Ovarian cancer
Conditions
Interventions
Patients randomized to MEK162 treatment will take 45 mg orally (PO) twice daily
(BID) with water, continuously, starting on Day 1. Patients should be fasted 1
hour before and 1 hour after each dose.
Sponsors
Array BioPharma Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: •Written informed consent •Diagnosis of LGS carcinoma of the ovary, fallopian tube or primary peritoneum (invasive micropapillary serous carcinoma or invasive grade 1 serous carcinoma), confirmed histologically and verified by central pathology review.;•Recurrent or persistent measurable disease that has progressed (defined as radiological and/or clinical progression; an increase in cancer antigen [CA]-125 alone is not sufficient) on or after last therapy (i.e., chemotherapy, hormonal therapy, surgery) and is not amenable to potentially curative intent surgery, as determined by the patient's treating physician.;•Must have received at least 1 prior platinum-based chemotherapy regimen but have received no more than 3 lines of prior chemotherapy regimens, with no limit to the number of lines of prior hormonal therapy.;•Available archival tumor sample (excisional or core biopsy) for confirmation of LGS carcinoma diagnosis. If adequate archival tumor sample is not available, willingness to consent to tissue biopsy.;•Suitable for treatment with at least one of the physician's choice chemotherapy options (liposomal doxorubicin, paclitaxel or topotecan) as determined by the Investigator.;•Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.;•Other protocol-defined inclusion criteria exist.
Exclusion criteria
Exclusion criteria: •History or current evidence of retinal vein occlusion (RVO), or current risk factors for RVO.;•Prior therapy with a MEK or BRAF inhibitor.;•History of Gilbert's syndrome.;•Impaired cardiovascular function or clinically significant cardiovascular diseases.;•Uncontrolled or symptomatic brain metastases that are not stable or require steroids, are potentially life-threatening or have required radiation within 28 days prior to first dose of study treatment.;•Concomitant malignancies or previous malignancies with less than a 5-year disease-free interval at the time of first dose of study treatment; patients with adequately resected basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or ductal carcinoma in situ may be enrolled irrespective of the time of diagnosis.;•Known positive serology for the human immunodeficiency virus (HIV), active hepatitis B and/or active hepatitis C.;•Other protocol-defined exclusion criteria exist.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary: • Progression-free survival as determined by the blinded independent central review (BICR). The local Investigator assessments will be used as supportive analyses | — |
Secondary
| Measure | Time frame |
|---|---|
| • Overall survival • Objective response rate (ORR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 • Duration of response (DOR) • Disease control rate (DCR), defined as having achieved a best response of complete response (CR) or partial response (PR), or stable disease (SD) documented at Week 24 or later • Incidence and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03 • Changes in clinical laboratory parameters • Assessment by the quality-of-life (QOL) questionnaires European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-OV28 and Functional Assessment of Cancer Therapy (FACT)/Gynecologic Oncology Group (GOG)-Neurotoxicity (NTX) • Plasma concentration-time profiles and model-based PK parameters of MEK162 (and metabolite AR00426032, if feasible) in a subset of the patients randomized to receive MEK162 • During the crossover period, after failure of physician*s choice chemotherapy in the randomized period: o Progression-free survival as determined by local Investigator assessments o Objective response rate as defined by RECIST, Version 1.1 o Duration of response o Incidence and severity of AEs, graded according to the NCI CTCAE, Version 4.03 o Changes in clinical laboratory parameters o Assessment by the QOL questionnaires EORTC QLQ-C30, EORTC QLQ-OV28 and FACT/GOG-NTX Exploratory: • In tumor tissue, if available and as feasible: o Mutations in cancer-associated and chemotherapy-metabolism-related genes o Levels and activation states of apoptosis-related proteins and associated messenger ribonucleic acid (mRNA) transcripts o Levels and activation states of rat sarcoma viral oncogene (RAS)/v-Raf murine sarcoma viral oncogene (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway proteins, and associat | — |
Countries
Netherlands
Outcome results
None listed