Recurrent or persistent low-grade serous (LGS) carcinomas of the ovary, fallopian tube or primary peritoneum MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: binimetinib
Product Code: MEK162
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BINIMETINIB
CAS Number: 6061
Sponsors
Array BioPharma Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
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 |
|---|---|
| Main Objective: To determine whether treatment with MEK162 prolongs Progression-free survival as compared to physician’s choice of selected chemotherapies (liposomal doxorubicin, paclitaxel and topotecan) in patients with recurrent or persistent low-grade serous carcinomas of the ovary, fallopian tube or primary peritoneum; Secondary Objective: Obtain additional estimates of the efficacy (including overall survival [OS]) of MEK162 vs. physician’s choice of selected chemotherapies • Characterize the safety profile of MEK162 vs. physician’s choice of selected chemotherapies • Assess the effect on global health status of MEK162 vs. physician’s choice of selected chemotherapies • Characterize the plasma pharmacokinetics (PK) of MEK162 in this patient population • During the crossover period, after failure of physician’s choice chemotherapy in the randomized period: o Assess the efficacy of MEK162 o Characterize the safety profile of MEK162 o Assess the effect on global health status of MEK162 ; Primary end point(s): • Progression-free survival as determined by the blinded independent central review (BICR). The local Investigator assessments will be used as supportive analyses. As of Protocol Version 6 (date 15 March 2017), BICR review of tumor assessments will no longer be performed; tumor assessments in both the randomized and crossover periods will be conducted by the study sites according to institutional standards. Results of tumor assessments will be retained in patient files only and no longer be entered into the eCRFs. As of Protocol Version 6 (date 15 March 2017), all patients will return for a 30-Day Safety Follow-up Visit approximately 30 days after the last dose of study drug for safety. After completion of this visit, all patients will end their participation in the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival • Objective response rate (ORR) as defined by the Response Evaluation Criteria in Solid Tumorso Assessment by the QOL questionnaires EORTC QLQ-C30, EORTC QLQ-OV28 and FACT/GOG-NTX (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 parameterso Assessment by the QOL questionnaires EORTC QLQ-C30, EORTC QLQ-OV28 and FACT/GOG-NTX ; Timepoint(s) of evaluation of this end point: Overall Survival: All patients will be followed for survival until withdrawal of consent, lost to follow-up or death; or until the st | — |
Countries
Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Hungary, Ireland, Italy, Luxembourg, Netherlands, Norway, Poland, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactFranklin Vairinhos
Array BioPharma Inc.
Outcome results
None listed