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

NCT ID: NCT03267940

Last Updated: 2020-02-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-02
• Study Completion Date: 2019-11-11

Brief 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).

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.

Conditions

Cholangiocarcinoma Non-resectable; Cholangiocarcinoma, Intrahepatic; Cholangiocarcinoma, Extrahepatic; Gallbladder Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Run-in Portion: PEGCISGEM

Participants will receive 3.0 micrograms per kilogram (mcg/kg) PEGPH20 on Days 1, 8, and 15 in combination with 25 milligrams per meter square (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. Treatment will continue until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity.

Group Type: EXPERIMENTAL

PEGPH20

Intervention Type: DRUG

PEGPH20 will be administered as per the schedule specified in the respective arms.

CIS

Intervention Type: DRUG

CIS will be administered as per the schedule specified in the respective arms.

GEM

Intervention Type: DRUG

GEM will be administered as per the schedule specified in the respective arms.

Run-in Portion: PEGCISGEMATEZO

After 6 participants from the PEGCISGEM arm are treated for at least 1 cycle without significant toxicities, new participants will be enrolled in this arm to receive 3.0 mcg/kg PEGPH20 on Days 1, 8, and 15 in combination with 1200 mg 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. Treatment will continue until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity.

Group Type: EXPERIMENTAL

PEGPH20

Intervention Type: DRUG

PEGPH20 will be administered as per the schedule specified in the respective arms.

CIS

Intervention Type: DRUG

CIS will be administered as per the schedule specified in the respective arms.

GEM

Intervention Type: DRUG

GEM will be administered as per the schedule specified in the respective arms.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered as per the schedule specified in the respective arms.

Expansion Portion: PEGCISGEM

After the Investigators and the Sponsor considers the study treatment with PEGCISGEM during the Run-in portion safe and tolerable, new participants will be enrolled to receive 3.0 mcg/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. Treatment will continue until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity.

Group Type: EXPERIMENTAL

PEGPH20

Intervention Type: DRUG

PEGPH20 will be administered as per the schedule specified in the respective arms.

CIS

Intervention Type: DRUG

CIS will be administered as per the schedule specified in the respective arms.

GEM

Intervention Type: DRUG

GEM will be administered as per the schedule specified in the respective arms.

Expansion Portion: PEGCISGEMATEZO Twice Weekly

After the Investigators and the Sponsor considers the study treatment with PEGCISGEM during the Run-in portion safe and tolerable, new participants will be enrolled to receive 3.0 mcg/kg PEGPH20 on Days 1, 8, and 15 in combination with 1200 mg 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. Treatment will continue until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity.

Group Type: EXPERIMENTAL

PEGPH20

Intervention Type: DRUG

PEGPH20 will be administered as per the schedule specified in the respective arms.

CIS

Intervention Type: DRUG

CIS will be administered as per the schedule specified in the respective arms.

GEM

Intervention Type: DRUG

GEM will be administered as per the schedule specified in the respective arms.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered as per the schedule specified in the respective arms.

Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly

After the implementation of Protocol Amendment #3 and as communicated to the Investigators via a letter dated 22 March 2019, participants will receive 3.0 mcg/kg PEGPH20 on Days 1, 4, 8, 11, 15 and 18 in combination with 1200 mg ATEZO (administered 1 to 3 hours after PEGPH20 on Day 1 Cycle 1) plus 25 mg/m\^2 of CIS and 1000 mg/m\^2 GEM on Days 2 and 9 of Cycle 1 (cycle length = 21 days) by IV infusion. Participants will receive 3.0 mcg/kg PEGPH20 on Days 1, 8, and 15 in combination with 1200 mg 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 from Cycle 2 and beyond by IV infusion. Treatment will continue until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity.

Group Type: EXPERIMENTAL

PEGPH20

Intervention Type: DRUG

PEGPH20 will be administered as per the schedule specified in the respective arms.

CIS

Intervention Type: DRUG

CIS will be administered as per the schedule specified in the respective arms.

GEM

Intervention Type: DRUG

GEM will be administered as per the schedule specified in the respective arms.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered as per the schedule specified in the respective arms.

Expansion Portion: CISGEM

After the Investigators and the Sponsor considers the study treatment with PEGCISGEM during the run-in portion safe and tolerable, new participants will be enrolled to 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. Treatment will continue until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity.

Group Type: ACTIVE_COMPARATOR

CIS

Intervention Type: DRUG

CIS will be administered as per the schedule specified in the respective arms.

GEM

Intervention Type: DRUG

GEM will be administered as per the schedule specified in the respective arms.

Interventions

PEGPH20

PEGPH20 will be administered as per the schedule specified in the respective arms.

Intervention Type: DRUG

CIS

CIS will be administered as per the schedule specified in the respective arms.

Intervention Type: DRUG

GEM

GEM will be administered as per the schedule specified in the respective arms.

Intervention Type: DRUG

Atezolizumab

Atezolizumab will be administered as per the schedule specified in the respective arms.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Halozyme Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

VP, Medical, Regulatory and Drug Safety

Role: STUDY_DIRECTOR

Halozyme Therapeutics

Locations

Mayo Clinic of Arizona

Phoenix, Arizona, United States

University of Arizona

Tucson, Arizona, United States

City of Hope

Duarte, California, United States

Scripps

La Jolla, California, United States

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

University of California Irvine Division of Hematology-Oncology, Department of Medicine UC Irvine Health

Orange, California, United States

UC Davis

Sacramento, California, United States

UCLA - David Geffen School of Medicine

Santa Monica, California, United States

The Oncology Institute of Hope and Innovation

Whittier, California, United States

Yale Cancer Center

New Haven, Connecticut, United States

Lombardi Cancer Center, Georgetown University

Washington D.C., District of Columbia, United States

Johns Hopkins

Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mount Sinai

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Duke Cancer Institute

Durham, North Carolina, United States

Gabrail Cancer Center

Canton, Ohio, United States

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

MD Anderson Cancer Center

Houston, Texas, United States

UT Health Cancer Center

San Antonio, Texas, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Virginia Mason

Seattle, Washington, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Froedtert Hospital And Medical College

Milwaukee, Wisconsin, United States

Samsung Medical Center

Seoul, Gangnam-gu, South Korea

Korea University Guro Hospital

Seoul, Guro-gu, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Seoul National University Hospital

Seoul, Jongno-gu, South Korea

The Catholic University of Korea Seoul St. Mary's Hospital

Seoul, Seocho-gu, South Korea

Severance Hospital, Yonsei University Health System

Seoul, Seodaemun-Gu, South Korea

Asan Medical Center

Seoul, Songpa-gu, South Korea

Prince of Songkla University

Hat Yai, Changwat Songkhla, Thailand

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, Muang, Thailand

King Chulalongkorn Memorial Hospital

Bangkok, Patumwan, Thailand

Countries

United States; South Korea; Thailand

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

Halo-110-101

Identifier Type: -

Identifier Source: org_study_id