OGS: A randomized phase II/III study to assess the efficacy of trametinib (GSK 1120212) in patients with recurrent or progressive low-grade serous ovarian cancer of peritoneal cancer (GOG-0281)
- Conditions
- Recurrent low grade serous ovarian or peritoneal cancerMedDRA version: 18.1Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-001627-39-GB
- Lead Sponsor
- HS Greater Glasgow and Clyde
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 250
-Patients age greater than 18 years of age.
- Patients initially diagnosed with low grade serous ovarian or peritoneal carcinoma that as recur as low grade serous carcinoma.
- Patients initially diagnosed with serous borderline ovarian or peritoneal carcinoma.
- Patients must have documented low grade serous carcinoma . Confirmation must occur by prospective pathology review prior to study entry.
- Patients must have measurable disease according Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
- Prior Therapy : Patients must have recurred or progressed following at least one platinum-based chemotherapy regimen
Patients may have received an unlimited number of prior therapy regimens.
Patients may not have received all of five choices in the standard therapy arm.
- An image guided core biopsy of fresh tissue must be obtained prior to randomisation and submitted for translational research purposes.
- Patients of childbearing potential must have a negative pregnancy test, cannot be breast feeding, and must agree to practice a highly effective means of birth control prior to study entry, for the duration of the study participation, and for six months after last dose of study treatment.
- Patient has given written informed consent
- Patient must have performance status of 0 or 1.
- Patient must be able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption,such as malabsorption syndrome or major resection of the stomach or bowels.
- Patients must have a left ventricular ejection fraction > = lower limit of normal by echocardiogram (ECHO) of multigated acquistion scan (MUGA).
- Patients must have adequate bone marrow function, renal function, endocrine and hepatic function as defined by study protocol.
- If letrozole is selected as the control therapy, patients must be menopausal, either following bilateral oophorectomy or least 5 years spontaneous menopause; patients within 5 years of spontaneous menopause or who have had a hysterectomy without bilateral oophorectomy must have postmenopausal luteinizing hormone (LH) and follical stimulating hormone (FSH) levels; patients on hormone replacement therapy must agree to withdrawal of hormone therapy before letrozole is started.
- All prior treatment-related toxicities must be CTCAE v4 grade <1 (except alopecia) at the time of randomization
- At least 4 weeks must have elapsed since the patient underwent any major surgery.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- If patients have received other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of trametinib or standard of care agent they will be excluded.
- If patients have had a potential index lesion radiated, it must have progressed post radiation therapy to be used a measurable eligibility lesion.
- Patients may not have received prior MEK, KRAS, or BRAF inhibitor therapy.
- Current use of a prohibited medication. The following medications or non-drug therapies are prohibited:
: Patients may not be receiving any other anti-cancer or investigational agents.
: The concurrent use of all herbal supplements is prohibited during the study (including, but not limited to St. John’s Wort, kava, ephedra [ma huang], gingko biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng).
- Patients with known leptomeningeal or brain metastases or spinal cord compression should be excluded from this clinical trial
- Patients with a bowel obstruction or any other gastrointestinal condition that might affect absorption of the oral drug should be excluded; this would include patients with inability to swallow and retain orally-administered medication, malabsorption syndrome, or those with a major resection of the stomach or bowels
- Patients with a history of interstitial lung disease or pneumonitis
- Patients with a previous or current malignancy at other sites should be excluded, with the exception of:
Curatively treated local tumors such as carcinoma-in-situ of the cervix, basal or squamous cell carcinoma of the skin.
Tumours for which no relapse has been observed within 5 years.
- Patients with active hepatitis B or C; human immunodeficiency virus (HIV) infected patients with adequate CD4 counts (> 350 cells/mm3) will be eligible; HIV-positive patients on combination antiretroviral therapy are ineligible
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug, or excipients, or to dimethyl sulfoxide (DMSO), or to Cremophor EL (polyoxyethylated castor oil); please note, exclusion for Cremophor is unnecessary unless paclitaxel is the only agent available and the patient randomizes to the conventional therapy option
- Patients with a history or evidence of cardiovascular risk, including any of the following:
:Left ventricular ejection fraction (LVEF) < lower limit of normal (LLN)
: Bazett's corrected QT (QTcB) >= 480 msec
: History or evidence of current clinically significant uncontrolled arrhythmias
: Exception: Subjects with controlled atrial fibrillation for > 30 days prior to randomisation are eligible
: History of (within 6 months prior to randomisation) acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting
:History or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA)
:Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy
:Patients with intra-cardiac defibrillators or permanent pacemakers
:Known cardiac metastases
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method