Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by EMD Serono
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT01936363
First received: August 23, 2013
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

This is a double blind, randomized, placebo-controlled, 2-arm, Phase 2 trial investigating the efficacy and safety of combination therapy of pimasertib plus SAR245409 and pimasertib placebo administered once per day compared to pimasertib administered twice per day plus SAR245409 placebo administered once per day in subjects with previously treated unresectable low-grade serous ovarian or peritoneal carcinoma or serous borderline ovarian or peritoneal tumors.


Condition Intervention Phase
Ovarian Cancer
Drug: Pimasertib once daily
Drug: Pimasertib placebo
Drug: SAR245409 placebo
Drug: SAR245409
Drug: Pimasertib twice daily
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase II Randomized Double Blind Placebo Controlled Trial of Combination of Pimasertib With SAR245409 or of Pimasertib With SAR245409 Placebo in Subjects With Previously Treated Unresectable Low Grade Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Objective tumor response defined as complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1) as determined by the investigator [ Time Frame: up to 2.5 years ] [ Designated as safety issue: No ]
    Objective tumor response will be measured from baseline until disease progression or death assessed every 8 weeks up to week 32, and thereafter every 12 weeks up to 2.5 years


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Time from randomization until first observation of progressive disease or death, when death occurs within 12 weeks of the last tumor assessment (whichever comes first), up to 30 days after last treatment ] [ Designated as safety issue: No ]
    Time from randomisation to the first documentation of objective disease progression according to RECIST v.1.1 as determined by the Investigator or death, whichever comes first. Death will be considered as a Progression-free survival (PFS) event only if it is reported within 12 weeks after the last tumor assessment without progression.

  • Percentage of subjects with disease control according to RECIST v.1.1 [ Time Frame: Baseline, Week 8, 16, 24 and 32, and thereafter every 12 weeks up to 30 days after last treatment ] [ Designated as safety issue: No ]
    Disease control defined as the proportion of subjects with stable disease (SD) for at least 16 weeks, PR or CR according to RECIST v.1.1

  • Overall survival time [ Time Frame: Time from randomization to death up to 12 months after last subject randomized ] [ Designated as safety issue: No ]
  • Health Related Quality of Life (HrQoL) assessed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) Version 3.0 [ Time Frame: Day 1 and Day 29, and Week 8, 16, 24 and 32, and thereafter every 12 weeks up to 30 days after last treatment ] [ Designated as safety issue: No ]
    The QLQ-C30 is a 30-item questionnaire comprising of five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea/vomiting), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact), and a global QoL scale summarized from two 7-point scales (overall QoL and overall general health)

  • HrQoL assessed using EORTC QLQ-C30 Version 3.0 - ovarian-specific module QLQ-OV28 [ Time Frame: Day 1 and Day 29, and Week 8, 16, 24 and 32, and thereafter every 12 weeks up to 30 days after last treatment ] [ Designated as safety issue: No ]
    The ovarian cancer module EORTC QLQ-OV28 assesses disease and treatment-related symptoms of ovarian cancer. The 28-item module comprises of 6 symptom scales (abdominal/gastrointestinal symptoms, peripheral neuropathy, other chemotherapy side-effects, hormonal symptoms, body image, attitude to disease and treatment), and sexual functioning. Both measures have been developed and validated in cross-cultural settings, exhibit good psychometric properties, and take between 10-15 minutes to complete

  • Number of Subjects with Treatment Emergent Adverse Events (TEAEs), Adverse Events (AEs) of special interest, Serious Adverse Events (SAEs), discontinuation of treatment due to TEAEs, death [ Time Frame: Baseline up to 30 days after last treatment ] [ Designated as safety issue: Yes ]
    TEAEs, SAEs and AEs will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0. An Adverse Event (AE) is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. Treatment-emergent adverse events are events from first dose of study drug that were absent before treatment or that worsened relative to pretreatment state.

  • Maximum Plasma Concentration (Cmax) After Dose of pimasertib and SAR245409 [ Time Frame: pre-dosing to 0.5, 1.5, 4.5 and 8 hours after the morning dose at day 15, 29, 43 ] [ Designated as safety issue: No ]
  • Area under the curve (AUC) After Dose of pimasertib and SAR245409 [ Time Frame: pre-dosing to 0.5, 1.5, 4.5 and 8 hours after the morning dose at day 15, 29, 43 ] [ Designated as safety issue: No ]
  • Molecular Alterations in MAPK and/or PI3K signaling pathway components/modulators in tumor tissue and blood [ Time Frame: Screening visit (day -28 to 1) ] [ Designated as safety issue: No ]

Estimated Enrollment: 110
Study Start Date: September 2013
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pimasertib (once daily) plus SAR245409 and Pimasertib placebo Drug: Pimasertib once daily
Pimasertib will be administered as oral capsule at a dose of 60 milligram (mg) once daily until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever comes first.
Drug: Pimasertib placebo
Placebo matching Pimasertib will be administered once daily in evening until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever comes first.
Drug: SAR245409
SAR245409 will be administered as oral capsule at a dose of 70 milligram (mg) once daily until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever comes first.
Experimental: Pimasertib (twice daily) plus SAR245409 placebo Drug: SAR245409 placebo
Placebo matching SAR245409 will be administered once daily in morning until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever comes first.
Drug: Pimasertib twice daily
Pimasertib will be administered as oral capsule at a dose of 60 milligram (mg) twice daily until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever comes first.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The female subject has a diagnosis of one of the following: a) low-grade serous ovarian or peritoneal carcinoma, or grade 1 serous ovarian or peritoneal carcinoma or well-differentiated serous ovarian or peritoneal carcinoma or b) serous borderline ovarian or peritoneal tumor, ovarian or peritoneal tumor of low-malignant potential, ovarian or peritoneal atypical proliferative serous tumor that recurs as low grade serous carcinoma or has invasive peritoneal implants.
  • The subject had at least one prior line of systemic therapy and has a tumor, which is not amenable to potentially curative surgical resection.
  • The subject has measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
  • The subject is at least 18 years old.
  • The subject has read and understood the written informed consent form (ICF) and is willing and able to give informed consent, fully understands the requirements of the trial and is willing to comply with all trial visits and assessments, including completion of patient-reported measures. Consent must be given before any trial related activities.
  • Women of childbearing potential must have a negative serum pregnancy test at the screening visit.
  • Women of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for 2 weeks prior to screening, during and at least 3 months after the last dose of trial medication.
  • Other protocol defined inclusion criteria may apply.

Exclusion Criteria:

  • The subject has previously been treated with a PI3K inhibitor and taken off treatment due to treatment related AEs.
  • The subject has been previously treated with a Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor.
  • Any anti-cancer therapy or treatment incorporating chemotherapy, immunotherapy, hormonal therapy, or biologic therapy within 28 days of the start of trial treatment or within 5 times the half life of such treatment, whichever is shorter. Treatment with nitrosoureas or mitomycin C are exceptions to this for which a treatment interval of at least 6 weeks is required
  • The subject has not recovered from toxicity due to prior therapy to Baseline level or National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0) Grade 1 or less (except alopecia). Residual chemotherapy-induced neuropathy grade <= 2 is permitted.
  • The subject has poor organ and marrow function as defined in the protocol.
  • The subject has creatine phosphokinase (CPK) elevation NCI CTCAE grade >=2, and/or a previous history of myositis or rhabdomyolysis.
  • The subject has difficulty swallowing, malabsorption or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the trial drug. Subjects requiring total parenteral nutrition are to be excluded.
  • The subject has a history of delayed healing/open wounds or diabetic ulcers.
  • The subject has a history of congestive heart failure, unstable angina, myocardial infarction, cardiac conduction abnormalities including Fridericia corrected QT interval (QTcF) prolongation of > 480ms or a pacemaker, clinically relevant impaired cardiovascular function (New York Heart Association (NYHA) class III/IV) or stroke within 3 months prior to enrollment.
  • The subject has a history of retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), uveitis or retinal vein occlusion (RVO), or has other relevant abnormalities identified on screening opthalmologic examination, which may increase the risk of serous retinal detachment (SRD) or RVO.
  • The subject has a history of uncontrolled intercurrent illness including but not limited to an active infection, hypertension, or uncontrolled diabetes (e.g. glycosylated hemoglobin >= 8%) that would limit compliance with treatment requirements.
  • Any previous malignancy treated with curative intent and the subject has been disease free for less than 5 years prior to randomization, with exception of Carcinoma‐in‐situ of the cervix, Squamous carcinoma of the skin, Basal cell carcinoma of the skin.
  • Other protocol defined exclusion criteria may apply.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01936363

Contacts
Contact: US Medical Information 888-275-7376
Contact: Merck KGaA Communication Center +49-6151-72-5200 service@merckgroup.com

Locations
United States, Massachusetts
Please Contact U.S. Medical Information Located in Recruiting
Rockland, Massachusetts, United States
Contact: for US Recruiting Sites    888-275-7376      
Germany
Please contact the Merck KGaA Communication Center located in Recruiting
Darmstadt, Germany
Contact: for EU Recruiting Sites    +49-6151-72-5200    service@merckgroup.com   
Sponsors and Collaborators
EMD Serono
Sanofi
Investigators
Study Director: Medical Responsible Merck KGaA
  More Information

No publications provided

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01936363     History of Changes
Other Study ID Numbers: EMR 200066_012, 2013-000902-40
Study First Received: August 23, 2013
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Institutional Review Board
Canada: Health Canada
Canada: Institutional Review Board
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Ethics Committee
Italy: Ethics Committee
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Poland: Ethics Committee
Poland: The Central Register of Clinical Trials
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Comité Ético de Investigación Clínica

Keywords provided by EMD Serono:
Ovarian Cancer
Pimasertib
Placebo
SAR245409

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on July 23, 2014