Study of Gemcitabine + PEGPH20 vs Gemcitabine Alone in Stage IV Previously Untreated Pancreatic Cancer

NCT01453153 | Completed Phase 1 Results

• 1 other identifier: Halo-109-201
• Study Type: interventional
• Target: 28
• Locations: 2 countries
• Sites: 12

Brief Summary

Phase 1B: Open label (all patients receive PEGPH20+gemcitabine), dose escalation, safety and tolerability study to determine the safe dose of PEGPH20 to use in combination with gemcitabine in Stage IV previously untreated pancreatic cancer patients. Phase 2: Randomized, double blind study to compare the effect of overall survival of gemcitabine plus PEGPH20 vs gemcitabine plus placebo in Stage IV previously untreated pancreatic cancer patients.

Conditions

Stage IV Pancreatic Cancer

Keywords

pancreatic; Cancer; Stage IV; untreated

Outcome Measures

Primary Outcomes (2)

• Number of Participants With a Dose-limiting Toxicity (DLT)

  The safety and tolerability profile of PEGPH20 used in combination with gemcitabine was assessed by measuring the number of participants with a DLT during the dose-escalation phase of the study. A DLT was defined as any treatment-emergent National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE), Version 4.0, Grade 3 or greater event occurring within the first 4 weeks of treatment that was considered related to PEGPH20. Any PEGPH20 treatment-related AE that resulted in a drug interruption or reduction might have been considered a DLT at the Investigator's or Sponsor's discretion. Hypersensitivity/infusion reactions related to PEGPH20 dosing were not considered DLTs.

  first 4 weeks of Cycle 1

• Recommended Phase 2 Dose (RP2D)

  The safety and tolerability profile of PEGPH20 used in combination with gemcitabine was assessed by determining the RP2D, the highest dose level at which no more than 1 of 6 evaluable participants experienced a DLT in the first 4 weeks of treatment (considered a safe dose). The RP2D was determined based on review of safety and pharmacokinetic (PK) data from participants enrolled during the dose-escalation phase of the study.

  first 4 weeks of Cycle 1

Secondary Outcomes (23)

• Observed Maximum Plasma Concentration (Cmax) Following Single PEGPH20 Doses

  Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

• Cmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks

  Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

• Last Measurable Observed Plasma Concentration (Cmin) Following Single PEGPH20 Doses

  Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

• Cmin Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks

  Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

• Time to Reach Cmax (Tmax) Following Single PEGPH20 Doses

  Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

Study Arms (2)

Gemcitabine

ACTIVE COMPARATOR

Gemcitabine + Placebo

Drug: Gemcitabine; Drug: Placebo

PEGPH20

EXPERIMENTAL

PEGPH20+Gemcitabine

Drug: Gemcitabine; Drug: PEGPH20

Interventions

Gemcitabine DRUG

1000 mg/m2 given IV one time a week (Cycle 1: 7 weeks on treatment, 1 week off treatment; Cycle 2+: 3 Weeks on treatment, 1 week off treatment)

Also known as: Gemzar

Gemcitabine; PEGPH20

PEGPH20 DRUG

(Cycle 1: 7 weeks on treatment/1 week off treatment; Cycle 2+: 3 Weeks on treatment/1 week off treatment). Doses start at 1.0 mcg/kg and modified until recommended Phase 2 dose is determined. Treatment continues until occurrence of significant treatment-related toxicity, progressive disease, or discontinuation criteria are met

Also known as: PEGylated Recombinant Human Hyaluronidase

PEGPH20

Placebo DRUG

(Cycle 1: 7 weeks on treatment/1 week off treatment; Cycle 2+: 3 Weeks on treatment/1 week off treatment).

Also known as: Saline

Gemcitabine

Eligibility Criteria

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

You may qualify if:

• Patients with histologically confirmed Stage IV adenocarcinoma of the pancrease previously untreated for metastatic disease
• One or more metastatic tumors measurable on CT scan per RECIST 1.1 criteria
• Life expectancy of at least 3 months
• Signed, written IRB/EC-approved informed consent
• A negative serum pregnancy test, if female

You may not qualify if:

• Known brain metastasis
• New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 12 months
• Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy
• Known allergy to hyaluronidase
• Women currently pregnant or breast feeding

Sponsors & Collaborators

• Halozyme Therapeutics: lead

Study Sites (12)

Highlands Oncology Group

Fayetteville, Arkansas, 72707, United States

Location

California Pacific Medical Center

San Francisco, California, 94120, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

UMDNJ - New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

NSLIJ Health System, Monter Cancer Center

New Hyde Park, New York, 11040, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 90108, United States

Location

Chelyabinsk Regional Clinical Oncology Center

Chelyabinsk, Russia

Location

Russian Oncological Research Center n.a. N.N. Blokhin

Moscow, Russia

Location

Medical Radiological Research Center

Obninsk, Russia

Location

Omsk Regional Budget Medical Institution

Omsk, Russia

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasms

Interventions

Gemcitabine; PEGPH20; Sodium Chloride

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dimitrios Chondros, M.D., Chief Medical Officer
• Organization: Halozyme Therapeutics

dchondros@halozyme.com

858-794-8889

Study Officials

• Joy H Zhu, MD, PhD

  Halozyme Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2011
• First Posted: October 17, 2011
• Study Start: September 1, 2011
• Primary Completion: February 1, 2014
• Study Completion: May 1, 2015
• Last Updated: November 30, 2018
• Results First Posted: November 30, 2018

Record last verified: 2018-10

Locations

US (8); RU (4)