Trametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer

Not Recruiting

Trial ID: NCT02101788


This phase II/III trial studies how well trametinib works and compares it to standard treatment with either letrozole, tamoxifen, paclitaxel, pegylated liposomal doxorubicin, or topotecan in treating patients with low-grade ovarian cancer or peritoneal cavity cancer that has come back (recurrent), become worse (progressive), or spread to other parts of the body. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether trametinib is more effective than standard therapy in treating patients with ovarian or peritoneal cavity cancer.

Official Title

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 or Peritoneal Cancer

Stanford Investigator(s)

Oliver Dorigo, M.D., Ph.D.
Oliver Dorigo, M.D., Ph.D.

Professor of Obstetrics and Gynecology (Oncology)

Amer Karam
Amer Karam

Clinical Professor, Obstetrics & Gynecology - Gynecologic Oncology

Jonathan S. Berek, MD, MMSc
Jonathan S. Berek, MD, MMSc

Laurie Kraus Lacob Professor


Inclusion Criteria:

   - Patients age greater than 18 with the following tumors are included in the study:

      - Patients initially diagnosed with low-grade serous ovarian or peritoneal
      carcinoma that recur as low-grade serous carcinoma (invasive micropapillary
      serous carcinoma or invasive grade I serous carcinomas as defined by GOG,
      Federation of Obstetricians and Gynecologists [FIGO], World Health Organization
      [WHO] or Silverberg)

      - Patients initially diagnosed with serous borderline ovarian or peritoneal
      carcinoma that recur as low-grade serous carcinoma (invasive micropapillary
      serous carcinoma or invasive grade I serous carcinomas as defined by GOG, FIGO
      WHO or Silverberg)

   - At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g.
   MAJOR: laparotomy, laparoscopy, thoracotomy, VATS [video assisted thorascopic
   surgery]); there is no restriction on MINOR procedures: (e.g. central venous catheter
   placement, ureteral stent placement or exchange, tumor core or fine-needle aspirate
   [FNA] biopsy)

   - Patients must have documented low-grade serous carcinoma; confirmation must occur by
   prospective pathology review prior to study entry; the prospective pathology review
   can be done on tissue from the recurrent carcinoma or from original diagnostic

   - All patients must have measurable disease as defined by Response Evaluation Criteria
   in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one target
   lesion that can be accurately measured in at least one dimension (longest diameter to
   be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT),
   magnetic resonance imaging (MRI), or caliper measurement by clinical exam; or >= 20 mm
   when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured
   by CT or MRI; all imaging studies must be performed within 28 days prior to

   - 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 the five choices in the "standard therapy"

      - Any hormonal therapy directed at the malignant tumor must be discontinued at
      least one week prior to registration

      - Any other prior therapy directed at the malignant tumor, including chemotherapy
      and radiation therapy, must be discontinued at least 4 weeks prior to
      registration; any investigational agent must be discontinued at least 28 days
      prior to registration

   - Trametinib, can cause fetal harm when administered to a pregnant woman; women of
   child-bearing potential (i.e. patients whose reproductive organs remain in place and
   who have not passed menopause) and men must agree to use a highly effective method of
   contraception (e.g. hormonal, intrauterine device or; abstinence*) prior to study
   entry, during the study participation, and for six months after the last dose of the
   drug; women of child-bearing potential must have a negative serum pregnancy test
   within 14 days prior to randomization, cannot be breast-feeding, and must agree to use
   a highly effective form of contraception throughout the treatment period and for 6
   months after the last dose of study treatment; should a woman become pregnant or
   suspect she is pregnant while she or her partner is participating in this study, she
   should inform her treating physician immediately

      - Abstinence is only acceptable when this is in line with the preferred and usual
      lifestyle of the patient

   - Patients must have the ability to understand and sign an approved informed consent and
   authorization permitting release of personal health information

   - Patients must have a GOG performance status of 0 or 1

   - 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, bowel obstruction, or major resection of the stomach or

   - All prior treatment-related toxicities must be CTCAE v4 grade =< 1 (except alopecia)
   at the time of randomization

   - Patients must have a left ventricular ejection fraction >= lower limit of normal by
   echocardiogram (ECHO) or multigated acquisition scan (MUGA)

   - Serum creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault
   formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min (within 14
   days prior to treatment)

   - Bilirubin =< 1.5 times upper limit of normal (within 14 days prior to treatment)

   - Alanine aminotransferase (ALT) =< 2.5 times upper limit of normal (within 14 days
   prior to treatment)

   - Aspartate aminotransferase (AST) =< 2.5 times upper limit of normal (within 14 days
   prior to treatment)

   - Albumin >= 2.5 g/dL (within 14 days prior to treatment)

   - Prothrombin time (PT) and activated partial thromboplastin time (APTT) =< 1.5 times
   upper limit of normal (within 14 days prior to treatment)

   - Neutrophil count >= 1.5 x 10^9/L (within 14 days prior to treatment)

   - Platelet count >= 100 x 10^9/L (within 14 days prior to treatment)

   - Hemoglobin >= 9.0 g/dL (within 14 days prior to treatment)

   - If letrozole is selected as the control therapy, patients must be postmenopausal,
   either following bilateral oophorectomy or at least 5 years after 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 follicle stimulating hormone (FSH) levels; patients on hormone
   replacement therapy (HRT) must agree to withdrawal of hormone therapy before letrozole
   is started

Exclusion Criteria:

   - 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

   - Use of 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

   - If patients have had a potential index lesion radiated, it must have progressed post
   radiation therapy to be used as a measurable eligibility lesion

   - Patients may not have received prior MEK, v-Ki-ras2 Kirsten rat sarcoma viral oncogene
   homolog (KRAS), or v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor

   - 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

      - Because the composition, PK, and metabolism of many herbal supplements are
      unknown, 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 because of their poor prognosis and
   because they often develop progressive neurologic dysfunction that would confound the
   evaluation of neurologic and other adverse events

   - 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

      - Tumors for which no relapse has been observed within 5 years

   - Known hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with
   chronic or cleared HBV and HCV infection are eligible); patients with human
   immunodeficiency virus (HIV) are not eligible if on anti-retroviral medications

   - Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
   chemically related to trametinib, 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

      - 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
      randomization are eligible

      - History of (within 6 months prior to randomization) acute coronary syndromes
      (including myocardial infarction and unstable angina), coronary angioplasty, or

      - 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

      - Patients with intra-cardiac defibrillators or permanent pacemakers

      - Known cardiac metastases

   - Patients with a history or current evidence/risk of retinal vein occlusion (RVO)

   - Any serious and/or unstable pre-existing medical disorder (aside from malignancy
   exception above), psychiatric disorder, or other conditions that could interfere with
   subject's safety, obtaining informed consent or compliance to the study procedures

   - Patients who require use of a concomitant medication that can prolong the QT interval

   - Animal reproductive studies have not been conducted with trametinib; therefore, the
   study drug must not be administered to pregnant women or nursing mothers; women of
   childbearing potential should be advised to avoid pregnancy and use effective methods
   of contraception; if a female patient or a female partner of a patient becomes
   pregnant while the patient receives trametinib, the potential hazard to the fetus
   should be explained to the patient and partner (as applicable)


drug: Letrozole

drug: Tamoxifen Citrate

drug: Paclitaxel

drug: Pegylated Liposomal Doxorubicin Hydrochloride

other: Quality-of-Life Assessment

drug: Topotecan

drug: Trametinib Dimethyl Sulfoxide

other: Questionnaire Administration

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Charlene Fernandez

Stanford Cancer Center South Bay
2589 Samaritan Drive
San Jose, CA 95124
Charlene Fernandez

New Trial Alerts

Receive email alerts when trials open to patients.