A clinical study evaluating the efficacy of an investigational compound (MEK162) in adult female patients with a specific type of ovarian, fallopian tube or peritoneum cancer

• Register: EUCTR
• Last refreshed on: 11 December 2017
• Main ID: EUCTR2013-000277-72-AT
• Date of registration: 14/08/2013
• Prospective Registration: Yes
• Primary sponsor: Array BioPharma Inc.
• Public title: A clinical study evaluating the efficacy of an investigational compound (MEK162) in adult female patients with a specific type of ovarian, fallopian tube or peritoneum cancer
• Scientific 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 - The MILO Study (MEK Inhibitor in Low-grade Serous Ovarian Cancer)
• Date of first enrolment: 18/02/2014
• Target sample size: 360
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000277-72
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Hungary, Ireland, Italy, Luxembourg, Netherlands, Norway, Poland, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Franklin Vairinhos
• Affiliation: Array BioPharma Inc.

• Name: Franklin Vairinhos
• Affiliation: Array BioPharma Inc.

Key inclusion & exclusion 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:
•History or current evidence of retinal vein occlusion (ROV), or current risk factors for ROV
•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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

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)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: MEK162
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BINIMETINIB
CAS Number: 606143-89-9
Current Sponsor code: MEK162
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Trade Name: Paclitaxel
Product Name: Paclitaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Trade Name: Potactasol
Product Name: Topotecan
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: TOPOTECAN
CAS Number: 123948-87-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Caelyx
Product Name: Liposomal doxorubicin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PEGYLATED LIPOSOMAL DOXORUBICIN
CAS Number: 23214-92-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

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 (dated 15 March 2017), BICR review of tumour assessments will no longer be performed; tumour assessments in both the randomized and crossover periods will be conducted by the study sites according to institutional standards. Results of tumour assessments will be retained in patient files only and no longer entered into the eCRFs. As of Protocol Version 6, all patients will return for a 30-Day 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.

Timepoint(s) of evaluation of this end point: Tumor assessments will be performed every 8 weeks from
randomization for the first 72 weeks, then every 12 weeks while the
patient is receiving study drug treatment, irrespective of the days of study drug administration. Patients who have locally
determined Progressive Disease (PD) confirmed by the BICR will discontinue study drug and cease tumor assessments. Patients who discontinue study drug for reasons other than PD per BICR will continue to have tumor assessments every 8 weeks from randomization for the first 72 weeks, then every 12 weeks for the remainder of the study until one of the following (whichever occurs first): locally determined PD is confirmed by the BICR, withdrawal of consent, initiation of subsequent anticancer therapy, lost to follow-up or death.

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
- Assess the effect on global health status of MEK162 vs. physician’s choice of selected chemotherapies
- Characterize the plasma PK of MEK162 in this patient population
- During the crossover period, after failure of physician´s choice chemotherapy in the randomized period :
- Assess the efficacy of MEK162
- Characterise the safety profile of MEK162
- Assess the effect on global health status of MEK162

Secondary Outcome(s)

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 study ends.
ORR, DOR, DCR: Tumor assessments will be performed every 8 weeks from randomization for the first 72 weeks, then every 12 weeks for the remainder of the study
Safety:Continuously while on study drug and for 30 days after the last dose of study drug.
Patient Reported Outcomes: The EORTC QLQ-C30, EORTC QLQ-OV28 and FACT-GOG/NTX questionnaires will be completed within 7 days prior to randomization; every 8 weeks from randomization for the first 72 weeks; at the Treatment Discontinuation Visit;and at the 30-Day Safety Follow-up Visit.
PK:Pharmacokinetic samples will be drawn predose and
2 hours ± 10 minutes postdose on Days 1, 57 and 113.

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

Secondary ID(s)

2013-000277-72-HU

ARRAY-162-311

NCT01849874

Source(s) of Monetary Support

Array BioPharma Inc.

Novartis Pharma AG