Trial Outcomes & Findings for Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer (NCT NCT01936363)

NCT ID: NCT01936363

Last Updated: 2018-12-12

Results Overview

Objective tumor response was defined as the presence of at least one Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to more than (\<) 10 millimeter (mm). Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

65 participants

Primary outcome timeframe

From randomization until disease progression or death assessed every 8 weeks up to week 32, and thereafter every 12 weeks up to 52 months

Results posted on

2018-12-12

Participant Flow

First/last participants (informed consent): Sep 2013/Oct 2014. Clinical data cut off: Jan 2018.

Participant milestones

Participant milestones
Measure	Pimasertib (Once Daily) Plus SAR245409 Participants received Pimasertib oral capsule at a dose of 60 milligram (mg) once daily along with SAR245409 oral capsule at a dose of 70 mg once daily and placebo matching to pimasertib in evening until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.	Pimasertib (Twice Daily) Plus SAR245409 Placebo Participants received pimasertib oral capsule at a dose of 60 mg twice daily along with placebo matching to SAR245409 once daily in morning until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.
Overall Study STARTED	32	33
Overall Study COMPLETED	32	33
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pimasertib (Once Daily) Plus SAR245409 n=32 Participants Participants received Pimasertib oral capsule at a dose of 60 milligram (mg) once daily along with SAR245409 oral capsule at a dose of 70 mg once daily and placebo matching to pimasertib in evening until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.	Pimasertib (Twice Daily) Plus SAR245409 Placebo n=33 Participants Participants received pimasertib oral capsule at a dose of 60 mg twice daily along with placebo matching to SAR245409 once daily in morning until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.	Total n=65 Participants Total of all reporting groups
Age, Continuous	47.3 years STANDARD_DEVIATION 14.07 • n=5 Participants	50.6 years STANDARD_DEVIATION 16.39 • n=7 Participants	49.0 years STANDARD_DEVIATION 15.26 • n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	33 Participants n=7 Participants	65 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization until disease progression or death assessed every 8 weeks up to week 32, and thereafter every 12 weeks up to 52 months

Population: ITT analysis set included all participants who had been randomized.

Outcome measures

Outcome measures
Measure	Pimasertib (Once Daily) Plus SAR245409 n=32 Participants Participants received Pimasertib oral capsule at a dose of 60 milligram (mg) once daily along with SAR245409 oral capsule at a dose of 70 mg once daily and placebo matching to pimasertib in evening until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.	Pimasertib (Twice Daily) Plus SAR245409 Placebo n=33 Participants Participants received pimasertib oral capsule at a dose of 60 mg twice daily along with placebo matching to SAR245409 once daily in morning until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.
Objective Tumor Response	12.5 percentage of participants Interval 3.5 to 29.0	12.1 percentage of participants Interval 3.4 to 28.2

SECONDARY outcome

Timeframe: Time from randomization until first observation of progressive disease or death, assessed up to 52 months

Population: ITT analysis set included all participants who had been randomized.

PFS defined as time from randomization to first documentation of objective tumor progression.CR:Disappearance of all target lesions.Any pathological lymph nodes(whether target or non-target)must have reduction in short axis to\<10 mm.PR:At least 30% decrease in sum of diameters of target lesions,taking as reference baseline sum diameters.PD:At least a 20% increase in sum of diameters of target lesions,taking as reference smallest sum on study.In addition to relative increase of 20%,the sum also demonstrate absolute increase of at least 5 mm.SD:Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD,taking as reference smallest sum diameters while on study. PFS calculated as(Months)=first event date minus randomization or first dose date plus 1.Median PFS was computed using Kaplan-Meier estimates (product-limit estimates) and was presented with 95% confidence interval.The confidence intervals for median was calculated according to Brookmeyer and Crowley.

Outcome measures

Outcome measures
Measure	Pimasertib (Once Daily) Plus SAR245409 n=32 Participants Participants received Pimasertib oral capsule at a dose of 60 milligram (mg) once daily along with SAR245409 oral capsule at a dose of 70 mg once daily and placebo matching to pimasertib in evening until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.	Pimasertib (Twice Daily) Plus SAR245409 Placebo n=33 Participants Participants received pimasertib oral capsule at a dose of 60 mg twice daily along with placebo matching to SAR245409 once daily in morning until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.
Progression-Free Survival	9.99 months Interval 3.42 to 15.21	12.71 months Interval 4.21 to The upper limit of 95% Confidence Interval for PFS could not be calculated because this upper limit was not reached due to limited number of events.

SECONDARY outcome

Timeframe: Randomization until disease progression or death assessed every 8 weeks up to week 32, and thereafter every 12 weeks up to 52 months

Population: ITT analysis set included all participants who had been randomized.

Disease control as per RECIST v.1.1 was defined as the proportion of participants with stable disease (SD), for at least 16 weeks, PR or CR according to RECIST v1.1 criteria. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: At least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters). CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.

Outcome measures

Outcome measures
Measure	Pimasertib (Once Daily) Plus SAR245409 n=32 Participants Participants received Pimasertib oral capsule at a dose of 60 milligram (mg) once daily along with SAR245409 oral capsule at a dose of 70 mg once daily and placebo matching to pimasertib in evening until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.	Pimasertib (Twice Daily) Plus SAR245409 Placebo n=33 Participants Participants received pimasertib oral capsule at a dose of 60 mg twice daily along with placebo matching to SAR245409 once daily in morning until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.
Percentage of Participants With Disease Control	50.0 percentage of participants Interval 31.9 to 68.1	39.4 percentage of participants Interval 22.9 to 57.9

SECONDARY outcome

Timeframe: Time from randomization until death, assessed up to 52 months

Population: ITT analysis set included all participants who had been randomized.

Overall survival (OS) was defined as the time (in months) from randomization to death. Data has been presented in terms of number participants who died and number of censored participants.

Outcome measures

Outcome measures
Measure	Pimasertib (Once Daily) Plus SAR245409 n=32 Participants Participants received Pimasertib oral capsule at a dose of 60 milligram (mg) once daily along with SAR245409 oral capsule at a dose of 70 mg once daily and placebo matching to pimasertib in evening until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.	Pimasertib (Twice Daily) Plus SAR245409 Placebo n=33 Participants Participants received pimasertib oral capsule at a dose of 60 mg twice daily along with placebo matching to SAR245409 once daily in morning until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.
Overall Survival Number for censored	24 Participants	27 Participants
Overall Survival Number of deaths	8 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline up to disease progression or withdrawal, assessed up to 52 months

Population: Data was not collected for this outcome because as per Protocol Amendment 4 (dated 13 March 2015), the collection of patient-reported health-related quality of life outcomes was discontinued.

EORTC QLQ-C30 is a 30-item questionnaire comprising of five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea/vomiting), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact), and a global quality of life (QoL) scale summarized from two 7-point scales (overall QoL and overall general health). Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and the individual single-items ranged in score from 0 to 100. A high scale score represents a higher response level. High score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to disease progression or withdrawal, assessed up to 52 months

EORTC QLQ-OV28 assesses disease and treatment-related symptoms of ovarian cancer. The 28-item module comprises of 6 symptom scales (abdominal/gastrointestinal symptoms, peripheral neuropathy, other chemotherapy side-effects, hormonal symptoms, body image, attitude to disease and treatment), and sexual functioning. All of the scales and the individual single-items ranged in score from 0 to 100. Higher scores indicate a better quality of life.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: First dose of study drug up to 52 months

Population: Safety population (SAF) analysis set included all participants who received at least one dose of any trial treatment.

TEAEs, Serious TEAEs and AEs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0. An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A Serious Adverse Event was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to data cut-off that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure	Pimasertib (Once Daily) Plus SAR245409 n=32 Participants Participants received Pimasertib oral capsule at a dose of 60 milligram (mg) once daily along with SAR245409 oral capsule at a dose of 70 mg once daily and placebo matching to pimasertib in evening until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.	Pimasertib (Twice Daily) Plus SAR245409 Placebo n=32 Participants Participants received pimasertib oral capsule at a dose of 60 mg twice daily along with placebo matching to SAR245409 once daily in morning until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Treatment and Death Death	2 Participants	3 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Treatment and Death TEAE	32 Participants	32 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Treatment and Death Serious TEAE	16 Participants	18 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Treatment and Death TEAE leading to discontinuation of study treatment	16 Participants	12 Participants

SECONDARY outcome

Timeframe: Pre-dose Hour 0.5, 1.5, 4.5 8 post dose on Day 15, 29, 43

Population: As per changed in planned analysis the outcome measure related to pharmacokinetic parameters was not assessed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose Hour 0.5, 1.5, 4.5 8 post dose on Day 15, 29, 43

Population: As per changed in planned analysis the outcome measure related to pharmacokinetic parameters was not assessed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Screening visit (day -28 to 1)

Population: As per changed in planned analysis the outcome measure related to pharmacodynamics parameters was not assessed.

Outcome measures

Outcome data not reported

Adverse Events

Pimasertib (Once Daily) Plus SAR245409

Serious events: 16 serious events

Other events: 32 other events

Deaths: 0 deaths

Pimasertib (Twice Daily) Plus SAR245409 Placebo

Serious events: 18 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Merck KGaA Communication Center

Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER