Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer

NCT01936363 | Completed Phase 2 Results DMC

• 2 other identifiers: EMR 200066_0122013-000902-40
• Study Type: interventional
• Target: 65
• Locations: 7 countries
• Sites: 34

Brief Summary

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 participants with previously treated unresectable low-grade serous ovarian or peritoneal carcinoma or serous borderline ovarian or peritoneal tumors.

Conditions

Ovarian Cancer

Keywords

Ovarian Cancer; Pimasertib; Placebo; SAR245409

Outcome Measures

Primary Outcomes (1)

• Objective Tumor Response

  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 more than (\<) 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.

  From randomization until disease progression or death assessed every 8 weeks up to week 32, and thereafter every 12 weeks up to 52 months

Secondary Outcomes (9)

• Progression-Free Survival

  Time from randomization until first observation of progressive disease or death, assessed up to 52 months

• Percentage of Participants With Disease Control

  Randomization until disease progression or death assessed every 8 weeks up to week 32, and thereafter every 12 weeks up to 52 months

• Overall Survival

  Time from randomization until death, assessed up to 52 months

• Health Related Quality of Life (HrQoL) Assessed Using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30)

  Baseline up to disease progression or withdrawal, assessed up to 52 months

• 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)

  Baseline up to disease progression or withdrawal, assessed up to 52 months

Study Arms (2)

Pimasertib (once daily) plus SAR245409

EXPERIMENTAL

Drug: Pimasertib once daily; Drug: Pimasertib placebo; Drug: SAR245409

Pimasertib (twice daily) plus SAR245409 placebo

EXPERIMENTAL

Drug: SAR245409 placebo; Drug: Pimasertib twice daily

Interventions

Pimasertib once daily DRUG

Pimasertib 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 came first.

Pimasertib (once daily) plus SAR245409

Pimasertib placebo DRUG

Placebo matching Pimasertib administered once daily in evening until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.

Pimasertib (once daily) plus SAR245409

SAR245409 placebo DRUG

Placebo matching SAR245409 administered once daily in morning until disease progression, death, intolerable toxicity or withdrawal of informed consent, whichever came first.

Pimasertib (twice daily) plus SAR245409 placebo

SAR245409 DRUG

SAR245409 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 came first.

Pimasertib (once daily) plus SAR245409

Pimasertib twice daily DRUG

Pimasertib 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 came first.

Pimasertib (twice daily) plus SAR245409 placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The female participant had 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 participant had at least one prior line of systemic therapy and had a tumor, which was not amenable to potentially curative surgical resection
• The participant had measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• The participant had read and understood the written informed consent form (ICF) and was willing and able to gave informed consent, fully understood the requirements of the trial and was 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 had 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

You may not qualify if:

• The participant had previously been treated with a PI3K inhibitor and taken off treatment due to treatment related AEs
• The participant had 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 was shorter. Treatment with nitrosoureas or mitomycin C were exceptions to this for which a treatment interval of at least 6 weeks was required
• The participant had 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 was permitted
• The participant had poor organ and marrow function as defined in the protocol
• The participant had creatine phosphokinase (CPK) elevation NCI CTCAE grade greater than equal to (\>=) 2, and/or a previous history of myositis or rhabdomyolysis
• The participant had difficulty swallowing, malabsorption or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the trial drug. Participants requiring total parenteral nutrition were to be excluded
• The participant had a history of delayed healing/open wounds or diabetic ulcers
• The participant had 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 participant had a history of retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), uveitis or retinal vein occlusion (RVO), or had other relevant abnormalities identified on screening ophthalmologic examination, which might increase the risk of serous retinal detachment (SRD) or RVO
• The participant had 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 participant had 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

Sponsors & Collaborators

• EMD Serono: lead
• Sanofi: collaborator

Study Sites (34)

Research site

Augusta, Georgia, 30912, United States

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Chicago, Illinois, 60637, United States

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Indianapolis, Indiana, 46202, United States

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Silver Spring, Maryland, 20910, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02215-5450, United States

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Ann Arbor, Michigan, 48109, United States

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Detroit, Michigan, 48202, United States

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Kansas City, Missouri, 64111, United States

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St Louis, Missouri, 63110, United States

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Kalispell, Montana, 59901, United States

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New York, New York, 10065, United States

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Cincinnati, Ohio, 45219, United States

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Columbus, Ohio, 43210, United States

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Middletown, Ohio, 45042, United States

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Nashville, Tennessee, 37203, United States

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Houston, Texas, 77030, United States

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Northmead, New South Wales, 2152, Australia

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Greenslopes, Queensland, 4120, Australia

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Subiaco, Western Australia, 6008, Australia

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Kortrijk, 8500, Belgium

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Leuven, 3000, Belgium

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Hamilton, Ontario, L8V 5C2, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Montreal, Quebec, H2L 4M1, Canada

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Montreal, Quebec, H2W 1S6, Canada

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Québec, G1R 2J6, Canada

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Bordeaux, Gironde, 33076, France

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Chorzów, 41-500, Poland

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Palma Mallorca, Balearic Islands, 07198, Spain

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Madrid, 28033, Spain

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Madrid, 28046, Spain

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Seville, 41013, Spain

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Valencia, 46010, Spain

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MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

XL765

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2013
• First Posted: September 6, 2013
• Study Start: September 30, 2013
• Primary Completion: May 31, 2015
• Study Completion: November 30, 2017
• Last Updated: December 12, 2018
• Results First Posted: April 7, 2017

Record last verified: 2018-11

Locations

ES (5); PL (1); BE (2); AU (3); FR (1); US (17); CA (5)