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

October 6, 2015 updated by: Pfizer

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Chiba
      • Kashiwa, Chiba, Japan, 277-8577
        • National Cancer Center Hospital East
    • Osaka
      • Osaka-Sayama, Osaka, Japan, 589-8511
        • Kinki University Hospital, Department of Gastroenterology and Hepatology
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: PF 03446962 plus best supportive care (BSC)
Drug: PF-03446962
PF 03446962 7 mg/kg, IV, every 2 weeks, until disease progression, patient refusal or unacceptable toxicity, whichever occurs first
Other: Best Supportive Care
BSC may include medications and supportive measures deemed necessary to palliate disease related symptoms and improve quality of life
Other: Best Supportive Care
BSC may include medications and supportive measures deemed necessary to palliate disease related symptoms and improve quality of life.
Placebo Comparator: Placebo plus best supportive care (BSC)
Placebo, IV, every 2 weeks, until disease progression, patient refusal or unacceptable toxicity, whichever occurs first
Other: Best Supportive Care
BSC may include medications and supportive measures deemed necessary to palliate disease related symptoms and improve quality of life
Other: Best Supportive Care
BSC may include medications and supportive measures deemed necessary to palliate disease related symptoms and improve quality of life.
Other: Placebo
Placebo will consist of Saline (0.9% w/v Sodium Chloride Injection, USP or NS)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 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.
From first randomization to date of death from any cause, whichever came first, assessed up to 24 months after last participant randomization

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to Tumor Progression (TTP)
Time Frame: 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).
Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization.
Progression-Free Survival (PFS)
Time Frame: 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.
Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization.
Objective Response Rate (ORR) - Percentage of Participants With Objective Response
Time Frame: 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.
Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization.
Duration of Response (DR)
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
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.
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
Percentage of Participants With Disease Control Rate (DCR) at 16 Weeks
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
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.
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
Change From Baseline in Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire (FACT-Hep)
Time Frame: 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.
Screening, Cycle 1 Day1,8; Cycle >=2 Day1; End of treatment, survival follow-up up to 24 months after last participant randomization.
Maximum Serum Concentration (Cmax)
Time Frame: 1 hour (after start of infusion) on Day1 of Cycles 1, 2, 4, 6, and 8
1 hour (after start of infusion) on Day1 of Cycles 1, 2, 4, 6, and 8
Trough Serum Concentration of PF-03446962 (Ctrough)
Time Frame: 0 hour (predose) on Day 1 of Cycles 1, 2, 4, 6, and 8
0 hour (predose) on Day 1 of Cycles 1, 2, 4, 6, and 8
Number of Participants With Human Anti-Human Antibodies (HAHA)
Time Frame: Cycle 1, 2, 4, 6, 8 Day 1 at 0 hour (pre-dose)
Cycle 1, 2, 4, 6, 8 Day 1 at 0 hour (pre-dose)
Presence of Sensitivity Signature
Time Frame: 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
Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.
Ratio to Baseline of Serum Circulating Protein Concentration
Time Frame: 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.
Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.
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.
Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 26, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 26, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 30, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 28, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 6, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • A8471005
  • 2013-001426-26 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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