Clinical trial NCT01936363: Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Ovarian Cancer
Pimasertib
Placebo
SAR245409
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2013-09-06
Enrollment: 65
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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

Primary outcomes:
measure: Objective Tumor Response
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
Secondary outcomes:
measure: Progression-Free Survival
timeFrame: Time from randomization until first observation of progressive disease or death, assessed up to 52 months
measure: Percentage of Participants With Disease Control
timeFrame: Randomization until disease progression or death assessed every 8 weeks up to week 32, and thereafter every 12 weeks up to 52 months
measure: Overall Survival
timeFrame: Time from randomization until death, assessed up to 52 months
measure: Health Related Quality of Life (HrQoL) Assessed Using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30)
timeFrame: Baseline up to disease progression or withdrawal, assessed up to 52 months
measure: 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)
timeFrame: Baseline up to disease progression or withdrawal, assessed up to 52 months
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Treatment and Death
timeFrame: First dose of study drug up to 52 months
measure: Maximum Plasma Concentration (Cmax) After Dose of Pimasertib and SAR245409
timeFrame: Pre-dose Hour 0.5, 1.5, 4.5 8 post dose on Day 15, 29, 43
measure: Area Under the Curve (AUC) After Dose of Pimasertib and SAR245409
timeFrame: Pre-dose Hour 0.5, 1.5, 4.5 8 post dose on Day 15, 29, 43
measure: Molecular Alterations in MAPK and/or PI3K Signaling Pathway Components/Modulators in Tumor Tissue and Blood
timeFrame: Screening visit (day -28 to 1)
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Research site
state: Georgia
city: Chicago
country: United States
facility: Research site
state: Illinois
city: Indianapolis
country: United States
facility: Research site
state: Indiana
city: Silver Spring
country: United States
facility: Research site
state: Maryland
city: Boston
country: United States
facility: Research site
state: Massachusetts
city: Boston
country: United States
facility: Research site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research site
state: Michigan
city: Detroit
country: United States
facility: Research site
state: Michigan
city: Kansas City
country: United States
facility: Research site
state: Missouri
city: Saint Louis
country: United States
facility: Research site
state: Missouri
city: Kalispell
country: United States
facility: Research site
state: Montana
city: New York
country: United States
facility: Research site
state: New York
city: Cincinnati
country: United States
facility: Research site
state: Ohio
city: Columbus
country: United States
facility: Research site
state: Ohio
city: Middletown
country: United States
facility: Research site
state: Ohio
city: Nashville
country: United States
facility: Research site
state: Tennessee
city: Houston
country: United States
facility: Research site
state: Texas
city: Northmead
country: Australia
facility: Research site
state: New South Wales
city: Greenslopes
country: Australia
facility: Research site
state: Queensland
city: Subiaco
country: Australia
facility: Research site
state: Western Australia
city: Kortrijk
country: Belgium
facility: Research site
city: Leuven
country: Belgium
facility: Research site
city: Hamilton
country: Canada
facility: Research site
state: Ontario
city: Toronto
country: Canada
facility: Research site
state: Ontario
city: Montreal
country: Canada
facility: Research site
state: Quebec
city: Montreal
country: Canada
facility: Research site
state: Quebec
city: Quebec
country: Canada
facility: Research site
city: Bordeaux Cedex
country: France
facility: Research site
state: Gironde
city: Chorzow
country: Poland
facility: Research site
city: Palma Mallorca
country: Spain
facility: Research site
state: Baleares
city: Madrid
country: Spain
facility: Research site
city: Madrid
country: Spain
facility: Research site
city: Sevilla
country: Spain
facility: Research site
city: Valencia
country: Spain
facility: Research site
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: