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
- Conditions
- Carcinoma, Hepatocellular
- Interventions
- Registration Number
- NCT01911273
- Lead Sponsor
- Pfizer
- 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
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 3
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PF 03446962 plus best supportive care (BSC) PF-03446962 - Placebo plus best supportive care (BSC) Placebo Placebo, IV, every 2 weeks, until disease progression, patient refusal or unacceptable toxicity, whichever occurs first PF 03446962 plus best supportive care (BSC) Best Supportive Care - Placebo plus best supportive care (BSC) Best Supportive Care Placebo, IV, every 2 weeks, until disease progression, patient refusal or unacceptable toxicity, whichever occurs first
- Primary Outcome Measures
Name Time Method Overall Survival (OS) From first randomization to date of death from any cause, whichever came first, assessed up to 24 months after last participant randomization 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
Name Time Method Number of Participants With Human Anti-Human Antibodies (HAHA) Cycle 1, 2, 4, 6, 8 Day 1 at 0 hour (pre-dose) Time to Tumor Progression (TTP) Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization. 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) Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization. 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 Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization. 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) 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 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 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 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) Screening, Cycle 1 Day1,8; Cycle >=2 Day1; End of treatment, survival follow-up up to 24 months after last participant randomization. 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) 1 hour (after start of infusion) on Day1 of Cycles 1, 2, 4, 6, and 8 Trough Serum Concentration of PF-03446962 (Ctrough) 0 hour (predose) on Day 1 of Cycles 1, 2, 4, 6, and 8 Presence of Sensitivity Signature Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal. Tumor molecular characteristics including but not limited to transcriptomic (RNA) signatures of sensitivity
Ratio to Baseline of Serum Circulating Protein Concentration Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal. 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 Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.
Trial Locations
- Locations (4)
Kinki University Hospital, Department of Gastroenterology and Hepatology
🇯🇵Osaka-Sayama, Osaka, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan