Clinical trial NCT01453153: Study of Gemcitabine + PEGPH20 vs Gemcitabine Alone in Stage IV Previously Untreated Pancreatic Cancer
Official title: A Phase 1b/2 Multicenter, International, Randomized, Double Blind, Placebo-Controlled, Study of Gemcitabine Combined With PEGPH20 Compared to Gemcitabine Combined With Placebo in Patients With Stage IV Previously Untreated Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Stage IV Pancreatic Cancer
Keywords: pancreatic
Cancer
Stage IV
untreated
Lead sponsor: Halozyme Therapeutics
Sponsor class: INDUSTRY
First posted: 2011-10-17
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: PEGPH20 is a PEGylated version of human recombinant PH20 hyaluronidase that, in preclinical studies, has been shown to remove HA from the extracellular matrix surrounding tumor cells by depolymerizing this substrate. 87% of pancreatic ductal adenocarcinomas (PDA) overexpress HA. PDA tumor tissue may be especially sensitive to the HA-degradation properties of PEGPH20 and thus more responsive to the cytotoxic effects of a given dose of gemcitabine. Modifying the extracellular environment to increase the penetration and efficacy of anti-cancer agents represents a novel approach to treating pancreatic cancer and may provide important therapeutic outcomes in patients with Stage IV Previously Untreated Pancreatic Cancer.

This Phase 1B/2 study will assess safety, tolerability, treatment effect, and various PK/PD endpoints.

Eligibility criteria: Key Inclusion Criteria:

* 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

Key Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With a Dose-limiting Toxicity (DLT)
timeFrame: first 4 weeks of Cycle 1
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: first 4 weeks of Cycle 1
Secondary outcomes:
measure: Observed Maximum Plasma Concentration (Cmax) Following Single PEGPH20 Doses
timeFrame: 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)
measure: Cmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
timeFrame: 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)
measure: Last Measurable Observed Plasma Concentration (Cmin) Following Single PEGPH20 Doses
timeFrame: 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)
measure: Cmin Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
timeFrame: 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)
measure: Time to Reach Cmax (Tmax) Following Single PEGPH20 Doses
timeFrame: 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)
measure: Tmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
timeFrame: 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)
measure: Apparent Half-life (t1/2) Following Single PEGPH20 Doses
timeFrame: 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)
measure: t1/2 Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
timeFrame: 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)
measure: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Measurable Plasma Concentration (AUC0-T) Following Single PEGPH20 Doses
timeFrame: 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)
measure: AUC0-T Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
timeFrame: 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)
measure: Plasma Hyaluronan (HA) Concentration at Baseline and After PEGPH20 Administration
timeFrame: Baseline; post-Baseline (average treatment duration of 94.6 days)
measure: H-scores, as an Assessment of HA Staining Changes in Tumor Biopsies
timeFrame: Screening; Cycle 1 Week 7
measure: Percent Change in in the Maximum Standardized Uptake Value (SUVmax), as an Assessment of Total Lesion Metabolic Activity
timeFrame: Baseline; up to 32 weeks for each individual participant (end of Cycle 7)
measure: Mean Volume Transfer Constant (Ktrans) for Scans Across Tissue Sites
timeFrame: Baseline; 24 hours hours; end of Cycle 1 (Week 7)
measure: Mean Extravascular-Extracellular Volume Fraction (Ve) for Scans Across Tissue Sites
timeFrame: Baseline; 24 hours hours; end of Cycle 1 (Week 7)
measure: Number of Participants With the Indicated Best Response, Per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1
timeFrame: up to approximately 2 years 4 months
measure: Objective Response Rate
timeFrame: up to approximately 2 years 4 months
measure: Disease Control Rate
timeFrame: up to approximately 2 years 4 months
measure: Progression-free Survival (PFS)
timeFrame: from the first dose of PEGH20 until objective tumor progression or death (up to approximately 2 years 4 months)
measure: Overall Survival
timeFrame: from the time of the first dose of PEGPH20 until death (up to approximately 2 years 4 months)
measure: Change From Baseline in Carbohydrate Antigen 19-9 or Sialylated Lewis(a) Antigen (CA19-9)
timeFrame: up to the end of Cycle 10 (up to Week 44)
measure: Change From Baseline in CA19-9 in Participants With a Baseline Value >=59 U/ml
timeFrame: up to the end of Cycle 10 (up to Week 44)
measure: Change From Baseline in CA19-9 in Participants Classified as Responders and Non-responders
timeFrame: up to the end of Cycle 10 (up to Week 44)
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Newark
country: United States
facility: UMDNJ - New Jersey Medical School
state: New Jersey
city: New Hyde Park
country: United States
facility: NSLIJ Health System, Monter Cancer Center
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Oncology Center
city: Moscow
country: Russian Federation
facility: Russian Oncological Research Center n.a. N.N. Blokhin
city: Obninsk
country: Russian Federation
facility: Medical Radiological Research Center
city: Omsk
country: Russian Federation
facility: Omsk Regional Budget Medical Institution
Study officials:
affiliation: Halozyme Therapeutics
name: Joy H Zhu, MD, PhD
role: STUDY_DIRECTOR
References: