Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer
Condition: Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: Pimasertib once daily; Pimasertib placebo; SAR245409 placebo; SAR245409; Pimasertib twice daily
Intervention description: 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.; Placebo matching Pimasertib administered once daily in evening until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.; Placebo matching SAR245409 administered once daily in morning until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.; 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.; 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 MeSH terms: Niacinamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 65.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ovarian Cancer; Pimasertib; Placebo; SAR245409

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