A Phase 1B, Randomized, Open-Label Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) in Combination With Cisplatin Plus Gemcitabine and PEGPH20 in Combination With Atezolizumab and Cisplatin Plus Gemcitabine Compared With Cisplatin Plus Gemcitabine in Subjects With Previously Untreated, Unresectable, Locally Advanced, or Metastatic Intrahepatic and Extrahepatic Cholangiocarcinoma and Gallbladder Adenocarcinoma

Status: Terminated
Location: See all (36) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1
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
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
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⁃ 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.

Locations
United States
Arizona
Mayo Clinic of Arizona
Phoenix
University of Arizona
Tucson
California
City of Hope
Duarte
Scripps
La Jolla
USC/Norris Comprehensive Cancer Center
Los Angeles
University of California Irvine Division of Hematology-Oncology, Department of Medicine UC Irvine Health
Orange
UC Davis
Sacramento
UCLA - David Geffen School of Medicine
Santa Monica
The Oncology Institute of Hope and Innovation
Whittier
Connecticut
Yale Cancer Center
New Haven
Washington, D.c.
Lombardi Cancer Center, Georgetown University
Washington
Massachusetts
Beth Israel Deaconess Medical Center
Boston
Maryland
Johns Hopkins
Baltimore
Missouri
Washington University School of Medicine
Saint Louis
North Carolina
Duke Cancer Institute
Durham
New York
Mount Sinai
New York
University of Rochester Medical Center
Rochester
Ohio
Gabrail Cancer Center
Canton
Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh
South Carolina
Medical University of South Carolina
Charleston
Texas
MD Anderson Cancer Center
Houston
UT Health Cancer Center
San Antonio
Utah
Huntsman Cancer Institute
Salt Lake City
Washington
Seattle Cancer Care Alliance
Seattle
Virginia Mason
Seattle
Wisconsin
Froedtert Hospital And Medical College
Milwaukee
Other Locations
Republic of Korea
Seoul National University Bundang Hospital
Seongnam-si
Asan Medical Center
Seoul
Korea University Guro Hospital
Seoul
Samsung Medical Center
Seoul
Seoul National University Hospital
Seoul
Severance Hospital, Yonsei University Health System
Seoul
The Catholic University of Korea Seoul St. Mary's Hospital
Seoul
Thailand
King Chulalongkorn Memorial Hospital
Bangkok
Maharaj Nakorn Chiang Mai Hospital
Chiang Mai
Prince of Songkla University
Hat Yai
Time Frame
Start Date: 2017-10-02
Completion Date: 2019-11-11
Participants
Target number of participants: 85
Treatments
Experimental: 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.
Experimental: 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.
Experimental: 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.
Experimental: 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.
Experimental: 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.
Active_comparator: 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.
Sponsors
Leads: Halozyme Therapeutics

This content was sourced from clinicaltrials.gov