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Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT01936363
First received: August 23, 2013
Last updated: February 22, 2017
Last verified: February 2017
  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
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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 [ Time Frame: From randomization until disease progression or death assessed every 8 weeks up to week 32, and thereafter every 12 weeks up to Data Cut-off (19 May 2015) ]
    Objective tumor response was defined as the presence of at least one Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.


Secondary Outcome Measures:
  • Progression-Free Survival [ Time Frame: Time from randomization until first observation of progressive disease or death, assessed up to Data Cut-off (19 May 2015) ]
    PFS defined as time from randomization to first documentation of objective tumor progression.CR:Disappearance of all target lesions.Any pathological lymph nodes(whether target or non-target)must have reduction in short axis to<10 mm.PR:At least 30% decrease in sum of diameters of target lesions,taking as reference baseline sum diameters.PD:At least a 20% increase in sum of diameters of target lesions,taking as reference smallest sum on study.In addition to relative increase of 20%,the sum also demonstrate absolute increase of at least 5 mm.SD:Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD,taking as reference smallest sum diameters while on study. PFS calculated as(Months)=first event date minus randomization or first dose date plus 1.Median PFS was computed using Kaplan-Meier estimates (product-limit estimates) and was presented with 95% confidence interval.The confidence intervals for median was calculated according to Brookmeyer and Crowley.

  • Percentage of Subjects With Disease Control [ Time Frame: Randomization until disease progression or death assessed every 8 weeks up to week 32, and thereafter every 12 weeks up to Data Cut-off (19 May 2015) ]
    Disease control as per RECIST v.1.1 was defined as the proportion of subjects with stable disease (SD), for at least 16 weeks, PR or CR according to RECIST v1.1 criteria. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: At least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters). CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.

  • Overall Survival [ Time Frame: Time from randomization until death, assessed up to Data Cut-off (19 May 2015) ]
    Overall survival (OS) was defined as the time (in months) from randomization to death. Data has been presented in terms of number subjects who died and number of censored subjects.

  • Health Related Quality of Life (HrQoL) Assessed Using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) [ Time Frame: Baseline up to disease progression or withdrawal, assessed up to Data Cut-off (19 May 2015) ]
    EORTC 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 quality of life (QoL) scale summarized from two 7-point scales (overall QoL and overall general health). Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and the individual single-items ranged in score from 0 to 100. A high scale score represents a higher response level. High score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

  • Health Related Quality of Life (HrQoL) Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Ovarian-Specific Module Quality of Life Questionnaire Ovarian Cancer Module (QLQ-OV28) [ Time Frame: Baseline up to disease progression or withdrawal, assessed up to Data Cut-off (19 May 2015) ]
    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. All of the scales and the individual single-items ranged in score from 0 to 100. Higher scores indicate a better quality of life.

  • Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation of Treatment and Death [ Time Frame: First dose of study drug up to Data Cut-off (19 May 2015) ]
    TEAEs, SAEs and AEs was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0. An adverse events was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to data cut-off 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-dose Hour 0.5, 1.5, 4.5 8 post dose on Day 15, 29, 43 ]
  • Area Under the Curve (AUC) After Dose of Pimasertib and SAR245409 [ Time Frame: Pre-dose Hour 0.5, 1.5, 4.5 8 post dose on Day 15, 29, 43 ]
  • Molecular Alterations in MAPK and/or PI3K Signaling Pathway Components/Modulators in Tumor Tissue and Blood [ Time Frame: Screening visit (day -28 to 1) ]

Enrollment: 65
Study Start Date: September 2013
Estimated Study Completion Date: November 2017
Primary Completion Date: May 2015 (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   (Adult, Senior)
Sexes 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 less than equal to (<=) 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 greater than equal to (>=) 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 > 480 milliseconds (ms) 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 percent [%]) 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

  Show 61 Study Locations
Sponsors and Collaborators
EMD Serono
Sanofi
Investigators
Study Director: Medical Responsible Merck KGaA
  More Information

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01936363     History of Changes
Other Study ID Numbers: EMR 200066_012
2013-000902-40 ( EudraCT Number )
Study First Received: August 23, 2013
Results First Received: May 31, 2016
Last Updated: February 22, 2017

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
Niacinamide
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 17, 2017