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

NCT03267940 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: Halo-110-101
• Study Type: interventional
• Target: 85
• Locations: 3 countries
• Sites: 36

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).

Conditions

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

Keywords

Extrahepatic Cholangiocarcinoma; Intrahepatic Cholangiocarcinoma; Gallbladder Adenocarcinoma; PEGylated Recombinant Human Hyaluronidase; PEGylated Recombinant Human Hyaluronidase with atezolizumab

Outcome Measures

Primary Outcomes (5)

• Run-in Portion: Number of Participants With Adverse Events (AEs)

  An AE is any unfavorable or unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product (for example, study drug), whether or not considered related to the pharmaceutical product. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

  From first exposure to study drug through 30 days after the end of treatment visit (maximum exposure: 508 days)

• Run-in Portion: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters (Hematology and Blood Chemistry)

  Laboratory parameters evaluation included hematology (hemoglobin, hematocrit, red blood cell count, white blood cell \[WBC\] count, neutrophils \[ANC\], lymphocytes, monocytes, eosinophils, basophils, granulocytes, mean corpuscular hemoglobin, mean corpuscular volume, and platelet count) and blood chemistry (glucose, blood urea nitrogen \[BUN\], albumin, total bilirubin, alkaline phosphatase, aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], electrolytes \[including sodium, potassium, calcium, magnesium, chloride, and bicarbonate\], and creatinine) evaluation. Clinical significance was defined as per Investigator's discretion. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

  From first exposure to study drug through the end of treatment visit (maximum exposure: 508 days)

• Run-in Portion: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) and Vital Signs

  Clinical significance of ECGs was defined as per Investigator's discretion. Assessment of vital signs was to include the measurement of blood pressure (systolic and diastolic), pulse, respiratory rate, and body temperature. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

  From first exposure to study drug through the end of treatment visit (maximum exposure: 508 days)

• Run-in Portion: Number of Participants With AEs Leading to Dose Reduction or Interruption of Any Study Medication

  Number of participants with AEs leading to dose reduction or interruption of any study medication (PEGPH20, CIS, GEM, or ATEZO) was reported. An AE is any unfavorable or unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product (for example, study drug), whether or not considered related to the pharmaceutical product. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

  From first exposure to study drug through the end of treatment visit (maximum exposure: 508 days)

• Expansion Portion: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1: Percentage of Participants With Objective Response

  ORR was defined as percentage of participants who achieved either a complete response (CR) or partial response (PR). CR was defined as disappearance of all target and non-target lesions; Any pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  From date of randomization until the date of first documented progression of disease or date of death from any cause, whichever came first (maximum exposure: 421 days)

Secondary Outcomes (17)

• Run-in Portion: ORR Based on RECIST v1.1: Percentage of Participants With Objective Response

  From date of randomization until the date of first documented progression of disease or date of death from any cause, whichever came first (maximum exposure: 508 days)

• Expansion Portion: Duration of Response (DOR) Based on RECIST v1.1

  From date of the first CR or PR until the date of first documentation of disease progression or date of death, whichever came first (maximum exposure: 421 days)

• Expansion Portion: Progression-Free Survival (PFS) Based on RECIST v1.1

  From date of randomization until date of progressive disease or death from any cause, whichever came first (maximum exposure: 421 days)

• Expansion Portion: Disease Control Rate (DCR) Based on RECIST v1.1: Percentage of Participants With CR, PR or Stable Disease (SD)

  From date of randomization until date of progressive disease or death from any cause, whichever came first (maximum exposure: 421 days)

• Expansion Portion: Overall Survival (OS)

  From randomization until death from any cause (maximum exposure: 421 days)

Study Arms (6)

Run-in Portion: PEGCISGEM

EXPERIMENTAL

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.

Drug: PEGPH20; Drug: CIS; Drug: GEM

Run-in Portion: PEGCISGEMATEZO

EXPERIMENTAL

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.

Drug: PEGPH20; Drug: CIS; Drug: GEM; Drug: Atezolizumab

Expansion Portion: PEGCISGEM

EXPERIMENTAL

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.

Drug: PEGPH20; Drug: CIS; Drug: GEM

Expansion Portion: PEGCISGEMATEZO Twice Weekly

EXPERIMENTAL

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.

Drug: PEGPH20; Drug: CIS; Drug: GEM; Drug: Atezolizumab

Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly

EXPERIMENTAL

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.

Drug: PEGPH20; Drug: CIS; Drug: GEM; Drug: Atezolizumab

Expansion Portion: CISGEM

ACTIVE COMPARATOR

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.

Drug: CIS; Drug: GEM

Interventions

PEGPH20 DRUG

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

Expansion Portion: PEGCISGEM; Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly; Expansion Portion: PEGCISGEMATEZO Twice Weekly; Run-in Portion: PEGCISGEM; Run-in Portion: PEGCISGEMATEZO

CIS DRUG

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

Expansion Portion: CISGEM; Expansion Portion: PEGCISGEM; Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly; Expansion Portion: PEGCISGEMATEZO Twice Weekly; Run-in Portion: PEGCISGEM; Run-in Portion: PEGCISGEMATEZO

GEM DRUG

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

Expansion Portion: CISGEM; Expansion Portion: PEGCISGEM; Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly; Expansion Portion: PEGCISGEMATEZO Twice Weekly; Run-in Portion: PEGCISGEM; Run-in Portion: PEGCISGEMATEZO

Atezolizumab DRUG

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

Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly; Expansion Portion: PEGCISGEMATEZO Twice Weekly; Run-in Portion: PEGCISGEMATEZO

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.
• 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.
• Or known cases of drug-induced hepatobiliary toxicities.
• Active or history of autoimmune diseases

Sponsors & Collaborators

• Halozyme Therapeutics: lead

Study Sites (36)

Mayo Clinic of Arizona

Phoenix, Arizona, 85054, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Scripps

La Jolla, California, 92037, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

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

Orange, California, 92868, United States

Location

UC Davis

Sacramento, California, 95817, United States

Location

UCLA - David Geffen School of Medicine

Santa Monica, California, 90404, United States

Location

The Oncology Institute of Hope and Innovation

Whittier, California, 90603, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06511, United States

Location

Lombardi Cancer Center, Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

UT Health Cancer Center

San Antonio, Texas, 78229, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Virginia Mason

Seattle, Washington, 98101, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Froedtert Hospital And Medical College

Milwaukee, Wisconsin, 53226, United States

Location

Samsung Medical Center

Seoul, Gangnam-gu, 06351, South Korea

Location

Korea University Guro Hospital

Seoul, Guro-gu, 08308, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, Jongno-gu, 03080, South Korea

Location

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

Seoul, Seocho-gu, 06591, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, Seodaemun-Gu, 03722, South Korea

Location

Asan Medical Center

Seoul, Songpa-gu, 05505, South Korea

Location

Prince of Songkla University

Hat Yai, Changwat Songkhla, 90110, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, Muang, 50200, Thailand

Location

King Chulalongkorn Memorial Hospital

Bangkok, Patumwan, 10330, Thailand

Location

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

PEGPH20; atezolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Limitations and Caveats

The study was terminated prematurely by the Sponsor due to stopping the clinical development of PEGPH20 in all indications based on negative pivotal data in metastatic pancreatic cancer.

Results Point of Contact

• Title: VP, Medical, Regulatory and Drug Safety
• Organization: Halozyme Therapeutics

medinfo@halozyme.com

858-794-8889

Study Officials

• VP, Medical, Regulatory and Drug Safety

  Halozyme Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2017
• First Posted: August 31, 2017
• Study Start: October 2, 2017
• Primary Completion: November 11, 2019
• Study Completion: November 11, 2019
• Last Updated: February 7, 2020
• Results First Posted: February 7, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

TH (3); US (26); KR (7)