A Study of MEK162 vs. Physician's Choice Chemotherapy in Patients With Low-grade Serous Ovarian, Fallopian Tube or Peritoneal Cancer
Condition: Low-grade Serous Ovarian Cancer; Low-grade Serous Fallopian Tube Cancer; Low-grade Serous Peritoneal Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms
Intervention: MEK162, MEK inhibitor; oral; Physician's choice chemotherapy
Intervention description: multiple dose, single schedule; Patients will receive one of the following chemotherapies as determined by the physician:
Liposomal doxorubicin, anthracycline antibiotic; intravenous (multiple dose, single schedule)
Paclitaxel, mitotic inhibitor; intravenous (multiple dose, single schedule)
Topotecan, topoisomerase 1 inhibitor; intravenous (multiple dose, single schedule)
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 341.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The MILO Study (MEK Inhibitor in Low-grade Serous Ovarian Cancer) is a Phase 3 study during
      which patients with recurrent or persistent low-grade serous (LGS) carcinomas of the ovary,
      fallopian tube or primary peritoneum will receive either investigational study drug MEK162 or
      a chemotherapy chosen by the physician (liposomal doxorubicin, paclitaxel or topotecan).
      Patients will be followed to compare the effectiveness of the study drug to that of the
      selected chemotherapies. Patients may be eligible to crossover from physician's choice
      chemotherapy to MEK162 if they meet certain inclusion criteria including centrally confirmed
      disease progression. Approximately 360 patients from North America, Europe and Australia will
      be enrolled in this study.
    

Eligibility criteria:

        Key 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. Front-line therapy may include neoadjuvant
             and adjuvant therapy and will be counted as 1 prior systemic regimen. Biological
             therapy (e.g. bevacizumab) administered as a single agent is considered a prior
             systemic regimen and not a prior chemotherapy regimen. Maintenance therapy is not
             considered its own regimen but should be included with the regimen that it follows.

          -  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.

          -  Additional criteria exist.

        Key Exclusion Criteria:

          -  History or current evidence of retinal vein occlusion (RVO) or current risk factors
             for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity
             or hypercoagulability syndromes).

          -  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.

          -  Prior randomization into this clinical study.

          -  Additional criteria exist.