Clinical trial NCT01911273: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Carcinoma, Hepatocellular
Keywords: Hepatocellular carcinoma
monoclonal antibody
ALK-1
best supportive care
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-07-30
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From first randomization to date of death from any cause, whichever came first, assessed up to 24 months after last participant randomization
Secondary outcomes:
measure: Time to Tumor Progression (TTP)
timeFrame: Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization.
measure: Progression-Free Survival (PFS)
timeFrame: Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization.
measure: Objective Response Rate (ORR) - Percentage of Participants With Objective Response
timeFrame: Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization.
measure: Duration of Response (DR)
timeFrame: 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
measure: Percentage of Participants With Disease Control Rate (DCR) at 16 Weeks
timeFrame: 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
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire (FACT-Hep)
timeFrame: Screening, Cycle 1 Day1,8; Cycle >=2 Day1; End of treatment, survival follow-up up to 24 months after last participant randomization.
measure: Maximum Serum Concentration (Cmax)
timeFrame: 1 hour (after start of infusion) on Day1 of Cycles 1, 2, 4, 6, and 8
measure: Trough Serum Concentration of PF-03446962 (Ctrough)
timeFrame: 0 hour (predose) on Day 1 of Cycles 1, 2, 4, 6, and 8
measure: Number of Participants With Human Anti-Human Antibodies (HAHA)
timeFrame: Cycle 1, 2, 4, 6, 8 Day 1 at 0 hour (pre-dose)
measure: Presence of Sensitivity Signature
timeFrame: Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.
measure: Ratio to Baseline of Serum Circulating Protein Concentration
timeFrame: Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.
measure: Observed Serum Concentration of Circulating Protein
timeFrame: Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Osaka-Sayama
country: Japan
facility: Kinki University Hospital, Department of Gastroenterology and Hepatology
state: Osaka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: