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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01936363




Registration number
NCT01936363
Ethics application status
Date submitted
23/08/2013
Date registered
6/09/2013
Date last updated
12/12/2018

Titles & IDs
Public title
Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer
Scientific title
Phase II Randomized Double Blind Placebo Controlled Trial of Combination of Pimasertib With SAR245409 or of Pimasertib With SAR245409 Placebo in Subjects With Previously Treated Unresectable Low Grade Ovarian Cancer
Secondary ID [1] 0 0
2013-000902-40
Secondary ID [2] 0 0
EMR 200066_012
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pimasertib once daily
Treatment: Drugs - Pimasertib placebo
Treatment: Drugs - SAR245409 placebo
Treatment: Drugs - SAR245409
Treatment: Drugs - Pimasertib twice daily

Experimental: Pimasertib (once daily) plus SAR245409 -

Experimental: Pimasertib (twice daily) plus SAR245409 placebo -


Treatment: Drugs: Pimasertib once daily
Pimasertib administered as oral capsule at a dose of 60 milligram (mg) once daily until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.

Treatment: Drugs: Pimasertib placebo
Placebo matching Pimasertib administered once daily in evening until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.

Treatment: Drugs: SAR245409 placebo
Placebo matching SAR245409 administered once daily in morning until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.

Treatment: Drugs: SAR245409
SAR245409 administered as oral capsule at a dose of 70 milligram (mg) once daily until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.

Treatment: Drugs: Pimasertib twice daily
Pimasertib administered as oral capsule at a dose of 60 milligram (mg) twice daily until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Tumor Response - 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.
Timepoint [1] 0 0
From randomization until disease progression or death assessed every 8 weeks up to week 32, and thereafter every 12 weeks up to 52 months
Secondary outcome [1] 0 0
Progression-Free Survival - 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.
Timepoint [1] 0 0
Time from randomization until first observation of progressive disease or death, assessed up to 52 months
Secondary outcome [2] 0 0
Percentage of Participants With Disease Control - 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.
Timepoint [2] 0 0
Randomization until disease progression or death assessed every 8 weeks up to week 32, and thereafter every 12 weeks up to 52 months
Secondary outcome [3] 0 0
Overall Survival - 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.
Timepoint [3] 0 0
Time from randomization until death, assessed up to 52 months
Secondary outcome [4] 0 0
Health Related Quality of Life (HrQoL) Assessed Using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) - 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.
Timepoint [4] 0 0
Baseline up to disease progression or withdrawal, assessed up to 52 months
Secondary outcome [5] 0 0
Health Related Quality of Life (HrQoL) Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Ovarian-Specific Module Quality of Life Questionnaire Ovarian Cancer Module (QLQ-OV28) - 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.
Timepoint [5] 0 0
Baseline up to disease progression or withdrawal, assessed up to 52 months
Secondary outcome [6] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Treatment and Death - 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.
Timepoint [6] 0 0
First dose of study drug up to 52 months
Secondary outcome [7] 0 0
Maximum Plasma Concentration (Cmax) After Dose of Pimasertib and SAR245409
Timepoint [7] 0 0
Pre-dose Hour 0.5, 1.5, 4.5 8 post dose on Day 15, 29, 43
Secondary outcome [8] 0 0
Area Under the Curve (AUC) After Dose of Pimasertib and SAR245409
Timepoint [8] 0 0
Pre-dose Hour 0.5, 1.5, 4.5 8 post dose on Day 15, 29, 43
Secondary outcome [9] 0 0
Molecular Alterations in MAPK and/or PI3K Signaling Pathway Components/Modulators in Tumor Tissue and Blood
Timepoint [9] 0 0
Screening visit (day -28 to 1)

Eligibility
Key inclusion criteria
- The female participant had a diagnosis of one of the following: a) low-grade serous
ovarian or peritoneal carcinoma, or grade 1 serous ovarian or peritoneal carcinoma or
well-differentiated serous ovarian or peritoneal carcinoma or b) serous borderline
ovarian or peritoneal tumor, ovarian or peritoneal tumor of low-malignant potential,
ovarian or peritoneal atypical proliferative serous tumor that recurs as low grade
serous carcinoma or has invasive peritoneal implants

- The participant had at least one prior line of systemic therapy and had a tumor, which
was not amenable to potentially curative surgical resection

- The participant had measurable disease by Response Evaluation Criteria in Solid Tumors
(RECIST) v1.1

- The participant had read and understood the written informed consent form (ICF) and
was willing and able to gave informed consent, fully understood the requirements of
the trial and was willing to comply with all trial visits and assessments, including
completion of patient-reported measures. Consent must be given before any trial
related activities

- Women of childbearing potential must had a negative serum pregnancy test at the
screening visit

- Women of childbearing potential must be willing to avoid pregnancy by using an
adequate method of contraception for 2 weeks prior to screening, during and at least 3
months after the last dose of trial medication

- Other protocol defined inclusion criteria may apply
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- The participant had previously been treated with a PI3K inhibitor and taken off
treatment due to treatment related AEs

- The participant had been previously treated with a Mitogen-activated
protein/extracellular signal-regulated kinase (MEK) inhibitor

- Any anti-cancer therapy or treatment incorporating chemotherapy, immunotherapy,
hormonal therapy, or biologic therapy within 28 days of the start of trial treatment
or within 5 times the half-life of such treatment, whichever was shorter. Treatment
with nitrosoureas or mitomycin C were exceptions to this for which a treatment
interval of at least 6 weeks was required

- The participant had not recovered from toxicity due to prior therapy to baseline level
or National Cancer Institute Common Terminology Criteria for Adverse Events Version
4.0 (NCI CTCAE v4.0) Grade 1 or less (except alopecia). Residual chemotherapy-induced
neuropathy grade less than equal to (<=) 2 was permitted

- The participant had poor organ and marrow function as defined in the protocol

- The participant had creatine phosphokinase (CPK) elevation NCI CTCAE grade greater
than equal to (>=) 2, and/or a previous history of myositis or rhabdomyolysis

- The participant had difficulty swallowing, malabsorption or other chronic
gastrointestinal disease or conditions that may hamper compliance and/or absorption of
the trial drug. Participants requiring total parenteral nutrition were to be excluded

- The participant had a history of delayed healing/open wounds or diabetic ulcers

- The participant had a history of congestive heart failure, unstable angina, myocardial
infarction, cardiac conduction abnormalities including Fridericia corrected QT
interval (QTcF) prolongation of > 480 milliseconds (ms) or a pacemaker, clinically
relevant impaired cardiovascular function (New York Heart Association (NYHA) class
III/IV) or stroke within 3 months prior to enrollment

- The participant had a history of retinal degenerative disease (hereditary retinal
degeneration or age-related macular degeneration), uveitis or retinal vein occlusion
(RVO), or had other relevant abnormalities identified on screening ophthalmologic
examination, which might increase the risk of serous retinal detachment (SRD) or RVO

- The participant had a history of uncontrolled intercurrent illness including but not
limited to an active infection, hypertension, or uncontrolled diabetes (e.g.
glycosylated hemoglobin >= 8 percent [%]) that would limit compliance with treatment
requirements

- Any previous malignancy treated with curative intent and the participant had been
disease free for less than 5 years prior to randomization, with exception of
carcinoma-in-situ of the cervix, squamous carcinoma of the skin, basal cell carcinoma
of the skin

- Other protocol defined exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Research site - Northmead
Recruitment hospital [2] 0 0
Research site - Greenslopes
Recruitment hospital [3] 0 0
Research site - Subiaco
Recruitment postcode(s) [1] 0 0
2152 - Northmead
Recruitment postcode(s) [2] 0 0
4120 - Greenslopes
Recruitment postcode(s) [3] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Montana
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Belgium
State/province [13] 0 0
Kortrijk
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
France
State/province [17] 0 0
Gironde
Country [18] 0 0
Poland
State/province [18] 0 0
Chorzow
Country [19] 0 0
Spain
State/province [19] 0 0
Baleares
Country [20] 0 0
Spain
State/province [20] 0 0
Madrid
Country [21] 0 0
Spain
State/province [21] 0 0
Sevilla
Country [22] 0 0
Spain
State/province [22] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
EMD Serono
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Sanofi
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a double blind, randomized, placebo-controlled, 2-arm, Phase 2 trial investigating
the efficacy and safety of combination therapy of pimasertib plus SAR245409 and pimasertib
placebo administered once per day compared to pimasertib administered twice per day plus
SAR245409 placebo administered once per day in participants with previously treated
unresectable low-grade serous ovarian or peritoneal carcinoma or serous borderline ovarian or
peritoneal tumors.
Trial website
https://clinicaltrials.gov/show/NCT01936363
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
Merck KGaA, Darmstadt, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications