Overview

This trial is active, not recruiting.

Condition ovarian cancer
Treatments pimasertib once daily, pimasertib placebo, sar245409 placebo, sar245409, pimasertib twice daily
Phase phase 2
Targets PI3K, mTOR
Sponsor EMD Serono
Collaborator Sanofi
Start date September 2013
End date May 2015
Trial size 65 participants
Trial identifier NCT01936363, 2013-000902-40, EMR 200066_012

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 subjects with previously treated unresectable low-grade serous ovarian or peritoneal carcinoma or serous borderline ovarian or peritoneal tumors.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
pimasertib once daily
Pimasertib will be 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 comes first.
pimasertib placebo
Placebo matching Pimasertib will be administered once daily in evening until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever comes first.
sar245409
SAR245409 will be 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 comes first.
(Experimental)
sar245409 placebo
Placebo matching SAR245409 will be administered once daily in morning until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever comes first.
pimasertib twice daily
Pimasertib will be 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 comes first.

Primary Outcomes

Measure
Objective tumor response defined as complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1) as determined by the investigator
time frame: up to 2.5 years

Secondary Outcomes

Measure
Progression-free survival
time frame: Time from randomization until first observation of progressive disease or death, when death occurs within 12 weeks of the last tumor assessment (whichever comes first), up to 30 days after last treatment
Percentage of subjects with disease control according to RECIST v.1.1
time frame: Baseline, Week 8, 16, 24 and 32, and thereafter every 12 weeks up to 30 days after last treatment
Overall survival time
time frame: Time from randomization to death up to 12 months after last subject randomized
Health Related Quality of Life (HrQoL) assessed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) Version 3.0
time frame: Day 1 and Day 29, and Week 8, 16, 24 and 32, and thereafter every 12 weeks up to 30 days after last treatment
HrQoL assessed using EORTC QLQ-C30 Version 3.0 - ovarian-specific module QLQ-OV28
time frame: Day 1 and Day 29, and Week 8, 16, 24 and 32, and thereafter every 12 weeks up to 30 days after last treatment
Number of Subjects with Treatment Emergent Adverse Events (TEAEs), Adverse Events (AEs) of special interest, Serious Adverse Events (SAEs), discontinuation of treatment due to TEAEs, death
time frame: Baseline up to 30 days after last treatment
Maximum Plasma Concentration (Cmax) After Dose of pimasertib and SAR245409
time frame: pre-dosing to 0.5, 1.5, 4.5 and 8 hours after the morning dose at day 15, 29, 43
Area under the curve (AUC) After Dose of pimasertib and SAR245409
time frame: pre-dosing to 0.5, 1.5, 4.5 and 8 hours after the morning dose at day 15, 29, 43
Molecular Alterations in MAPK and/or PI3K signaling pathway components/modulators in tumor tissue and blood
time frame: Screening visit (day -28 to 1)

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - The female subject has 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 subject had at least one prior line of systemic therapy and has a tumor, which is not amenable to potentially curative surgical resection. - The subject has measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. - The subject is at least 18 years old. - The subject has read and understood the written informed consent form (ICF) and is willing and able to give informed consent, fully understands the requirements of the trial and is 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 have 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 subject has previously been treated with a PI3K inhibitor and taken off treatment due to treatment related AEs. - The subject has 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 is shorter. Treatment with nitrosoureas or mitomycin C are exceptions to this for which a treatment interval of at least 6 weeks is required - The subject has 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 <= 2 is permitted. - The subject has poor organ and marrow function as defined in the protocol. - The subject has creatine phosphokinase (CPK) elevation NCI CTCAE grade >=2, and/or a previous history of myositis or rhabdomyolysis. - The subject has difficulty swallowing, malabsorption or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the trial drug. Subjects requiring total parenteral nutrition are to be excluded. - The subject has a history of delayed healing/open wounds or diabetic ulcers. - The subject has a history of congestive heart failure, unstable angina, myocardial infarction, cardiac conduction abnormalities including Fridericia corrected QT interval (QTcF) prolongation of > 480ms 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 subject has a history of retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), uveitis or retinal vein occlusion (RVO), or has other relevant abnormalities identified on screening opthalmologic examination, which may increase the risk of serous retinal detachment (SRD) or RVO. - The subject has a history of uncontrolled intercurrent illness including but not limited to an active infection, hypertension, or uncontrolled diabetes (e.g. glycosylated hemoglobin >= 8%) that would limit compliance with treatment requirements. - Any previous malignancy treated with curative intent and the subject has 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.

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by EMD Serono.