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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
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
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
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)
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)
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
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
Sex
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
30/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/11/2017
Sample size
Target
Accrual to date
Final
65
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/study/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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01936363