Carcinoma, HepatocellularPhase 2NCT01911273
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
A Phase 2 study testing PF-03446962 in people with Carcinoma, Hepatocellular, run by Pfizer at 4 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- PF-03446962
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Oct 2013to Jul 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Japan3 sites
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
Kinki University Hospital, Department of Gastroenterology and Hepatology
Ōsaka-sayama, Osaka, 589-8511
United States1 site
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
About this study
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
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.
Read the 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
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- PF-03446962, Best Supportive Care, Placebo
- Keywords
- Hepatocellular carcinoma, monoclonal antibody, ALK-1, best supportive care
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-03446962Drug
PF 03446962 7 mg/kg, IV, every 2 weeks, until disease progression, patient refusal or unacceptable toxicity, whichever occurs first
Best Supportive CareOther
BSC may include medications and supportive measures deemed necessary to palliate disease related symptoms and improve quality of life
PlaceboOther
Placebo will consist of Saline (0.9% w/v Sodium Chloride Injection, USP or NS)
Best Supportive CareOther
BSC may include medications and supportive measures deemed necessary to palliate disease related symptoms and improve quality of life.
| Study group | Role | What they receive |
|---|---|---|
| PF 03446962 plus best supportive care (BSC) | Experimental | Not described Receives: Drug: PF-03446962; Other: Best Supportive Care |
| Placebo plus best supportive care (BSC) | Placebo comparator | Placebo, IV, every 2 weeks, until disease progression, patient refusal or unacceptable toxicity, whichever occurs first Receives: Other: Placebo; Other: Best Supportive Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From first randomization to date of death from any cause, whichever came first, assessed up to 24 months after last participant randomization
Secondary outcomes (12)
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).
Measured: Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization.
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.
Measured: 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
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.
Measured: Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization.
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.
Measured: 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
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.
Measured: 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)
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.
Measured: 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)
Measured: 1 hour (after start of infusion) on Day1 of Cycles 1, 2, 4, 6, and 8
Trough Serum Concentration of PF-03446962 (Ctrough)
Measured: 0 hour (predose) on Day 1 of Cycles 1, 2, 4, 6, and 8
Number of Participants With Human Anti-Human Antibodies (HAHA)
Measured: Cycle 1, 2, 4, 6, 8 Day 1 at 0 hour (pre-dose)
Presence of Sensitivity Signature
Tumor molecular characteristics including but not limited to transcriptomic (RNA) signatures of sensitivity
Measured: 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
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.
Measured: Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.
Observed Serum Concentration of Circulating Protein
Measured: Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2013 (estimated)
- Study startOct 2013
- Primary completionJul 2014
- Study completionJul 2014
Why it stopped: See termination reason in detailed description.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01911273
- Sponsor's protocol ID
- A8471005
- Other IDs
- 2013-001426-26
- Status last verified
- Oct 2015
- First submitted
- 26 Jul 2013
- Last updated
- 28 Oct 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01911273
- Acronym / sponsor ID
- A8471005
- Conditions
- Carcinoma, Hepatocellular
- Keywords
- Hepatocellular carcinoma, monoclonal antibody, ALK-1, best supportive care
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: See termination reason in detailed description.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Oct 2013
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 30 Jul 2013 (estimated)
- Results
- Posted 29 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PF 03446962 plus best supportive care (BSC) | Experimental | Drug: PF-03446962, Other: Best Supportive Care |
| Placebo plus best supportive care (BSC) | Placebo comparator | Other: Placebo, Other: Best Supportive CarePlacebo, IV, every 2 weeks, until disease progression, patient refusal or unacceptable toxicity, whichever occurs first |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PF-03446962PF 03446962 7 mg/kg, IV, every 2 weeks, until disease progression, patient refusal or unacceptable toxicity, whichever occurs first | Drug | PF 03446962 plus best supportive care (BSC) |
| Best Supportive CareBSC may include medications and supportive measures deemed necessary to palliate disease related symptoms and improve quality of life | Other | PF 03446962 plus best supportive care (BSC) |
| PlaceboPlacebo will consist of Saline (0.9% w/v Sodium Chloride Injection, USP or NS) | Other | Placebo plus best supportive care (BSC) |
| Best Supportive CareBSC may include medications and supportive measures deemed necessary to palliate disease related symptoms and improve quality of life. | Other | Placebo plus best supportive care (BSC) |
Primary outcome
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.
12 secondary outcomes
Time to Tumor Progression (TTP)
Time frame: 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.
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.
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
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
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.
Maximum Serum Concentration (Cmax)
Time frame: 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
Number of Participants With Human Anti-Human Antibodies (HAHA)
Time frame: 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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PF-03446962 in people with Carcinoma, Hepatocellular, run by Pfizer at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Japan, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2015.