening phase of up to 21 days, eligible subjects will receive PEGPH20 beginning with Cycle 1 Day 1, on Days 1, 8 15 of every 3 week-cycles and pembrolizumab beginning on Cycle 1 Day 1 (2-4 hrs after PEGPH20), every 3-week-cycles. Treatment with PEGPH20 and pembrolizumab will continue until progressive disease (PD), unacceptable adverse events (AEs), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdraws consent, pregnancy of the subject, noncompliance with trial treatment or procedure requirements, subject receives 35 treatments (approximately 24 months) of pembrolizumab, or administrative reasons requiring cessation of treatment. Subjects who discontinue for reasons other than PD will have post-treatment follow-up for disease status until PD, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. All subjects will be followed by telephone for overall survival (OS) until death, withdrawal of consent, or the end of the study. After the end of treatment, each subject will be followed for 30 days for AE monitoring. Serious adverse events (SAE) and events of clinical interest (ECI) will be collected for 90 days after the end of treatment or for 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier.

Conditions

Pancreatic Ductal Adenocarcinoma; Pancreatic Cancer; Pancreatic Neoplasms

Keywords

pancreatic; pancreas; cancer; adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Evaluate the progression-free survival (PFS) for patients treated with pembrolizumab and PEGPH20

  PFS will be assessed from Date of registration through study closure, up to 24 months. 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.

Secondary Outcomes (5)

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

  Safety and Tolerability using CTCAE v5.0 will be assessed from Day 1 of study treatment through 30-days past the last study treatment per patient, through study closure, up to 24 months.

• Overall Response Rate

  ORR is assessed from Day 1 of treatment to study closure, up to 24 months. ORR is calculated by adding the Complete Responses (CR) with the Partial Responses (PR), based on RECIST v1.1, recorded at each disease evaluation for each patient.

• Disease Control Rate

  DCR is assessed from Day 1 of treatment to study closure, up to 24 months. DCR is calculated by adding the Complete Responses, Partial Responses and Stable Disease, based on RECIST v1.1, recorded at each disease evaluation for each patient.

• Duration of Response

  DOR is assessed from Day 1 of treatment to study closure, up to 24 months. DOR is calculated for patients who achieve a CR or PR, as the number of days from the date of response to the date of progression, or death, due to any cause.

• Overall Survival

  Overall Survival is assessed from date of registration to study closure, up to 24 months. Overall Survival is calculated as the number of days from date of registration to date of death due to any cause.

Other Outcomes (8)

• Evaluate Plasma Hyaluronan (HA) levels

  Plasma Hyaluronan (HA) levels are measured in blood samples taken at Day 1 of every treatment cycle (1 cycle = 3 weeks), during each patient's study treatment, with data from these samples assessed until study closure, up to 24 months.

• Evaluate immunological biomarkers using flow cytometry in tumor tissue samples

  Immunological biomarkers using flow cytometry are measured in tumor tissue samples taken at 3 timepoints during each patient's study treatment, with data from these samples assessed until study closure, up to 24 months.

• Evaluate immunological biomarkers--T-cell receptor (TCR) sequencing in tumor tissue samples

  Immunological biomarkers of T-cell receptor (TCR) sequencing are measured in tumor tissue samples taken at 3 timepoints during each patient's study treatment, with data from these samples assessed until study closure, up to 24 months.

Study Arms (1)

PEGPH20 plus Pembrolizumab

EXPERIMENTAL

All patients will receive treatment with PEGPH20 3 micrograms/kg IV weekly x 3, and pembrolizumab 200 mg IV every 3 weeks, in 3-week cycles.

Drug: PEGPH20; Biological: Pembrolizumab

Interventions

PEGPH20 DRUG

PEGPH20 is a PEGylated, neutral-pH-active human hyaluronidase PH20 produced by recombinant DNA technology

PEGPH20 plus Pembrolizumab

Pembrolizumab BIOLOGICAL

Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2

Also known as: Keytruda, MK-3475

PEGPH20 plus Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Histologically confirmed metastatic pancreatic ductal adenocarcinoma, via archived or fresh core biopsy of either primary tumor or metastatic site.
• Available tumor tissue (formalin-fixed paraffin-embedded \[FFPE\] block preferred) with enough tumor to make a minimum of 5-10 unstained, consecutive FFPE slides (10 slides are preferred) of 1 archival block that meets specific tissue sample requirements. Archived or fresh tissue from the primary lesion or a metastatic lesion is required. Note: Fine needle aspirates or brushing biopsies will not be acceptable. This tumor tissue requirement is for the determination of the HA-high or -low expression status.
• years of age on day of signing informed consent.
• Have measurable metastatic disease based on RECIST 1.1.
• Life expectancy ≥ 12 weeks.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Received no more than 2 prior lines of systemic therapy for metastatic disease (1 or 2 prior lines of therapy for metastatic disease are allowed)
• Be willing to provide tumor tissue from newly obtained tumor cores or excisional biopsy for research purposes. Newly-obtained is defined as a specimen obtained within 2 weeks (14 days) prior to initiation of treatment on Day 1.
• Be willing to provide tumor tissue from tumor biopsy after 6 weeks of treatment (mandatory, if safe and feasible), and at the time of tumor progression (optional, if safe and feasible). Note: Fine needle aspirates or brushing biopsies will not be acceptable.
• Demonstrate adequate organ function, all screening labs should be performed within 14 days of treatment initiation.
• Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 2 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (equivalent of \> 20 mg of hydrocortisone per day) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active tuberculosis (TB).
• Hypersensitivity to pembrolizumab or any of its excipients.
• Known allergy to PEGPH20 (hyaluronidase).
• Current use of megestrol acetate (use within 10 days of Day 1).
• Contraindication to heparin as per institutional guidelines.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• 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), or documented history of clinically severe autoimmune disease (e.g., colitis, Crohns' disease)\*. 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 known history of, or any evidence of active, non-infectious pneumonitis.

Sponsors & Collaborators

• Pancreatic Cancer Research Team: lead
• Merck Sharp & Dohme LLC: collaborator
• Halozyme Therapeutics: collaborator
• University of Washington: collaborator

Study Sites (5)

Banner Health - MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

NOT YET RECRUITING

Cedars Sinai Medical Center

Los Angeles, California, 80048, United States

NOT YET RECRUITING

Rutgers - Cancer Institute of New Jersey (CINJ)

New Brunswick, New Jersey, 08901, United States

ACTIVE NOT RECRUITING

University of Washington--Seattle Cancer Care Alliance

Seattle, Washington, 98101, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Related Publications (2)

• Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. doi: 10.1056/NEJMoa1500596. Epub 2015 May 30.

  PMID: 26028255 BACKGROUND

• 46. Le DT, Uram JN, Wang H, et al. PD-1 blockade in mismatch repair deficient non-colorectal gastrointestinal cancers. J Clin Oncol . 2016. 34 (suppl 4S; abstr 195).

  BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasms; Adenocarcinoma

Interventions

PEGPH20; pembrolizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Gabriella Chiorean, MD

  Seattle Cancer Care Alliance--University of Washington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Stoll-Dastice, MS

CONTACT

206-816-4239; amys@crab.org

Stephanie Edwards

CONTACT

206-652-4452; stephe@crab.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single Treatment Arm for Second-Line treatment of Specific sub-set (HA high) of advanced pancreatic cancer patients

Study Record Dates

• First Submitted: July 23, 2018
• First Posted: August 16, 2018
• Study Start: May 1, 2019
• Primary Completion: October 1, 2020
• Study Completion: January 1, 2021
• Last Updated: May 7, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)