Trial Outcomes & Findings for 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 (NCT NCT01911273)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

From first randomization to date of death from any cause, whichever came first, assessed up to 24 months after last participant randomization

Results posted on

2015-10-28

Participant Flow

Only 3 participants were enrolled into this study as of termination date. One participant was assigned to receive PF-03446962 plus best supportive care (BSC) treatment and 2 participants were assigned to receive only BSC treatment.

Participant milestones

Participant milestones
Measure	PF-03446962 Plus BSC PF-03446962 7 milligram per kilogram (mg/kg) was administered intravenously (IV) as 1-hour infusion every two weeks (q2w) plus BSC	BSC Alone BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.
Overall Study STARTED	1	2
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	PF-03446962 Plus BSC PF-03446962 7 milligram per kilogram (mg/kg) was administered intravenously (IV) as 1-hour infusion every two weeks (q2w) plus BSC	BSC Alone BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.
Overall Study Progression of Disease	1	0
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PF-03446962 Plus BSC n=1 Participants PF-03446962 7 mg/kg was administered IV as 1-hour infusion q2w plus BSC	BSC Alone n=2 Participants BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.	Total n=3 Participants Total of all reporting groups
Age, Customized 18 to 44 Years	1 Participants 0.0 • n=5 Participants	0 Participants NA • n=7 Participants	1 Participants n=5 Participants
Age, Customized 45 to 64 Years	0 Participants NA • n=5 Participants	2 Participants 6.4 • n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first randomization to date of death from any cause, whichever came first, assessed up to 24 months after last participant randomization

Population: Full analysis set (FAS) included all randomized participants regardless of what treatment, if any, was received.

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.

Outcome measures

Outcome measures
Measure	PF-03446962 Plus BSC n=1 Participants PF-03446962 7 mg/kg was administered IV as 1-hour infusion q2w plus BSC	BSC Alone n=2 Participants BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.
Overall Survival (OS)	NA Months Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading	NA Months Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading

SECONDARY outcome

Timeframe: Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization.

Population: FAS included all randomized participants regardless of what treatment, if any, was received.

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).

Outcome measures

Outcome measures
Measure	PF-03446962 Plus BSC n=1 Participants PF-03446962 7 mg/kg was administered IV as 1-hour infusion q2w plus BSC	BSC Alone n=2 Participants BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.
Time to Tumor Progression (TTP)	NA Months Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading	NA Months Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading

SECONDARY outcome

Timeframe: Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization.

Population: FAS included all randomized participants regardless of what treatment, if any, was received.

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.

Outcome measures

Outcome measures
Measure	PF-03446962 Plus BSC n=1 Participants PF-03446962 7 mg/kg was administered IV as 1-hour infusion q2w plus BSC	BSC Alone n=2 Participants BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.
Progression-Free Survival (PFS)	NA Months Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading	NA Months Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading

SECONDARY outcome

Timeframe: Screening and every 8 weeks by calendar thereafter, up to 24 months after last participant randomization.

Population: FAS included all randomized participants regardless of what treatment, if any, was received.

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.

Outcome measures

Outcome measures
Measure	PF-03446962 Plus BSC n=1 Participants PF-03446962 7 mg/kg was administered IV as 1-hour infusion q2w plus BSC	BSC Alone n=2 Participants BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.
Objective Response Rate (ORR) - Percentage of Participants With Objective Response	NA Percentage of Participants Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading	NA Percentage of Participants Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading

SECONDARY outcome

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

Population: Subgroup of participants with objective response. Since objective response was not assessed in any of the participants, ideally the number of participants analyzed field should be 0 and the reason was insufficient data available to conduct adequate analysis due to premature termination of the study.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

Population: FAS included all randomized participants regardless of what treatment, if any, was received.

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.

Outcome measures

Outcome measures
Measure	PF-03446962 Plus BSC n=1 Participants PF-03446962 7 mg/kg was administered IV as 1-hour infusion q2w plus BSC	BSC Alone n=2 Participants BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.
Percentage of Participants With Disease Control Rate (DCR) at 16 Weeks	NA Percentage of Participants Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading	NA Percentage of Participants Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading

SECONDARY outcome

Timeframe: Screening, Cycle 1 Day1,8; Cycle >=2 Day1; End of treatment, survival follow-up up to 24 months after last participant randomization.

Population: FAS included all randomized participants regardless of what treatment, if any, was received.

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.

Outcome measures

Outcome measures
Measure	PF-03446962 Plus BSC n=1 Participants PF-03446962 7 mg/kg was administered IV as 1-hour infusion q2w plus BSC	BSC Alone n=2 Participants BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.
Change From Baseline in Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire (FACT-Hep)	NA Units on scale Standard Deviation NA Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading	NA Units on scale Standard Deviation NA Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading

SECONDARY outcome

Timeframe: 1 hour (after start of infusion) on Day1 of Cycles 1, 2, 4, 6, and 8

Population: The pharmacokinetic (PK) concentration set consisted of all participants who were treated and had at least one concentration on at least 1 day of PK assessment.

Outcome measures

Outcome measures
Measure	PF-03446962 Plus BSC n=1 Participants PF-03446962 7 mg/kg was administered IV as 1-hour infusion q2w plus BSC	BSC Alone BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.
Maximum Serum Concentration (Cmax)	NA microgram per milliliter (mcg/mL) Standard Error NA Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading	—

SECONDARY outcome

Timeframe: 0 hour (predose) on Day 1 of Cycles 1, 2, 4, 6, and 8

Population: The PK concentration set consisted of all participants who were treated and had at least one concentration on at least 1 day of PK assessment.

Outcome measures

Outcome measures
Measure	PF-03446962 Plus BSC n=1 Participants PF-03446962 7 mg/kg was administered IV as 1-hour infusion q2w plus BSC	BSC Alone BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.
Trough Serum Concentration of PF-03446962 (Ctrough)	NA mcg/mL Standard Error NA Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading	—

SECONDARY outcome

Timeframe: Cycle 1, 2, 4, 6, 8 Day 1 at 0 hour (pre-dose)

Population: The immunogenicity assessment consisted of all participants who had at least 1 sample on at least 1 day of immunogenicity assessment.

Outcome measures

Outcome measures
Measure	PF-03446962 Plus BSC n=1 Participants PF-03446962 7 mg/kg was administered IV as 1-hour infusion q2w plus BSC	BSC Alone BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.
Number of Participants With Human Anti-Human Antibodies (HAHA)	NA Participants Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.

Population: FAS included all randomized participants regardless of what treatment, if any, was received.

Tumor molecular characteristics including but not limited to transcriptomic (RNA) signatures of sensitivity

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.

Population: FAS included all randomized participants regardless of what treatment, if any, was received.

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.

Outcome measures

Outcome measures
Measure	PF-03446962 Plus BSC n=1 Participants PF-03446962 7 mg/kg was administered IV as 1-hour infusion q2w plus BSC	BSC Alone BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.
Ratio to Baseline of Serum Circulating Protein Concentration	NA Percentage Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (before infusion), Cycle 4 Day 1 (before infusion), at disease progression/participant withdrawal.

Population: FAS included all randomized participants regardless of what treatment, if any, was received.

Outcome measures

Outcome measures
Measure	PF-03446962 Plus BSC n=1 Participants PF-03446962 7 mg/kg was administered IV as 1-hour infusion q2w plus BSC	BSC Alone BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.
Observed Serum Concentration of Circulating Protein	NA mcg/mL Due to the early termination of the study the incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading	—

Adverse Events

PF-03446962 Plus BSC

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

BSC Alone

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	PF-03446962 Plus BSC n=1 participants at risk PF-03446962 7 mg/kg was administered IV as 1-hour infusion q2w plus BSC	BSC Alone n=2 participants at risk BSC might vary depending on the participant's signs and symptoms, site current practice, and country practice and might include medications and supportive measures deemed necessary to palliate disease-related symptoms and improve quality of life.
Infections and infestations Gastroenteritis	100.0% 1/1 • Number of events 1 • Day 1 up to 28 days after the last administration of study medication. Three participants were assigned to receive study treatment, as of study termination date. One participant was assigned to receive PF-03446962 plus BSC treatment and discontinued due to progression of disease; 2 were assigned to receive BSC only treatment and discontinued due to withdrawal of consent.	0.00% 0/2 • Day 1 up to 28 days after the last administration of study medication. Three participants were assigned to receive study treatment, as of study termination date. One participant was assigned to receive PF-03446962 plus BSC treatment and discontinued due to progression of disease; 2 were assigned to receive BSC only treatment and discontinued due to withdrawal of consent.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	100.0% 1/1 • Number of events 2 • Day 1 up to 28 days after the last administration of study medication. Three participants were assigned to receive study treatment, as of study termination date. One participant was assigned to receive PF-03446962 plus BSC treatment and discontinued due to progression of disease; 2 were assigned to receive BSC only treatment and discontinued due to withdrawal of consent.	0.00% 0/2 • Day 1 up to 28 days after the last administration of study medication. Three participants were assigned to receive study treatment, as of study termination date. One participant was assigned to receive PF-03446962 plus BSC treatment and discontinued due to progression of disease; 2 were assigned to receive BSC only treatment and discontinued due to withdrawal of consent.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator will provide manuscripts, abstracts, or the full text of any other intended disclosure (poster presentation, invited speaker or guest lecturer presentation, etc.) to Pfizer at least 30 days before they are submitted for publication or otherwise disclosed. If any patent action is required to protect intellectual property rights, Investigator agrees to delay the disclosure for a period not to exceed an additional 60 days.
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Restriction type: OTHER