A Study of MEK162 vs. Physician's Choice Chemotherapy in Patients With Low-grade Serous Ovarian, Fallopian Tube or Peritoneal Cancer

Study Description

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief 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.

Condition or disease	Intervention/treatment	Phase
Low-grade Serous Ovarian Cancer; Low-grade Serous Fallopian Tube Cancer; Low-grade Serous Peritoneal Cancer	Drug: MEK162, MEK inhibitor; oral; Drug: Physician's choice chemotherapy	Phase 3

Study Design

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	360 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Study Start Date :	June 2013
Actual Primary Completion Date :	April 1, 2016
Estimated Study Completion Date :	September 30, 2018

Arms and Interventions

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: MEK162	Drug: MEK162, MEK inhibitor; oral; multiple dose, single schedule
Active Comparator: Physician's choice chemotherapy	Drug: Physician's choice chemotherapy; 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)

Outcome Measures

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Demonstrate superior efficacy of study drug vs. physician's choice of selected chemotherapies in terms of increased progression-free survival. [ Time Frame: 3 years ]

Secondary Outcome Measures :

1. Obtain additional estimates of the efficacy of study drug vs. physician's choice of selected chemotherapies in terms of overall survival, objective response rate, duration of response and disease control rate. [ Time Frame: 6 years ]
2. Characterize the safety profile of the study drug vs. physician's choice of selected chemotherapies in terms of adverse events and clinical laboratory tests. [ Time Frame: 3 years ]
3. Assess the effect on global health status of study drug vs. physician's choice of selected chemotherapies in terms of quality-of-life questionnaires. [ Time Frame: 3 years ]
4. Characterize the plasma pharmacokinetics (PK) of study drug in terms of plasma concentration-time profiles and model-based PK parameters. [ Time Frame: 3 years ]

Eligibility Criteria

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 156 Study Locations

Sponsors and Collaborators

Array BioPharma

Investigators

Study Director:	Array BioPharma	303-381-6604

More Information

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Array BioPharma
ClinicalTrials.gov Identifier:	NCT01849874 History of Changes
Other Study ID Numbers:	ARRAY-162-311; 2013-000277-72 ( EudraCT Number )
First Posted:	May 9, 2013
Last Update Posted:	April 19, 2018
Last Verified:	April 2018

Additional relevant MeSH terms:

Fallopian Tube Neoplasms; Peritoneal Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases	Adnexal Diseases; Genital Diseases, Female; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases