Stage IV Pancreatic CancerPhase 1/2NCT01453153
Study of Gemcitabine + PEGPH20 vs Gemcitabine Alone in Stage IV Previously Untreated Pancreatic Cancer
A Phase 1/2 study testing Gemcitabine and PEGPH20 in people with Stage IV Pancreatic Cancer, run by Halozyme Therapeutics at 12 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IV Pancreatic Cancer
- What is being tested?
- Gemcitabine and PEGPH20
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 12 sitesin 2 countries
- Study dates
- Sep 2011to May 2015
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
United States8 sites
Highlands Oncology Group
Fayetteville, Arkansas, 72707
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
NSLIJ Health System, Monter Cancer Center
New Hyde Park, New York, 11040
Mount Sinai School of Medicine
New York, New York, 10029
UMDNJ - New Jersey Medical School
Newark, New Jersey, 07103
California Pacific Medical Center
San Francisco, California, 94120
Seattle Cancer Care Alliance
Seattle, Washington, 90108
SUNY Upstate Medical University
Syracuse, New York, 13210
Russia4 sites
Chelyabinsk Regional Clinical Oncology Center
Chelyabinsk
Russian Oncological Research Center n.a. N.N. Blokhin
Moscow
Medical Radiological Research Center
Obninsk
Omsk Regional Budget Medical Institution
Omsk
About this study
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
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.
Read the 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.
- Conditions
- Stage IV Pancreatic Cancer
- Being tested
- Gemcitabine, PEGPH20, Placebo
- Keywords
- pancreatic, Cancer, Stage IV, untreated
- Medical subject headings
- Pancreatic Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Also called Gemzar
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)
PEGPH20Drug
Also called PEGylated Recombinant Human Hyaluronidase
(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
PlaceboDrug
Also called Saline
(Cycle 1: 7 weeks on treatment/1 week off treatment; Cycle 2+: 3 Weeks on treatment/1 week off treatment).
| Study group | Role | What they receive |
|---|---|---|
| Gemcitabine | Active comparator | Gemcitabine + Placebo Receives: Drug: Gemcitabine; Drug: Placebo |
| PEGPH20 | Experimental | PEGPH20+Gemcitabine Receives: Drug: Gemcitabine; Drug: PEGPH20 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: first 4 weeks of Cycle 1
Secondary outcomes (23)
Observed Maximum Plasma Concentration (Cmax) Following Single PEGPH20 Doses
Cmax is defined as the observed maximum plasma concentration after the first dose. Blood samples were collected for pharmacokinetic assessment.
Measured: 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
Cmax is defined as the observed maximum plasma concentration after the first dose. Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional.
Measured: 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
Blood samples were collected for pharmacokinetic assessment.
Measured: 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
Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional.
Measured: 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
Blood samples were collected for pharmacokinetic assessment.
Measured: 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)
Tmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional.
Measured: 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)
Apparent Half-life (t1/2) Following Single PEGPH20 Doses
The apparent half-life calculated by ln(2)/λ, where λ was the rate constant for the log-linear portion of the terminal phase. A minimum of 3 values in the postdistribution phase of the plasma concentration-time curve were required for calculation of λ. Blood samples were collected for pharmacokinetic assessment. t1/2 is expressed as harmonic mean and pseudo standard deviation.
Measured: 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)
t1/2 Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
The apparent half-life calculated by ln(2)/λ, where λ was the rate constant for the log-linear portion of the terminal phase. A minimum of 3 values in the postdistribution phase of the plasma concentration-time curve were required for calculation of λ. Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional. t1/2 is expressed as harmonic mean and pseudo standard deviation.
Measured: 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)
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
Blood samples were collected for pharmacokinetic assessment. AUC0-T was calculated by the linear trapezoidal rule.
Measured: 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)
AUC0-T Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional. AUC0-T was calculated by the linear trapezoidal rule.
Measured: 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)
Plasma Hyaluronan (HA) Concentration at Baseline and After PEGPH20 Administration
The pharmacodynamic activity of PEGPH20 was evaluated by measuring plasma concentrations of HA after PEGPH20 dosing. Peak HA concentrations are the highest concentrations measured after a single dose of PEGPH20. HA samples were collected in Cycle 1 at the following time points: 1) Week 1/Day 1 (first visit) and Week 4 (first visit): predose and 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing (24-hour sample optional for Week 4); 2) all other visits in Cycle 1: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given). HA samples were collected in Cycles 2+ at the following time points: Week 3 of each cycle pre-PEGPH20 dose and 1 to 2 hours post-PEGPH20 dose.
Measured: Baseline; post-Baseline (average treatment duration of 94.6 days)
H-scores, as an Assessment of HA Staining Changes in Tumor Biopsies
An H-score approach methodology was developed and used to analyze staining in the tumor pericellular regions and the stroma separately. The H-score calculation was the sum of the products of the percentage of positive staining areas and the staining intensity (0, 1, 2 or 3), and ranged from 0 to 300. For example: [90% * 1 (weak)] + [10% * 2 (moderate)] + [0% * 3 (strong)] = 110. A score of 0 represents the absence of expression, and an H-score of 300 represents maximum expression. A larger decrease in H-score correlated with a greater target engagement of PEGPH20. As HA is a secreted protein, the scoring was performed in the immediate areas surrounding tumor (pericellular areas) as well as in stroma.
Measured: Screening; Cycle 1 Week 7
Percent Change in in the Maximum Standardized Uptake Value (SUVmax), as an Assessment of Total Lesion Metabolic Activity
PEGPH20's effect on the metabolic activities of the tumor was assessed as the percent change in SUVmax (a measure of total lesion metabolic activity) using fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT). Assessment was done for the entire cohort of participants, not per treatment group.
Measured: Baseline; up to 32 weeks for each individual participant (end of Cycle 7)
Mean Volume Transfer Constant (Ktrans) for Scans Across Tissue Sites
Dynamic control enhanced-magnetic resonance imaging (DCE-MRI) provides a measure of the exchange of small-molecule contrast agents between the intracellular and extracellular spaces. Using a 2-compartment pharmacokinetic model, an estimate of tissue (tumor) perfusion can be obtained by determining the exchange rate constant (Ktrans) of contrast exchange. Ktrans is defined as the volume transfer constant between extravascular/extracellular space to plasma space and is a measure of blood flow, vascular permeability, or both. Mean Ktrans values across scan sites are reported per participant. DCE-MRI was performed before the first dosing visit (Week 1/Day 1), 24 hours after the first dose of PEGPH20 in Cycle 1, and 24 hours after the last dose of PEGPH20 in Cycle 1 (Week 7). Assessment was done for the entire cohort of participants, not per treatment group.
Measured: Baseline; 24 hours hours; end of Cycle 1 (Week 7)
Mean Extravascular-Extracellular Volume Fraction (Ve) for Scans Across Tissue Sites
DCE-MRI provides a measure of the exchange of small-molecule contrast agents between the intracellular and extracellular spaces. Ve is defined as the extravascular-extracellular volume fraction and is a measure of extracellular, extravascular space. Mean Ve values across scan sites are reported per participant. DCE-MRI was performed before the first dosing visit (Week 1/Day 1), 24 hours after the first dose of PEGPH20 in Cycle 1, and 24 hours after the last dose of PEGPH20 in Cycle 1 (Week 7). Assessment was done for the entire cohort of participants, not per treatment group.
Measured: Baseline; 24 hours hours; end of Cycle 1 (Week 7)
Number of Participants With the Indicated Best Response, Per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1
Target lesions (TLs), complete response (CR): Disappearance of all TLs. Partial response (PR): >=30% decrease in the sum of diameters of TLs, referencing baseline sums. Progressive disease (PD): >= 20% increase in the sum of diameters of TLs, referencing the smallest sum (including baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of >=5 mm. (The appearance of >=1 new lesions is considered progression.) Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient to qualify for PD, referencing the smallest sum diameters. For nontarget lesions (NTLs), CR: Disappearance of all NTLs and normalization of tumor marker level. All lymph nodes must be nonpathological in size (short axis <10 mm). Incomplete response/SD: Persistence of >=1 NTLs and/or maintenance of tumor marker level above normal limits. PD: Unequivocal progression of existing NTLs. (The appearance of >=1 new lesions is considered progression.)
Measured: up to approximately 2 years 4 months
Objective Response Rate
Objective Response Rate is defined as the number of participants with a complete response plus the number of participants with a partial response, per RECIST, Version 1.1. For TLs, CR: Disappearance of all TLs. PR: >=30% decrease in the sum of diameters of TLs, referencing baseline sums. For NTLs, CR: Disappearance of all NTLs and normalization of tumor marker level. All lymph nodes must be nonpathological in size (short axis <10 mm). Incomplete response/SD: Persistence of >=1 NTLs and/or maintenance of tumor marker level above normal limits.
Measured: up to approximately 2 years 4 months
Disease Control Rate
Disease Control Rate is defined as the sum of the number of participants with a complete response, the number of participants with a partial response, and the number of participants with stable disease per RECIST, Version 1.1. For TLs, CR: Disappearance of all TLs. PR: >=30% decrease in the sum of diameters of TLs, referencing baseline sums. SD: Neither sufficient shrinkage to qualify for PR nor sufficient to qualify for PD, referencing the smallest sum diameters. For NTLs, CR: Disappearance of all NTLs and normalization of tumor marker level. All lymph nodes must be nonpathological in size (short axis <10 mm). Incomplete response/SD: Persistence of >=1 NTLs and/or maintenance of tumor marker level above normal limits.
Measured: up to approximately 2 years 4 months
Progression-free Survival (PFS)
PFS duration was defined as the time from the first dose of PEGPH20 until objective tumor progression or death. Per RECIST, Version 1.1, for the evaluation of target lesions, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters. Note: the appearance of 1 or more new lesions is also considered progression. For the evaluation of nontarget lesions, progressive disease is defined as the unequivocal progression of existing nontarget lesions. Note: The appearance of 1 or more new lesions is also considered progression.
Measured: from the first dose of PEGH20 until objective tumor progression or death (up to approximately 2 years 4 months)
Overall Survival
Overall survival was defined as the time from the time of the first dose of PEGPH20 until death.
Measured: from the time of the first dose of PEGPH20 until death (up to approximately 2 years 4 months)
Change From Baseline in Carbohydrate Antigen 19-9 or Sialylated Lewis(a) Antigen (CA19-9)
CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations.
Measured: up to the end of Cycle 10 (up to Week 44)
Change From Baseline in CA19-9 in Participants With a Baseline Value >=59 U/ml
CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations.
Measured: up to the end of Cycle 10 (up to Week 44)
Change From Baseline in CA19-9 in Participants Classified as Responders and Non-responders
CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations. Responders are defined as participants who had a complete response or partial response, and non-responders are defined as participants who had stable disease, progressive disease, or an unknown tumor response, per RECIST, Version 1.1.
Measured: up to the end of Cycle 10 (up to Week 44)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2011 (estimated)
- Study startSep 2011
- Primary completionFeb 2014
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Stage IV Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Halozyme Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Joy H Zhu, MD, PhD, Study director, Halozyme Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01453153
- Sponsor's protocol ID
- Halo-109-201
- Status last verified
- Oct 2018
- First submitted
- 13 Oct 2011
- Last updated
- 30 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01453153
- Acronym / sponsor ID
- Halo-109-201
- Conditions
- Stage IV Pancreatic Cancer
- Keywords
- pancreatic, Cancer, Stage IV, untreated
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Halozyme TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Sep 2011
- Primary completion
- Feb 2014 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 17 Oct 2011 (estimated)
- Results
- Posted 30 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gemcitabine | Active comparator | Drug: Gemcitabine, Drug: PlaceboGemcitabine + Placebo |
| PEGPH20 | Experimental | Drug: Gemcitabine, Drug: PEGPH20PEGPH20+Gemcitabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GemcitabineAlso: Gemzar1000 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) | Drug | Gemcitabine, PEGPH20 |
| PEGPH20Also: PEGylated Recombinant Human Hyaluronidase(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 | Drug | PEGPH20 |
| PlaceboAlso: Saline(Cycle 1: 7 weeks on treatment/1 week off treatment; Cycle 2+: 3 Weeks on treatment/1 week off treatment). | Drug | Gemcitabine |
Primary outcome
Number of Participants With a Dose-limiting Toxicity (DLT)
Time frame: first 4 weeks of Cycle 1
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.
Recommended Phase 2 Dose (RP2D)
Time frame: first 4 weeks of Cycle 1
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.
23 secondary outcomes
Observed Maximum Plasma Concentration (Cmax) Following Single PEGPH20 Doses
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Tmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Time frame: 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)
Apparent Half-life (t1/2) Following Single PEGPH20 Doses
Time frame: 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)
t1/2 Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Time frame: 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)
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
Time frame: 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)
AUC0-T Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Time frame: 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)
Plasma Hyaluronan (HA) Concentration at Baseline and After PEGPH20 Administration
Time frame: Baseline; post-Baseline (average treatment duration of 94.6 days)
H-scores, as an Assessment of HA Staining Changes in Tumor Biopsies
Time frame: Screening; Cycle 1 Week 7
Percent Change in in the Maximum Standardized Uptake Value (SUVmax), as an Assessment of Total Lesion Metabolic Activity
Time frame: Baseline; up to 32 weeks for each individual participant (end of Cycle 7)
Mean Volume Transfer Constant (Ktrans) for Scans Across Tissue Sites
Time frame: Baseline; 24 hours hours; end of Cycle 1 (Week 7)
Mean Extravascular-Extracellular Volume Fraction (Ve) for Scans Across Tissue Sites
Time frame: Baseline; 24 hours hours; end of Cycle 1 (Week 7)
Number of Participants With the Indicated Best Response, Per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1
Time frame: up to approximately 2 years 4 months
Objective Response Rate
Time frame: up to approximately 2 years 4 months
Disease Control Rate
Time frame: up to approximately 2 years 4 months
Progression-free Survival (PFS)
Time frame: from the first dose of PEGH20 until objective tumor progression or death (up to approximately 2 years 4 months)
Overall Survival
Time frame: from the time of the first dose of PEGPH20 until death (up to approximately 2 years 4 months)
Change From Baseline in Carbohydrate Antigen 19-9 or Sialylated Lewis(a) Antigen (CA19-9)
Time frame: up to the end of Cycle 10 (up to Week 44)
Change From Baseline in CA19-9 in Participants With a Baseline Value >=59 U/ml
Time frame: up to the end of Cycle 10 (up to Week 44)
Change From Baseline in CA19-9 in Participants Classified as Responders and Non-responders
Time frame: up to the end of Cycle 10 (up to Week 44)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joy H Zhu, MD, PhD study director
Halozyme Therapeutics
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Gemcitabine and PEGPH20 in people with Stage IV Pancreatic Cancer, run by Halozyme Therapeutics at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With a Dose-limiting Toxicity (DLT) (time frame: first 4 weeks of Cycle 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2018.