A Study of MEK162 vs. Physician's Choice Chemotherapy in Patients With Low-grade Serous Ovarian, Fallopian Tube or Peritoneal Cancer
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|ClinicalTrials.gov Identifier: NCT01849874|
Recruitment Status : Completed
First Posted : May 9, 2013
Results First Posted : March 30, 2021
Last Update Posted : November 3, 2022
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|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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||341 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||The MILO Study (MEK Inhibitor in Low-grade Serous Ovarian Cancer): A Multinational, Randomized, Open-label Phase 3 Study of MEK162 vs. Physician's Choice Chemotherapy in Patients With Recurrent or Persistent Low-grade Serous Carcinomas of the Ovary, Fallopian Tube or Primary Peritoneum|
|Actual Study Start Date :||June 27, 2013|
|Actual Primary Completion Date :||January 20, 2016|
|Actual Study Completion Date :||August 23, 2022|
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:
- Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: From randomization until documented progressive disease (PD) or death, whichever occurred first, for censored participants at the date of last adequate tumor assessment (up to 24 months) ]PFS was defined as the time from randomization to the earliest documented disease progression date or death due to any cause whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including Baseline) and an absolute increase of greater than or equal to (>=) 5 millimeter (mm). Appearance of new lesions >=10 mm in diameter also constituted PD. If a participant did not have an event at the time of the analysis cutoff or at the start of any new therapy, PFS was censored at the date of last adequate tumor assessment.
- Overall Survival (OS) [ Time Frame: From randomization date to the date of death, for censored participants at their last contact date (up to 24 months) ]OS was defined as the time from randomization to death due to any cause. Participants who were alive at the data cutoff date were censored for overall survival at their last contact date.
- Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST V1.1) [ Time Frame: From randomization until disease progression or death (up to 24 months) ]ORR was defined as the percentage of participants achieving an overall best response of complete response (CR) or partial response (PR) (responders). CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<) 10 mm, PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the Baseline sum of diameters. Non-target lesions must be non-progressive disease.
- Duration of Response (DOR) [ Time Frame: From the first radiographic evidence of response to the first documentation of PD or death, for censored participants at their last radiological assessment (up to 24 months) ]DOR was defined as the time from first radiographic evidence of response to the earliest documented progression date or death due to any cause, and was calculated on responders only. Responders with no PD or death date or subsequent anticancer therapy by the data cutoff date, were censored for DOR at their last radiological assessment. Responders who received subsequent anticancer therapy prior to PD or death were censored at their last radiological assessment prior to initiation of subsequent anticancer therapy.
- Disease Control Rate [ Time Frame: Week 24 ]Disease control rate was defined as percentage of participants with disease control. Disease control was defined as a best response of CR or PR, or stable disease (SD) documented at Week 24 or later. CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm, and PR is defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the Baseline sum of diameters. Non-target lesions must be non-progressive disease. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters on study.
- Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From the first dose of study drug until 30 days after the last dose (up to 25 months) ]An AE was any untoward medical occurrence in a participant who received vaccine without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
- Number of Participants With Shift Greater Than or Equal to Grade 3 From Baseline in Laboratory Parameter Values Based on National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.3 [ Time Frame: From the first dose of study drug until 30 days after the last dose (up to 25 months) ]Number of participants with shifts from normal Baseline values (Grade 0) to abnormal post-baseline values (shift to greater than or equal to Grade 3) were reported as per NCI-CTCAE, V4.3 graded from Grade 1 to 5. Grade 1: Mild; asymptomatic/ mild symptoms; clinical/diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local/noninvasive intervention indicated. Grade 3: Severe/medically significant but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Shifts in lab parameter from Grade 0 to 3, Grade 0 to 4 and Grade 0 to Low 3 and 4 and Grade 0 to High 3 and 4 (for parameters total hemoglobin, lymphocytes, white blood cells, calcium, magnesium, potassium, and sodium) were reported.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||Female|
|Gender Based Eligibility:||Yes|
|Accepts Healthy Volunteers:||No|
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01849874
|Study Director:||Pfizer Pfizer CT.gov Call Center||Pfizer|
|Other Study ID Numbers:||
C4211003 ( Other Identifier: Alias Study Number )
2013-000277-72 ( EudraCT Number )
|First Posted:||May 9, 2013 Key Record Dates|
|Results First Posted:||March 30, 2021|
|Last Update Posted:||November 3, 2022|
|Last Verified:||November 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.|
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Genital Neoplasms, Female
Endocrine System Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fallopian Tube Diseases