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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01849874




Registration number
NCT01849874
Ethics application status
Date submitted
6/05/2013
Date registered
9/05/2013

Titles & IDs
Public title
A Study of MEK162 vs. Physician's Choice Chemotherapy in Patients With Low-grade Serous Ovarian, Fallopian Tube or Peritoneal 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
Secondary ID [1] 0 0
C4211003
Secondary ID [2] 0 0
ARRAY-162-311
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Low-grade Serous Ovarian Cancer 0 0
Low-grade Serous Fallopian Tube Cancer 0 0
Low-grade Serous Peritoneal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MEK162, MEK inhibitor; oral
Treatment: Drugs - Physician's choice chemotherapy

Experimental: MEK162 -

Active comparator: Physician's choice chemotherapy -


Treatment: Drugs: MEK162, MEK inhibitor; oral
multiple dose, single schedule

Treatment: Drugs: 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)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
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)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From randomization date to the date of death, for censored participants at their last contact date (up to 24 months)
Secondary outcome [2] 0 0
Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST V1.1)
Timepoint [2] 0 0
From randomization until disease progression or death (up to 24 months)
Secondary outcome [3] 0 0
Duration of Response (DOR)
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Disease Control Rate (DCR)
Timepoint [4] 0 0
Week 24
Secondary outcome [5] 0 0
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [5] 0 0
From the first dose of study intervention until 30 days after the last dose (up to 9 years)
Secondary outcome [6] 0 0
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 4.03
Timepoint [6] 0 0
From the first dose of study intervention until 30 days after the last dose (up to 9 years)
Secondary outcome [7] 0 0
Quality of Life Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30)
Timepoint [7] 0 0
Screening, every 8 weeks from randomization for the first 72 weeks (while on treatment), treatment discontinuation visit, 30-day safety follow-up visit
Secondary outcome [8] 0 0
Quality of Life Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Ovarian Cancer Module (QLQ-OV28)
Timepoint [8] 0 0
Screening, every 8 weeks from randomization for the first 72 weeks (while on treatment), treatment discontinuation visit, 30-day safety follow-up visit
Secondary outcome [9] 0 0
Quality of Life Per Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-NTX)
Timepoint [9] 0 0
Screening, every 8 weeks from randomization for the first 72 weeks (while on treatment), treatment discontinuation visit, 30-day safety follow-up visit
Secondary outcome [10] 0 0
Predose Plasma Concentration (Ctrough) of MEK162
Timepoint [10] 0 0
Predose on Study Days 1, 57, and 113.
Secondary outcome [11] 0 0
Maximum Observed Plasma Concentration (Cmax) of MEK162
Timepoint [11] 0 0
2 hours ± 10 minutes postdose on Study Days 1, 57, and 113.

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/06/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/08/2022
Sample size
Target
Accrual to date
Final
341
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Dr Anil Arora - Wahroonga
Recruitment hospital [2] 0 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Mater Misericordiae Health Services Brisbane Limited - South Brisbane
Recruitment hospital [5] 0 0
Adelaide Cardiology - Adelaide
Recruitment hospital [6] 0 0
Adelaide Eye and Retina Centre - Adelaide
Recruitment hospital [7] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [8] 0 0
Thomas and Delaney Optometrists - Norwood
Recruitment hospital [9] 0 0
Burnside War Memorial Hospital - Toorak Gardens
Recruitment hospital [10] 0 0
Sunshine Hospital - St Albans
Recruitment hospital [11] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2076 - Wahroonga
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
5067 - Norwood
Recruitment postcode(s) [6] 0 0
5065 - Toorak Gardens
Recruitment postcode(s) [7] 0 0
3021 - St Albans
Recruitment postcode(s) [8] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
State/province [2] 0 0
California
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United States of America
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Colorado
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United States of America
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Connecticut
Country [5] 0 0
United States of America
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Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
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Illinois
Country [8] 0 0
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Indiana
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Iowa
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Maryland
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Massachusetts
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Michigan
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Missouri
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Montana
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New Mexico
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New York
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Ohio
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Oklahoma
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Pennsylvania
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Texas
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Virginia
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Austria
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Tirol
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Belgium
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Luxembourg
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Belgium
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Vlaams-brabant
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Belgium
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Brussels
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Belgium
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Gent
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Liege
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Belgium
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Namur
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Belgium
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Wilrijk
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
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Ontario
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Canada
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Quebec
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Czechia
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Hradec Kralove
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Olomouc
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Ostrava - Poruba
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Czechia
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Ostrava-Poruba
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Prague 2
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Czechia
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Prague
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North Jutland
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Herlev
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Kobenhavn o
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København Ø
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Tampere
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Besancon
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Lille
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LYON Cedex 08
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France
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Lyon
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Marseille Cedex 09
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France
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Marseille
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Montferrier S/lez
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Montpellier CEDEX 5
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France
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NANTES Cedex 2
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France
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Nantes
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France
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France
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Paris
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France
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Plerin
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France
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Saint-Herblain Cedex
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France
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Villejuif Cedex
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Germany
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Baden-wuerttemberg
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Germany
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Baden-wurttemberg
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Germany
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Bavaria
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Hessen
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North Rhine-westphalia
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Germany
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North-rhine Westphalia
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Germany
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Saxony
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Germany
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Schleswig-holstein
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Germany
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Berlin
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Freiburg
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Greifswald
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Heidelberg
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Gyor-moson-sopron
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Budapest
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Dublin 8
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Milano
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Pordenone
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Ravenna
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RM
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Rome
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Bologna
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Brescia
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Italy
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Catania
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Italy
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Napoli
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Italy
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Roma
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Netherlands
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Noord-holland
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Netherlands
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Groningen
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Netherlands
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Maastricht
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Norway
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Oslo
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Poland
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Warsaw
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Spain
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Barcelona
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Spain
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Castilla LA Mancha
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Spain
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Guipuzcoa
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Spain
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Cordoba
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Spain
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L'Hospitalet de Llobregat
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Spain
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Madrid
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Spain
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Palma de Mallorca
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Spain
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Sevilla
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Spain
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Toledo
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Spain
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Valencia
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Sweden
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Stockholm
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Sweden
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Uppsala
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United Kingdom
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England
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United Kingdom
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Nottinghamshire
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United Kingdom
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Surrey
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United Kingdom
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Sutton
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United Kingdom
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WEST Midlands
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United Kingdom
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London
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United Kingdom
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Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01849874