Study of PEGPH20 With Cisplatin (CIS) and Gemcitabine (GEM); PEGPH20 With Atezolizumab (ATEZO), CIS, and GEM; and CIS and GEM Alone in Participants With Previously Untreated, Unresectable, Locally Advanced, or Metastatic Intrahepatic and Extrahepatic Cholangiocarcinoma and Gallbladder Adenocarcinoma
Condition: Cholangiocarcinoma Non-resectable; Cholangiocarcinoma, Intrahepatic; Cholangiocarcinoma, Extrahepatic; Gallbladder Adenocarcinoma
MeSH terms: Adenocarcinoma; Cholangiocarcinoma
Intervention: PEGPH20; CIS; GEM; Atezolizumab
Intervention description: PEGPH20 will be administered as per the schedule specified in the respective arms.; CIS will be administered as per the schedule specified in the respective arms.; GEM will be administered as per the schedule specified in the respective arms.; Atezolizumab will be administered as per the schedule specified in the respective arms.
Intervention MeSH terms: Atezolizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 85.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Extrahepatic Cholangiocarcinoma; Intrahepatic Cholangiocarcinoma; Gallbladder Adenocarcinoma; PEGylated Recombinant Human Hyaluronidase; PEGylated Recombinant Human Hyaluronidase with atezolizumab

Summary:

      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).
    

Eligibility criteria:

        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 (for example, 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 (for example, primary biliary
                  cholangitis, primary sclerosing cholangitis, history of immune-mediated
                  cholangitis);

                  Participants with cholangitis attributed to infectious etiology (for example,
                  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