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Ovarian CancerPhase 2NCT01936363

Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer

A Phase 2 study testing Pimasertib once daily, SAR245409 and Pimasertib twice daily in people with Ovarian Cancer, run by EMD Serono at 34 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Ovarian Cancer
What is being tested?
Pimasertib once daily, SAR245409 and Pimasertib twice daily
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
65 participants
Where
34 sitesin 7 countries
Study dates
30 Sep 2013to 30 Nov 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • Other protocol defined inclusion criteria may apply

Who cannot join

  • 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
Show all 13Show fewer
  • 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
  • Other protocol defined exclusion criteria may apply

Trial locations and contacts

34 sites in 7 countries.

34 sites in 7 countries

United States17 sites

  • Research site

    Ann Arbor, Michigan, 48109

  • Research site

    Augusta, Georgia, 30912

  • Research site

    Boston, Massachusetts, 02114

  • Research site

    Boston, Massachusetts, 02215-5450

  • Research site

    Chicago, Illinois, 60637

  • Research site

    Cincinnati, Ohio, 45219

  • Research site

    Columbus, Ohio, 43210

  • Research site

    Detroit, Michigan, 48202

  • Research site

    Houston, Texas, 77030

  • Research site

    Indianapolis, Indiana, 46202

  • Research site

    Kalispell, Montana, 59901

  • Research site

    Kansas City, Missouri, 64111

  • Research site

    Middletown, Ohio, 45042

  • Research site

    Nashville, Tennessee, 37203

  • Research site

    New York, New York, 10065

  • Research site

    Silver Spring, Maryland, 20910

  • Research site

    St Louis, Missouri, 63110

Other trials in United States

Canada5 sites

  • Research site

    Hamilton, Ontario, L8V 5C2

  • Research site

    Montreal, Quebec, H2L 4M1

  • Research site

    Montreal, Quebec, H2W 1S6

  • Research site

    Québec, G1R 2J6

  • Research site

    Toronto, Ontario, M4N 3M5

Other trials in Canada

Spain5 sites

  • Research site

    Madrid, 28033

  • Research site

    Madrid, 28046

  • Research site

    Palma Mallorca, Balearic Islands, 07198

  • Research site

    Seville, 41013

  • Research site

    Valencia, 46010

Other trials in Spain

Australia3 sites

  • Research site

    Greenslopes, Queensland, 4120

  • Research site

    Northmead, New South Wales, 2152

  • Research site

    Subiaco, Western Australia, 6008

Other trials in Australia

Belgium2 sites

  • Research site

    Kortrijk, 8500

  • Research site

    Leuven, 3000

Other trials in Belgium

France1 site

  • Research site

    Bordeaux, Gironde, 33076

Other trials in France

Poland1 site

  • Research site

    Chorzów, 41-500

Other trials in Poland

About this study

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

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
Being tested
Pimasertib once daily, Pimasertib placebo, SAR245409 placebo, SAR245409, Pimasertib twice daily
Keywords
Ovarian Cancer, Pimasertib, Placebo, SAR245409
Medical subject headings
Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pimasertib once dailyDrug

    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 placeboDrug

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

  • SAR245409 placeboDrug

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

  • SAR245409Drug

    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 twice dailyDrug

    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.

Study groups in NCT01936363
Study groupRoleWhat they receive
Pimasertib (once daily) plus SAR245409ExperimentalNot described
Receives: Drug: Pimasertib once daily; Drug: Pimasertib placebo; Drug: SAR245409
Pimasertib (twice daily) plus SAR245409 placeboExperimentalNot described
Receives: Drug: SAR245409 placebo; Drug: Pimasertib twice daily

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Progression-Free Survival

    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.

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

  2. Percentage of Participants With Disease Control

    Disease control as per RECIST v.1.1 was defined as the proportion of participants 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.

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

  3. Overall Survival

    Overall survival (OS) was defined as the time (in months) from randomization to death. Data has been presented in terms of number participants who died and number of censored participants.

    Measured: Time from randomization until death, assessed up to 52 months

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

    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.

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

  5. 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)

    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.

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

  6. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Treatment and Death

    TEAEs, Serious TEAEs and AEs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0. An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A Serious Adverse Event 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.

    Measured: First dose of study drug up to 52 months

  7. Maximum Plasma Concentration (Cmax) After Dose of Pimasertib and SAR245409

    Measured: Pre-dose Hour 0.5, 1.5, 4.5 8 post dose on Day 15, 29, 43

  8. Area Under the Curve (AUC) After Dose of Pimasertib and SAR245409

    Measured: Pre-dose Hour 0.5, 1.5, 4.5 8 post dose on Day 15, 29, 43

  9. Molecular Alterations in MAPK and/or PI3K Signaling Pathway Components/Modulators in Tumor Tissue and Blood

    Measured: Screening visit (day -28 to 1)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Sep 2013 (estimated)
  2. Study start30 Sep 2013
  3. Primary completion31 May 2015
  4. Study completion30 Nov 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
65 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01936363
Sponsor's protocol ID
EMR 200066_012
Other IDs
2013-000902-40
Status last verified
Nov 2018
First submitted
23 Aug 2013
Last updated
12 Dec 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pimasertib once daily, SAR245409 and Pimasertib twice daily in people with Ovarian Cancer, run by EMD Serono at 34 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in United States, Canada, Spain, Australia, Belgium and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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 52 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01936363.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2018.

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