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Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01936363
First Posted: September 6, 2013
Last Update Posted: September 26, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Sanofi
Information provided by (Responsible Party):
EMD Serono
August 23, 2013
September 6, 2013
May 31, 2016
April 7, 2017
September 26, 2017
September 30, 2013
May 31, 2015   (Final data collection date for primary outcome measure)
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.
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 ]
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
Complete list of historical versions of study NCT01936363 on ClinicalTrials.gov Archive Site
  • 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) ]
  • 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 ]
    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 ]
    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 ]
  • 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 ]
    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 ]
    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 ]
    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 ]
  • 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 ]
  • Molecular Alterations in MAPK and/or PI3K Signaling Pathway Components/Modulators in Tumor Tissue and Blood [ Time Frame: Screening visit (day -28 to 1) ]
Not Provided
Not Provided
 
Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer
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
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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Ovarian Cancer
  • 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 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: 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.
  • 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.
  • Experimental: Pimasertib (once daily) plus SAR245409 and Pimasertib placebo
    Interventions:
    • Drug: Pimasertib once daily
    • Drug: Pimasertib placebo
    • Drug: SAR245409
  • Experimental: Pimasertib (twice daily) plus SAR245409 placebo
    Interventions:
    • Drug: SAR245409 placebo
    • Drug: Pimasertib twice daily
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
65
November 30, 2019
May 31, 2015   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: Female
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Belgium,   Canada,   France,   Poland,   Spain,   United States
Germany,   Italy
 
NCT01936363
EMR 200066_012
2013-000902-40 ( EudraCT Number )
Yes
Not Provided
Not Provided
EMD Serono
EMD Serono
Sanofi
Study Director: Medical Responsible Merck KGaA
EMD Serono
September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP