Purpose

The study is being conducted to assess the safety and tolerability of (1) PEGPH20 in combination with CIS and GEM (PEGCISGEM), and (2) PEGPH20 in combination with CIS, GEM, and atezolizumab (PEGCISGEMATEZO) compared with (3) cisplatin and gemcitabine (CISGEM).

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

For both portions of the study, participants must satisfy all of the following inclusion criteria to be enrolled in the study:

- Written Institutional Review Board/Ethics Committee-approved informed consent form (ICF), signed by participant or legally authorized representative.

- Participants must be determined to have histologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of the intra- and/or extra-hepatic bile ducts and/or gallbladder. Participants must have sufficient tissue with architectural integrity, including tumor and associated stroma, available for retrospective biomarker testing.

- One or more lesions measurable on computed tomography (CT) scan/magnetic resonance imaging (MRI) scan per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1).

- Participants having Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.

- Life expectancy ≥3 months.

- Males and females aged ≥18 years.

- Screening clinical laboratory values within pre-determined parameters

- Female participants of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test within 7 days before Day 1 (first dose of study medication).

- For WOCBP and for men, agreement to use a highly effective contraceptive method from the time of screening throughout the study until 5 months (WOCBP) or 6 months (men) after administration of the last dose of any study medication. Highly effective contraceptive methods consist of prior sterilization, intrauterine device (IUD), intrauterine hormone releasing system (IUS), oral or injectable contraceptives, barrier methods, and/or true sexual abstinence.

Exclusion Criteria

Participants are ineligible for enrollment if they meet any of the following exclusion criteria:

- Clinical evidence of deep vein thrombosis or pulmonary embolism present during the screening period

- New York Heart Association Class III or IV cardiac disease, atrial fibrillation, unstable angina, or myocardial infarction within the past 12 months before screening.

- Participants with known brain metastases

- History of cerebrovascular accident or transient ischemic attack

- History of active bleeding within the last 3 months prior to screening requiring transfusion.

- Participants must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for treatment of metastatic or locally advanced disease.

- Intolerance to non-steroidal anti-inflammatory drugs (NSAIDs).

- Active hepatitis B virus (HBV) infection, defined as having a positive hepatitis B surface antigen (HBsAg) test at screening

- Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test at screening

- History of:

1. Idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

2. Or known cases of hepatobiliary diseases (e.g., primary biliary cholangitis, primary sclerosing cholangitis, history of immune-mediated cholangitis);

Participants with cholangitis attributed to infectious etiology (e.g., ascending cholangitis, bacterial cholangitis) are eligible if the infection has been fully resolved prior to the screening visit.

3. Or known cases of drug-induced hepatobiliary toxicities.

- Active or history of autoimmune diseases

- Uncontrolled hypercalcemia

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Run-in Portion Arm 1: PEGCISGEM
Approximately 6 participants will receive 3.0 micrograms per kilogram (μg/kg) PEGPH20 on Days 1, 8, and 15 in combination with 25 milligrams per meter squared (mg/m^2) of CIS plus 1000 mg/m^2 of GEM administered on Days 2 and 9 of each 21-day cycle by intravenous (IV) infusion.
  • Drug: PEGPH20
    PEGPH20 will be administered as per the schedule specified in the respective arms.
  • Drug: CIS
    CIS will be administered as per the schedule specified in the respective arms.
  • Drug: GEM
    GEM will be administered as per the schedule specified in the respective arms.
Experimental
Run-in Portion Arm 2: PEGCISGEMATEZO
After the 6 participants in Arm 1 are treated for at least 1 cycle without significant toxicities, 6 additional participants will be enrolled into Arm 2 of the Run-in Portion of the study. Participants will receive 3.0 µg/kg PEGPH20 on Days 1, 8, and 15 in combination with 1200 mg atezolizumab (ATEZO) (administered 1 to 3 hours after PEGPH20 on Day 1 of each 21-day cycle) plus 25 mg/m^2 of CIS and 1000 mg/m^2 GEM on Days 2 and 9 of each 21-day cycle by IV infusion. PEGPH20 dose reduction to a lower dose of 2.2 µg/kg or 1.6 µg/kg will be performed if necessary.
  • Drug: PEGPH20
    PEGPH20 will be administered as per the schedule specified in the respective arms.
  • Drug: CIS
    CIS will be administered as per the schedule specified in the respective arms.
  • Drug: GEM
    GEM will be administered as per the schedule specified in the respective arms.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arms.
Experimental
Expansion Portion Arm 1: PEGCISGEM
Participants will receive 3.0 µg/kg PEGPH20 on Days 1, 8, and 15 in combination with 25 mg/m^2 CIS and 1000 mg/m^2 GEM on Days 2 and 9 of each 21-day cycle by IV infusion.
  • Drug: PEGPH20
    PEGPH20 will be administered as per the schedule specified in the respective arms.
  • Drug: CIS
    CIS will be administered as per the schedule specified in the respective arms.
  • Drug: GEM
    GEM will be administered as per the schedule specified in the respective arms.
Experimental
Expansion Portion Arm 2: PEGCISGEMATEZO
Participants will receive 3.0 µg/kg PEGPH20 on Days 1, 8, and 15 in combination with 1200 mg ATEZO (administered 1 to 3 hours after PEGPH20 on Day 1of each 21-day cycle) plus 25 mg/m^2 of CIS and 1000 mg/m^2 GEM on Days 2 and 9 of each 21-day cycle by IV infusion.
  • Drug: PEGPH20
    PEGPH20 will be administered as per the schedule specified in the respective arms.
  • Drug: CIS
    CIS will be administered as per the schedule specified in the respective arms.
  • Drug: GEM
    GEM will be administered as per the schedule specified in the respective arms.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arms.
Experimental
Expansion Portion Arm 3: PEGCISGEMATEZO Modified
Participants will receive 3.0 µg/kg PEGPH20 on Days 1, 4, 8, 11, 15 and 18 in Cycle 1 and on Days 1, 8, and 15 from Cycle 2 onwards in combination with 1200 mg ATEZO (administered 1 to 3 hours after PEGPH20 on Day 1of each 21-day cycle) plus 25 mg/m^2 of CIS and 1000 mg/m^2 GEM on Days 2 and 9 of each 21-day cycle by IV infusion.
  • Drug: PEGPH20
    PEGPH20 will be administered as per the schedule specified in the respective arms.
  • Drug: CIS
    CIS will be administered as per the schedule specified in the respective arms.
  • Drug: GEM
    GEM will be administered as per the schedule specified in the respective arms.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arms.
Active Comparator
Expansion Portion Arm 4: CISGEM
Participants will receive 25 mg/m^2 CIS and 1000 mg/m^2 GEM on Days 1 and 8 of each 21-day cycle by IV infusion.
  • Drug: CIS
    CIS will be administered as per the schedule specified in the respective arms.
  • Drug: GEM
    GEM will be administered as per the schedule specified in the respective arms.

Recruiting Locations

UT Health Cancer Center
San Antonio, Texas 78229
Contact:
Jennifer Moseley
moseleyj@uthscsa.edu

More Details

NCT ID
NCT03267940
Status
Recruiting
Sponsor
Halozyme Therapeutics

Study Contact

Halozyme Study Information
844-855 HALO (4256)
Medinfo@halozyme.com

Detailed Description

The study will have a Run-in portion and an Expansion portion. The Run-in portion will be used to evaluate the safety profile of the PEGCISGEM and PEGCISGEMATEZO treatments prior to evaluating the efficacy and safety of PEGCISGEM and PEGCISGEMATEZO treatments compared with CISGEM treatment in the Expansion portion of the study. Treatment in both portions of the study will continue until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.