Back to resultsA Study To Evaluate The Efficacy And Safety of The Investigational Drug PF-03446962 (A Monoclonal Antibody With Antiangiogenic Features) In Combination With Best Supportive Care Versus Placebo Plus Best Supportive Care In Patients Affected By Recurrent Liver Cancer
Primary Purpose
Carcinoma, Hepatocellular
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PF-03446962
Best Supportive Care
Placebo
Best Supportive Care
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Hepatocellular focused on measuring Hepatocellular carcinoma, monoclonal antibody, ALK-1, best supportive care
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of locally advanced or metastatic liver cancer obtained by histology/cytology or by imaging
- Documented progression on or after treatment with sorafenib, confirmed by the Investigator upon review of appropriate imaging documentation
- Child Pugh Class A disease
- ECOG [Eastern Cooperative Oncology Group] Performance Status (PS) 0 or 1
- Mandatory tumor biopsy at study entry (pre-randomization, unless already collected after sorafenib progression but within 3 months of enrollment and no systemic anticancer therapies received)
Exclusion Criteria:
- Prior systemic treatment for advanced liver cancer other than sorafenib-including therapy
- Prior local therapy within 2 weeks of starting the study treatment
- Presence of main portal vein invasion by liver cancer
Sites / Locations
- Fox Chase Cancer Center
- National Cancer Center Hospital East
- Kinki University Hospital, Department of Gastroenterology and Hepatology
- National Cancer Center Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
PF 03446962 plus best supportive care (BSC)
Placebo plus best supportive care (BSC)
Arm Description
Placebo, IV, every 2 weeks, until disease progression, patient refusal or unacceptable toxicity, whichever occurs first
Outcomes
Primary Outcome Measures
Overall Survival (OS)
OS was the duration from date of randomization to date of death due to any cause. For participants who are alive, overall survival was censored at the last contact. Death was determined from adverse event (AE) data where outcome was death or from follow-up contact data where the participant current status was death.
Secondary Outcome Measures
Time to Tumor Progression (TTP)
TTP was defined as the time from first randomization to date of first documentation of objective tumor progression. If tumor progression data included more than (>) 1 date, the first date was to be used. TTP (in months) was calculated as first event date or last known progression-free date minus the first randomization date plus 1 divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1).
Progression-Free Survival (PFS)
PFS was defined as the time from randomization to first documentation of objective tumor progression or to death due to any cause, whichever occured first. If tumor progression data included >1 date, the first date was to be used. PFS (in months) was calculated as first event date minus first randomization date plus 1 divided by 30.4.
Objective Response Rate (ORR) - Percentage of Participants With Objective Response
ORR was defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.1, relative to all randomized participants. CR were those that persisted on repeat imaging study more than or equal to (>=) 4 weeks after initial documentation of response. PR was defined as >=30% decrease in the sum of diameters of target lesions and non CR/non PD to non-target lesions. Participants who did not have on study radiographic tumor re-evaluation or who died, progressed or dropped out for any reason prior to reaching a CR or PR were to be counted as non-responders in the assessment of ORR. A participant who initially met the criteria for a PR and then subsequently became a confirmed CR, was to be assigned a best response of CR.
Duration of Response (DR)
DR was defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. If tumor progression data included >1 date, the first date was to be used. DR (in months) was calculated as the end date for DR minus date of first CR or PR that was subsequently confirmed plus 1 divided by 30.4. CR was defined as disappearance of all target lesions and non-target, if any. PR was defined as >=30% decrease in the sum of diameters of target lesions and non CR/non PD to non-target lesions.
Percentage of Participants With Disease Control Rate (DCR) at 16 Weeks
DCR was defined as the proportion of participants with confirmed CR or confirmed PR or a best response of stable disease (SD) >=16 weeks according to RECIST, relative to all randomized participants. CR was defined as disappearance of all target lesions. PR was defined as >=30% decrease in the sum of diameters of target lesions and non CR/non PD to non-target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study.
Change From Baseline in Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire (FACT-Hep)
Patient reported outcomes (PROs) were assessed using the FACT-Hep. The FACT-Hep included the FACT-general (FACT-G) and a hepatobiliary module, it consisted of the 27-item FACT-G, which assessed generic health-related quality of life (HRQoL) concerns, and the 18-item hepatobiliary subscale (HS), which assessed disease-specific issues. The questionnaire used a 5 point Likert scale from '0' "not at all" to '4' "very much" regarding how much each item was present in the last 7 days; lower score indicated severer symptom. Eight of the items (lack of energy, pain, weight loss, back pain, fatigue, stomach pain/discomfort, nausea, and jaundice) made up the Fact Hepatobiliary Symptom Index (FHSI 8) were considered to be symptoms specific to hepatobiliary cancer.
Maximum Serum Concentration (Cmax)
Trough Serum Concentration of PF-03446962 (Ctrough)
Number of Participants With Human Anti-Human Antibodies (HAHA)
Presence of Sensitivity Signature
Tumor molecular characteristics including but not limited to transcriptomic (RNA) signatures of sensitivity
Ratio to Baseline of Serum Circulating Protein Concentration
Protein involved TGFB1, VEGF-A, VEGF-C, PIGF, Endoglin, BMP-9, VEGFR1, VEGFR2, VEGFr3, Ang-2, VEGF-D, CD54, CD106, and CCL2. Tumor molecular characteristics including but not limited to transcriptomic (ribonucleic acid) signatures of efficacy.
Observed Serum Concentration of Circulating Protein
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01911273
Brief Title
A Study To Evaluate The Efficacy And Safety of The Investigational Drug PF-03446962 (A Monoclonal Antibody With Antiangiogenic Features) In Combination With Best Supportive Care Versus Placebo Plus Best Supportive Care In Patients Affected By Recurrent Liver Cancer
Official Title
A Phase 2, Randomized, Double Blind Study To Evaluate The Efficacy, Safety, Pharmacodynamics And Pharmacokinetics Of The Anti-alk-1 Monoclonal Antibody Pf-03446962 In Combination With Best Supportive Care Vs. Placebo Plus Best Supportive Care In Adult Patients With Advanced Hepatocellular Carcinoma Following Failure Of Sorafenib
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Terminated
Why Stopped
See termination reason in detailed description.
Study Start Date
October 2013 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary purpose of the study is to explore whether treatment with PF-03446962 and best supportive care is better than placebo plus best supportive care in prolonging survival of patients affected by recurrent liver cancer. In addition, the study will explore if adding PF-03446962 to best supportive care is safe, how PF-03446962 is metabolized, if there are patients' characteristics (biomarkers) that may predict response to PF-03446962, and if PF-03446962 has any effect on the patients' quality of life.
Detailed Description
This study was terminated on June 24th, 2014 due to change in strategy of PF-03446962 clinical development. There were no safety or efficacy concerns regarding the study behind the decision to terminate the trial. The study was on temporary halt since March 10th and there are currently no patients on treatment or in the process of being randomized
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Hepatocellular
Keywords
Hepatocellular carcinoma, monoclonal antibody, ALK-1, best supportive care
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PF 03446962 plus best supportive care (BSC)
Arm Type
Experimental
Arm Title
Placebo plus best supportive care (BSC)
Arm Type
Placebo Comparator
Arm Description
Placebo, IV, every 2 weeks, until disease progression, patient refusal or unacceptable toxicity, whichever occurs first
Intervention Type
Drug
Intervention Name(s)
PF-03446962
Intervention Description
PF 03446962 7 mg/kg, IV, every 2 weeks, until disease progression, patient refusal or unacceptable toxicity, whichever occurs first
Intervention Type
Other
Intervention Name(s)
Best Supportive Care
Intervention Description
BSC may include medications and supportive measures deemed necessary to palliate disease related symptoms and improve quality of life
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo will consist of Saline (0.9% w/v Sodium Chloride Injection, USP or NS)
Intervention Type
Other
Intervention Name(s)
Best Supportive Care
Intervention Description
BSC may include medications and supportive measures deemed necessary to palliate disease related symptoms and improve quality of life.
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
OS was the duration from date of randomization to date of death due to any cause. For participants who are alive, overall survival was censored at the last contact. Death was determined from adverse event (AE) data where outcome was death or from follow-up contact data where the participant current status was death.
Time Frame
From first randomization to date of death from any cause, whichever came first, assessed up to 24 months after last participant randomization
Secondary Outcome Measure Information:
Title
Time to Tumor Progression (TTP)
Description
TTP was defined as the time from first randomization to date of first documentation of objective tumor progression. If tumor progression data included more than (>) 1 date, the first date was to be used. TTP (in months) was calculated as first event date or last known progression-free date minus the first randomization date plus 1 divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1).
Time Frame
Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization.
Title
Progression-Free Survival (PFS)
Description
PFS was defined as the time from randomization to first documentation of objective tumor progression or to death due to any cause, whichever occured first. If tumor progression data included >1 date, the first date was to be used. PFS (in months) was calculated as first event date minus first randomization date plus 1 divided by 30.4.
Time Frame
Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization.
Title
Objective Response Rate (ORR) - Percentage of Participants With Objective Response
Description
ORR was defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.1, relative to all randomized participants. CR were those that persisted on repeat imaging study more than or equal to (>=) 4 weeks after initial documentation of response. PR was defined as >=30% decrease in the sum of diameters of target lesions and non CR/non PD to non-target lesions. Participants who did not have on study radiographic tumor re-evaluation or who died, progressed or dropped out for any reason prior to reaching a CR or PR were to be counted as non-responders in the assessment of ORR. A participant who initially met the criteria for a PR and then subsequently became a confirmed CR, was to be assigned a best response of CR.
Time Frame
Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization.
Title
Duration of Response (DR)
Description
DR was defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. If tumor progression data included >1 date, the first date was to be used. DR (in months) was calculated as the end date for DR minus date of first CR or PR that was subsequently confirmed plus 1 divided by 30.4. CR was defined as disappearance of all target lesions and non-target, if any. PR was defined as >=30% decrease in the sum of diameters of target lesions and non CR/non PD to non-target lesions.
Time Frame
From first randomization to date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months after last participant randomization
Title
Percentage of Participants With Disease Control Rate (DCR) at 16 Weeks
Description
DCR was defined as the proportion of participants with confirmed CR or confirmed PR or a best response of stable disease (SD) >=16 weeks according to RECIST, relative to all randomized participants. CR was defined as disappearance of all target lesions. PR was defined as >=30% decrease in the sum of diameters of target lesions and non CR/non PD to non-target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study.
Time Frame
From first randomization to date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months after last participant randomization
Title
Change From Baseline in Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire (FACT-Hep)
Description
Patient reported outcomes (PROs) were assessed using the FACT-Hep. The FACT-Hep included the FACT-general (FACT-G) and a hepatobiliary module, it consisted of the 27-item FACT-G, which assessed generic health-related quality of life (HRQoL) concerns, and the 18-item hepatobiliary subscale (HS), which assessed disease-specific issues. The questionnaire used a 5 point Likert scale from '0' "not at all" to '4' "very much" regarding how much each item was present in the last 7 days; lower score indicated severer symptom. Eight of the items (lack of energy, pain, weight loss, back pain, fatigue, stomach pain/discomfort, nausea, and jaundice) made up the Fact Hepatobiliary Symptom Index (FHSI 8) were considered to be symptoms specific to hepatobiliary cancer.
Time Frame
Screening, Cycle 1 Day1,8; Cycle >=2 Day1; End of treatment, survival follow-up up to 24 months after last participant randomization.
Title
Maximum Serum Concentration (Cmax)
Time Frame
1 hour (after start of infusion) on Day1 of Cycles 1, 2, 4, 6, and 8
Title
Trough Serum Concentration of PF-03446962 (Ctrough)
Time Frame
0 hour (predose) on Day 1 of Cycles 1, 2, 4, 6, and 8
Title
Number of Participants With Human Anti-Human Antibodies (HAHA)
Time Frame
Cycle 1, 2, 4, 6, 8 Day 1 at 0 hour (pre-dose)
Title
Presence of Sensitivity Signature
Description
Tumor molecular characteristics including but not limited to transcriptomic (RNA) signatures of sensitivity
Time Frame
Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.
Title
Ratio to Baseline of Serum Circulating Protein Concentration
Description
Protein involved TGFB1, VEGF-A, VEGF-C, PIGF, Endoglin, BMP-9, VEGFR1, VEGFR2, VEGFr3, Ang-2, VEGF-D, CD54, CD106, and CCL2. Tumor molecular characteristics including but not limited to transcriptomic (ribonucleic acid) signatures of efficacy.
Time Frame
Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.
Title
Observed Serum Concentration of Circulating Protein
Time Frame
Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of locally advanced or metastatic liver cancer obtained by histology/cytology or by imaging
Documented progression on or after treatment with sorafenib, confirmed by the Investigator upon review of appropriate imaging documentation
Child Pugh Class A disease
ECOG [Eastern Cooperative Oncology Group] Performance Status (PS) 0 or 1
Mandatory tumor biopsy at study entry (pre-randomization, unless already collected after sorafenib progression but within 3 months of enrollment and no systemic anticancer therapies received)
Exclusion Criteria:
Prior systemic treatment for advanced liver cancer other than sorafenib-including therapy
Prior local therapy within 2 weeks of starting the study treatment
Presence of main portal vein invasion by liver cancer
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
National Cancer Center Hospital East
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Facility Name
Kinki University Hospital, Department of Gastroenterology and Hepatology
City
Osaka-Sayama
State/Province
Osaka
ZIP/Postal Code
589-8511
Country
Japan
Facility Name
National Cancer Center Hospital
City
Chuo-ku
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
12. IPD Sharing Statement
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A8471005
Description
To obtain contact information for a study center near you, click here.
Learn more about this trial
A Study To Evaluate The Efficacy And Safety of The Investigational Drug PF-03446962 (A Monoclonal Antibody With Antiangiogenic Features) In Combination With Best Supportive Care Versus Placebo Plus Best Supportive Care In Patients Affected By Recurrent Liver Cancer
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