Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer

Merck KGaA (EMD Serono)

Status and phase

Completed

Phase 2

Conditions

Ovarian Cancer

Treatments

Drug: Pimasertib placebo

Drug: SAR245409

Drug: Pimasertib once daily

Drug: SAR245409 placebo

Drug: Pimasertib twice daily

Study type

Interventional

Funder types

Industry

Identifiers

NCT01936363

2013-000902-40 (EudraCT Number)

EMR 200066_012

Details and patient eligibility

About

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.

Enrollment

65 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

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