Study investigating PEGylated Recombinant Human Hyaluronidase (PEGPH20) in previously untreated patients with pancreatic cancer that have high levels of hyaluronan. The study has two groups: all patients will be treated with nab-Paclitaxel plus Gemcitabine. In addition, one group will receive PEGPH20 and the other group will receive an inactive substance. Neither the patient nor the doctor will know the treatment group in which the patient has been randomly assigned to.

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2015-004068-13-LV
• Date of registration: 16/02/2016
• Prospective Registration: Yes
• Primary sponsor: Halozyme, Inc.
• Public title: Study investigating PEGylated Recombinant Human Hyaluronidase (PEGPH20) in previously untreated patients with pancreatic cancer that have high levels of hyaluronan. The study has two groups: all patients will be treated with nab-Paclitaxel plus Gemcitabine. In addition, one group will receive PEGPH20 and the other group will receive an inactive substance. Neither the patient nor the doctor will know the treatment group in which the patient has been randomly assigned to.
• Scientific title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) in Combination With nab-Paclitaxel Plus Gemcitabine Compared With Placebo Plus nab-Paclitaxel and Gemcitabine in Subjects with Hyaluronan-High Stage IV Previously Untreated Pancreatic Ductal Adenocarcinoma
• Date of first enrolment: 02/03/2016
• Target sample size: 420
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004068-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Brazil, Canada, China, Croatia, Czech Republic, Denmark, Estonia, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Mexico, Netherlands, Poland, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Halozyme Study Information
• Affiliation: Halozyme, Inc.

• Name: Halozyme Study Information
• Affiliation: Halozyme, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed, written Institutional Review Board/Ethics Committee approved Informed Consent Form (ICF).
2. Stage IV PDA with histological or cytological confirmation of PDA
3. Subjects must be determined to be HA-high based on archived or fresh tumor core biopsy or sample obtained after the subject has documented
metastatic disease. Biopsies/samples must meet the following requirements:
a. Pancreas tumor biopsies/samples obtained on or after the date that metastatic disease is documented or tumor biopsies/samples from a
metastatic lesion are acceptable.
b. Tumor biopsies or samples must meet the requirements provided in the Study Laboratory Manual with regard to tumor tissue architecture.
Note: cytology samples from fine needle aspirates without maintained tissue architecture or brushing biopsies are not acceptable.
c. Tumor tissue (formalin-fixed paraffin-embedded [FFPE] block preferred) must include enough tumor to make a minimum of 5-10
unstained, consecutive FFPE slides (10 slides are preferred) of 1 archival block that meet specific tissue sample requirements (see Study
Laboratory Manual). Radiographic confirmation.
4. Of Stage IV PDA with at least 1 tumor metastasis measurable on CT scan and/or MRI per RECIST version 1.1 criteria, excluding the primary
pancreatic lesion.
5. If a subject has had adjuvant/neoadjuvant therapy and/or therapy for locally advanced disease (chemotherapy for non-metastatic pancreatic
cancer in combination with or without radiation therapy), tumor recurrence or disease progression must have occurred no sooner than 6
months after completing the last dose of the aforementioned therapies, provided all toxicities have returned to baseline or = Grade 1.
6. Eastern Cooperative Oncology Group Performance Status of 0 or 1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 189
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 231

Exclusion criteria:
1. Clinical evidence of DVT, PE or other known TE event present during the screening period.
2. Previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease.
a. Palliative radiotherapy for pain control of metastatic bone lesions is allowed.
3. Known central nervous system involvement or brain metastases.
4. New York Heart Association Class III or IV cardiac disease or myocardial infarction within the past 12 months.
5. History of cerebrovascular accident or transient ischemic attack.
6. Clinically significant pre-existing carotid artery disease.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Hyaluronan-High Stage IV Previously Untreated Pancreatic Ductal Adenocarcinoma
MedDRA version: 20.0 Level: LLT Classification code 10007050 Term: Cancer System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: PEGylated Recombinant Human Hyaluronidase
Product Code: PEGPH20
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Proposed INN currently under review: pegvorhyaluronidase alfa
CAS Number: 1620390-06-8
Current Sponsor code: PEGPH20
Other descriptive name: PEGylated Recombinant Human Hyaluronidase
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.30-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: ABRAXANE
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: Paclitaxel bound to human albumin
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: Gemcitabine 38 mg/ml Concentrate for Solution for Infusion
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: gemcitabine hydrochloride
CAS Number: 122111-03-9
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 38-

Trade Name: Gemcitabine 38 mg/ml Concentrate for Solution for Infusion

Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Gemcitabine hydrochloride
CAS Number: 122111-03-9
Other descriptive name: GEMCITABINE HYDROCHLORIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentra

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Final PFS will be conducted at the interim when a pre-specified number of PFS events have occurred. Final OS analysis will be conducted at the end of the study.

During long-term follow-up information on the subject's survival and subsequent anticancer therapy will be obtained by the site monthly until
the subject dies, is lost to follow-up, or withdraws consent. Subjects will be censored for OS at the time of the last "known alive" contact. The OS
analysis will be conducted at the end of the study.

Secondary Objective: • To determine the objective response rate (ORR) and duration of response (DOR) of PAG treatment, compared with AG treatment, in subjects with HA-high Stage IV previously untreated PDA

• To assess the safety and tolerability of PAG treatment in subjects with HA-high Stage IV previously untreated PDA

Primary end point(s): • Progression-free survival
• Overall survival

Main Objective: • To determine the PFS benefit of PEGPH20 combined with nab-paclitaxel (NAB) plus gemcitabine (GEM) (PAG treatment), compared with placebo plus NAB/GEM (AG treatment), in subjects with hyaluronan (HA)-high Stage IV previously untreated pancreatic ductal adenocarcinoma (PDA)

• To determine the overall survival (OS) benefit of PAG treatment, compared with AG treatment, in subjects with HA-high Stage IV previously untreated PDA

Secondary Outcome(s)

Secondary end point(s): • Objective response rate
• Duration of response
• Incidence of AEs, changes in clinical safety laboratory values, and changes in cardiovascular parameters (electrocardiogram [ECG] and vital signs)

Timepoint(s) of evaluation of this end point: Refer to protocol for information.

Secondary ID(s)

HALO-109-301

NCT02715804

Source(s) of Monetary Support

Halozyme, Inc.

Ethics review

Status: Approved
Approval date:
Contact: