A Phase 1 interventional study of PEGPH20 and CIS in Cholangiocarcinoma Non-resectable, Cholangiocarcinoma, Intrahepatic and Cholangiocarcinoma, Extrahepatic, sponsored by Halozyme Therapeutics. Terminated at 36 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-02-07.
Sponsored by Halozyme Therapeutics · Phase 1, Interventional, and Treatment
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).
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.
824 studies on the registry are indexed under Cholangiocarcinoma; 287 are open to participants now.
This study's enrollment of 85 is above the median of 50 across 623 interventional studies indexed under Cholangiocarcinoma.
Browse Cholangiocarcinoma studies →Halozyme Therapeutics is the lead sponsor of 33 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
For both portions of the study, participants must satisfy all of the following inclusion criteria to be enrolled in the study:
Exclusion Criteria:
Participants are ineligible for enrollment if they meet any of the following exclusion criteria:
History of:
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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
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
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
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
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
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.
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'.
Time frame: 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'.
Time frame: 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'.
Time frame: 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'.
Time frame: 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.
Time frame: 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)
Run-in Portion: ORR Based on RECIST v1.1: Percentage of Participants With Objective Response
ORR was defined as percentage of participants who achieved either a CR or 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 \<10 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.
Time frame: 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
DOR was considered the time from date of the first CR or PR until the date of first documentation of disease progression or date of death based on RECIST v1.1 for target lesions assessed by MRI/CT scans, as determined by independent radiologic review. CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
Time frame: 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
PFS was based on RECIST v1.1 for target lesions assessed by MRI/CT scans, as determined by independent radiologic review and was defined as the time from randomization to radiological disease progression or death. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on or prior to the current assessment (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of greater than or equal to (≥) 5 mm.
Time frame: 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)
DCR was defined as the percentage of participants with CR, PR, or SD based on RECIST v1.1 for target lesions assessed by MRI/CT scans, as determined by independent radiologic review. CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.
Time frame: 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)
Overall survival was defined as the time from randomization until death from any cause.
Time frame: From randomization until death from any cause (maximum exposure: 421 days)
Expansion Portion: OS by PD-L1 Expression Levels
Overall survival was defined as the time from randomization until death from any cause.
Time frame: From randomization until death from any cause (maximum exposure: 421 days)
Expansion Portion: Number of Participants With 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. 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'.
Time frame: From first exposure to study drug through the end of treatment visit (maximum exposure: 421 days)
Expansion Portion: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters (Hematology and Blood Chemistry)
Laboratory parameters evaluation included hematology (hemoglobin, hematocrit, red blood cell count, WBC count, neutrophils \[ANC\], lymphocytes, monocytes, eosinophils, basophils, granulocytes, mean corpuscular hemoglobin, mean corpuscular volume, and platelet count) and blood chemistry (glucose, BUN, albumin, total bilirubin, alkaline phosphatase, AST, 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'.
Time frame: From first exposure to study drug through the end of treatment visit (maximum exposure: 421 days)
Expansion Portion: Number of Participants With Clinically Significant Abnormalities in 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'.
Time frame: From first exposure to study drug through the end of treatment visit (maximum exposure: 421 days)
Expansion Period: 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'.
Time frame: From first exposure to study drug through 30 days after the end of treatment visit (maximum exposure: 421 days)
Run-in and Expansion Portion : Maximum Observed Plasma Concentration (Cmax) of PEGPH20, ATEZO, GEM, and CIS
Plasma pharmacokinetic (PK) data were planned to be analyzed using a noncompartmental analysis approach.
Time frame: PEGPH20 and ATEZO: Cycle 1: multiple timepoints on Days 1, 2, 8, 9, 15; ATEZO: Day 1 of subsequent cycles and end of treatment (EOT) (maximum exposure: 508 days for run-in and 421 days for expansion); CIS and GEM: Cycle 1: multiple timepoints on Days 2,9
Run-in and Expansion Portion : Minimum Observed Plasma Concentration (Cmin) of PEGPH20 and ATEZO
PK data were planned to be analyzed using a noncompartmental analysis approach.
Time frame: PEGPH20 and ATEZO: Treatment Cycle 1: multiple timepoints on Days 1, 2, 8, 9, and 15; ATEZO: Day 1 of subsequent cycles and EOT visit (7 days after last 21-day cycle) (maximum exposure: 508 days for run-in portion and 421 days for expansion portion)
Run-in and Expansion Portion : Elimination Rate Constant (Kel) of PEGPH20
PK data were planned to be analyzed using a noncompartmental analysis approach.
Time frame: Cycle 1: multiple timepoints on Days 1, 2, 8, 9, and 15
Run-in and Expansion Portion : Terminal Elimination Plasma Half-life (t1/2) of PEGPH20, ATEZO, GEM, and CIS
PK data were planned to be analyzed using a noncompartmental analysis approach.
Time frame: PEGPH20 and ATEZO: Cycle 1: multiple timepoints on Days 1, 2, 8, 9, 15; ATEZO: Day 1 of subsequent cycles and EOT visit (maximum exposure: 508 days for run-in and 421 days for expansion portion); CIS and GEM: Cycle 1: multiple timepoints on Days 2, 9
Run-in and Expansion Portion : Clearance (CL) of PEGPH20, ATEZO, GEM, and CIS
PK data were planned to be analyzed using a noncompartmental analysis approach.
Time frame: PEGPH20 and ATEZO: Cycle 1: multiple timepoints on Days 1, 2, 8, 9, 15; ATEZO: Day 1 of subsequent cycles and EOT visit (maximum exposure: 508 days for run-in and 421 days for expansion portion); CIS and GEM: Cycle 1: multiple timepoints on Days 2, 9
Run-in and Expansion Portion : Volume of Distribution (Vd) of PEGPH20, ATEZO, GEM, and CIS
PK data were planned to be analyzed using a noncompartmental analysis approach.
Time frame: PEGPH20 and ATEZO: Cycle 1: multiple timepoints on Days 1, 2, 8, 9, 15; ATEZO: Day 1 of subsequent cycles and EOT visit (maximum exposure: 508 days for run-in and 421 days for expansion portion); CIS and GEM: Cycle 1: multiple timepoints on Days 2, 9
Run-in and Expansion Portion: Area Under the Concentration Time Curve (AUC) of PEGPH20, ATEZO, GEM, and CIS
PK data were planned to be analyzed using a noncompartmental analysis approach.
Time frame: PEGPH20 and ATEZO: Cycle 1: multiple timepoints on Days 1, 2, 8, 9, 15; ATEZO: Day 1 of subsequent cycles and EOT visit (maximum exposure: 508 days for run-in and 421 days for expansion portion); CIS and GEM: Cycle 1: multiple timepoints on Days 2, 9
The study was conducted in 2 portions: Run-in portion and Expansion portion.
| Milestone | Run-in Portion: PEGCISGEM | Run-in Portion: PEGCISGEMATEZO | Expansion Portion: PEGCISGEM | Expansion Portion: PEGCISGEMATEZO Twice Weekly | Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly | Expansion Portion: CISGEM |
|---|---|---|---|---|---|---|
| Started | 9 | 9 | 0 | 0 | 0 | 0 |
| Received at least 1 dose of study drug | 9 | 9 | 0 | 0 | 0 | 0 |
| Completed | 1 | 2 | 0 | 0 | 0 | 0 |
| Not completed | 8 | 7 | 0 | 0 | 0 | 0 |
| Withdrew: Investigator or sponsor decision | 1 | 2 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Sponsor terminated study | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Death | 7 | 3 | 0 | 0 | 0 | 0 |
| Milestone | Run-in Portion: PEGCISGEM | Run-in Portion: PEGCISGEMATEZO | Expansion Portion: PEGCISGEM | Expansion Portion: PEGCISGEMATEZO Twice Weekly | Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly | Expansion Portion: CISGEM |
|---|---|---|---|---|---|---|
| Started | 0 | 0 | 24 | 22 | 11 | 10 |
| Received at least 1 dose of study drug | 0 | 0 | 24 | 22 | 11 | 10 |
| Completed | 0 | 0 | 3 | 0 | 1 | 0 |
| Not completed | 0 | 0 | 21 | 22 | 10 | 10 |
| Withdrew: Other than specified | 0 | 0 | 0 | 3 | 2 | 0 |
| Withdrew: Investigator or sponsor decision | 0 | 0 | 2 | 1 | 2 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 2 | 1 | 1 | 1 |
| Withdrew: Sponsor terminated study | 0 | 0 | 7 | 4 | 5 | 3 |
| Withdrew: Death | 0 | 0 | 10 | 13 | 0 | 6 |
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'.
| Participants | Run-in Portion: PEGCISGEM | Run-in Portion: PEGCISGEMATEZO |
|---|---|---|
| Run-in Portion: Number of Participants With Adverse Events (AEs) | 9 | 9 |
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'.
| Participants | Run-in Portion: PEGCISGEM | Run-in Portion: PEGCISGEMATEZO |
|---|---|---|
| Run-in Portion: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters (Hematology and Blood Chemistry) | 0 | 0 |
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'.
No measurements were reported for this outcome.
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'.
| Participants | Run-in Portion: PEGCISGEM | Run-in Portion: PEGCISGEMATEZO |
|---|---|---|
| Run-in Portion: Number of Participants With AEs Leading to Dose Reduction or Interruption of Any Study Medication | 6 | 7 |
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.
No measurements were reported for this outcome.
ORR was defined as percentage of participants who achieved either a CR or 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 \<10 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.
No measurements were reported for this outcome.
DOR was considered the time from date of the first CR or PR until the date of first documentation of disease progression or date of death based on RECIST v1.1 for target lesions assessed by MRI/CT scans, as determined by independent radiologic review. CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
No measurements were reported for this outcome.
PFS was based on RECIST v1.1 for target lesions assessed by MRI/CT scans, as determined by independent radiologic review and was defined as the time from randomization to radiological disease progression or death. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on or prior to the current assessment (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of greater than or equal to (≥) 5 mm.
No measurements were reported for this outcome.
DCR was defined as the percentage of participants with CR, PR, or SD based on RECIST v1.1 for target lesions assessed by MRI/CT scans, as determined by independent radiologic review. CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.
No measurements were reported for this outcome.
Overall survival was defined as the time from randomization until death from any cause.
No measurements were reported for this outcome.
Overall survival was defined as the time from randomization until death from any cause.
No measurements were reported for this outcome.
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'.
| Participants | Expansion Portion: PEGCISGEM | Expansion Portion: PEGCISGEMATEZO Twice Weekly | Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly | Expansion Portion: CISGEM |
|---|---|---|---|---|
| Expansion Portion: Number of Participants With AEs | 24 | 22 | 10 | 10 |
Laboratory parameters evaluation included hematology (hemoglobin, hematocrit, red blood cell count, WBC count, neutrophils \[ANC\], lymphocytes, monocytes, eosinophils, basophils, granulocytes, mean corpuscular hemoglobin, mean corpuscular volume, and platelet count) and blood chemistry (glucose, BUN, albumin, total bilirubin, alkaline phosphatase, AST, 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'.
| Participants | Expansion Portion: PEGCISGEM | Expansion Portion: PEGCISGEMATEZO Twice Weekly | Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly | Expansion Portion: CISGEM |
|---|---|---|---|---|
| Expansion Portion: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters (Hematology and Blood Chemistry) | 0 | 0 | 0 | 0 |
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'.
No measurements were reported for this outcome.
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'.
| Participants | Expansion Portion: PEGCISGEM | Expansion Portion: PEGCISGEMATEZO Twice Weekly | Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly | Expansion Portion: CISGEM |
|---|---|---|---|---|
| Expansion Period: Number of Participants With AEs Leading to Dose Reduction or Interruption of Any Study Medication | 16 | 21 | 4 | 7 |
Plasma pharmacokinetic (PK) data were planned to be analyzed using a noncompartmental analysis approach.
No measurements were reported for this outcome.
PK data were planned to be analyzed using a noncompartmental analysis approach.
No measurements were reported for this outcome.
PK data were planned to be analyzed using a noncompartmental analysis approach.
No measurements were reported for this outcome.
PK data were planned to be analyzed using a noncompartmental analysis approach.
No measurements were reported for this outcome.
PK data were planned to be analyzed using a noncompartmental analysis approach.
No measurements were reported for this outcome.
PK data were planned to be analyzed using a noncompartmental analysis approach.
No measurements were reported for this outcome.
PK data were planned to be analyzed using a noncompartmental analysis approach.
No measurements were reported for this outcome.
Collected over From first exposure to study drug through 30 days after end of treatment visit (maximum exposure: 508 days for run-in portion and 421 days for expansion portion). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Run-in Portion: PEGCISGEM | 7/9 (77.8%) | 6/9 (66.7%) | 9/9 (100%) |
| Run-in Portion: PEGCISGEMATEZO | 3/9 (33.3%) | 2/9 (22.2%) | 9/9 (100%) |
| Expansion Portion: PEGCISGEM | 10/24 (41.7%) | 11/24 (45.8%) | 24/24 (100%) |
| Expansion Portion: PEGCISGEMATEZO Twice Weekly | 13/22 (59.1%) | 16/22 (72.7%) | 22/22 (100%) |
| Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly | 0/11 (0%) | 7/11 (63.6%) | 10/11 (90.9%) |
| Expansion Portion: CISGEM | 6/10 (60%) | 4/10 (40%) | 10/10 (100%) |
| Event | Run-in Portion: PEGCISGEM | Run-in Portion: PEGCISGEMATEZO | Expansion Portion: PEGCISGEM | Expansion Portion: PEGCISGEMATEZO Twice Weekly | Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly | Expansion Portion: CISGEM |
|---|---|---|---|---|---|---|
| PyrexiaGeneral disorders | 0/9 | 0/9 | 2/24 | 5/22 | 2/11 | 1/10 |
| AnaemiaBlood and lymphatic system disorders | 0/9 | 2/9 | 0/24 | 1/22 | 0/11 | 0/10 |
| ThrombocytopeniaBlood and lymphatic system disorders | 1/9 | 2/9 | 0/24 | 1/22 | 0/11 | 0/10 |
| VomitingGastrointestinal disorders | 2/9 | 0/9 | 0/24 | 1/22 | 0/11 | 1/10 |
| CholangitisHepatobiliary disorders | 1/9 | 0/9 | 0/24 | 4/22 | 0/11 | 0/10 |
| Blood bilirubin increasedInvestigations | 0/9 | 0/9 | 0/24 | 0/22 | 2/11 | 0/10 |
| AstheniaGeneral disorders | 0/9 | 0/9 | 0/24 | 3/22 | 0/11 | 0/10 |
| Febrile neutropeniaBlood and lymphatic system disorders | 1/9 | 0/9 | 0/24 | 0/22 | 0/11 | 0/10 |
| LeukopeniaBlood and lymphatic system disorders | 0/9 | 1/9 | 0/24 | 0/22 | 0/11 | 0/10 |
| NeutropeniaBlood and lymphatic system disorders | 0/9 | 1/9 | 1/24 | 1/22 | 0/11 | 0/10 |
| Event | Run-in Portion: PEGCISGEM | Run-in Portion: PEGCISGEMATEZO | Expansion Portion: PEGCISGEM | Expansion Portion: PEGCISGEMATEZO Twice Weekly | Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly | Expansion Portion: CISGEM |
|---|---|---|---|---|---|---|
| NauseaGastrointestinal disorders | 5/9 | 4/9 | 18/24 | 11/22 | 3/11 | 9/10 |
| FatigueGeneral disorders | 5/9 | 8/9 | 15/24 | 13/22 | 2/11 | 6/10 |
| AnaemiaBlood and lymphatic system disorders | 4/9 | 6/9 | 12/24 | 15/22 | 3/11 | 8/10 |
| Oedema peripheralGeneral disorders | 3/9 | 5/9 | 10/24 | 10/22 | 3/11 | 3/10 |
| ConstipationGastrointestinal disorders | 4/9 | 4/9 | 10/24 | 8/22 | 3/11 | 5/10 |
| VomitingGastrointestinal disorders | 3/9 | 3/9 | 12/24 | 7/22 | 1/11 | 5/10 |
| PyrexiaGeneral disorders | 1/9 | 1/9 | 6/24 | 11/22 | 3/11 | 5/10 |
| Platelet count decreasedInvestigations | 1/9 | 3/9 | 5/24 | 8/22 | 2/11 | 5/10 |
| Muscle spasmsMusculoskeletal and connective tissue disorders | 3/9 | 2/9 | 11/24 | 8/22 | 2/11 | 2/10 |
| ThrombocytopeniaBlood and lymphatic system disorders | 4/9 | 2/9 | 2/24 | 5/22 | 0/11 | 1/10 |
Enrolled population included all participants enrolled in the Run-in portion and the Expansion portion of the study.
| Age, Categorical(Participants) | Run-in Portion: PEGCISGEM | Run-in Portion: PEGCISGEMATEZO | Expansion Portion: PEGCISGEM | Expansion Portion: PEGCISGEMATEZO Twice Weekly | Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly | Expansion Portion: CISGEM | Total |
|---|---|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 7 | 3 | 15 | 10 | 4 | 6 | 45 |
| >=65 years | 2 | 6 | 9 | 12 | 7 | 4 | 40 |
| Sex: Female, Male(Participants) | Run-in Portion: PEGCISGEM | Run-in Portion: PEGCISGEMATEZO | Expansion Portion: PEGCISGEM | Expansion Portion: PEGCISGEMATEZO Twice Weekly | Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly | Expansion Portion: CISGEM | Total |
|---|---|---|---|---|---|---|---|
| Female | 6 | 2 | 13 | 8 | 6 | 8 | 43 |
| Male | 3 | 7 | 11 | 14 | 5 | 2 | 42 |
| Ethnicity (NIH/OMB)(Participants) | Run-in Portion: PEGCISGEM | Run-in Portion: PEGCISGEMATEZO | Expansion Portion: PEGCISGEM | Expansion Portion: PEGCISGEMATEZO Twice Weekly | Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly | Expansion Portion: CISGEM | Total |
|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 1 | 0 | 1 | 2 |
| Not Hispanic or Latino | 9 | 8 | 24 | 21 | 11 | 8 | 81 |
| Unknown or Not Reported | 0 | 1 | 0 | 0 | 0 | 1 | 2 |
| Race (NIH/OMB)(Participants) | Run-in Portion: PEGCISGEM | Run-in Portion: PEGCISGEMATEZO | Expansion Portion: PEGCISGEM | Expansion Portion: PEGCISGEMATEZO Twice Weekly | Expansion Portion: PEGCISGEMATEZO Once Weekly/Twice Weekly | Expansion Portion: CISGEM | Total |
|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 4 | 4 | 9 | 7 | 3 | 4 | 31 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| White | 5 | 4 | 14 | 14 | 7 | 6 | 50 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 1 | 1 | 1 | 0 | 3 |
Plan to share: No
This study is terminated, as verified in Jan 2020. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: PEGPH20