A Phase I Trial of Single Agent Trametinib (GSK1120212) in Advanced Cancer Patients With Hepatic Dysfunction
Jacksonville, Fla., Rochester, Minn.
Trial status: Open for Enrollment
Why is this study being done?
Patients will be separated into the following groups: Group A: Normal hepatic function, Group B: Mild hepatic dysfunction, Group C: Moderate hepatic dysfunction, Group D: Severe hepatic dysfunction
Groups of 3-6 patients to take part in each group will receive increasing doses of the study drug to until the best dose of study drug for each hepatic function group is found.
Trametinib is an oral drug that works by blocking mitogen-activated extracellular signal regulated kinase (MEK) 1 and MEK 2. MEK1 and MEK2 are important proteins that are needed for the growth of cells. When these proteins are blocked, it is believed that the growth of cancer cells will stop and the cancer cells will then die.
Who is eligible to participate?
- Histologically or cytologically confirmed solid malignancy that is metastatic or unresectable for which standard curative or palliative treatments do not exist or are no longer effective. Excludes: Pancreatic cancer patients, colorectal cancer patients, or BRAF V600E melanoma patients who have failed BRAF inhibitors
- Must have completed any prior treatments 28 days or more before study entry.
- 18 years of age or older.
- ECOG performance status 2 or less.
- Life expectancy of greater than 3 months.
- Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption.
- All prior treatment-related toxicities must recovered to an acceptable grade at the time of enrollment.
- Must have normal organ (except liver function) and marrow function
- Patients with abnormal hepatic function will be eligible.
- Women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to randomization. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, during the study participation, and for four months after the last dose of the drug.
- Ability to understand and the willingness to sign a written informed consent document.
- History of another malignancy.
- History of interstitial lung disease or pneumonitis.
- Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to enrollment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to enrollment.
- 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 and during the study. Patients previously treated with RAF and/or MEK inhibitors are excluded from the study.
- Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression.
- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib or excipients or to dimethyl sulfoxide (DMSO).
- Current use of a prohibited medication. The following medications or non-drug therapies are prohibited:
- Other anti-cancer therapy.
- Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy. Prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis.
- Herbal supplements
- History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
- History or evidence of cardiovascular risk
- Active Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible). Patients with known HIV infection are eligible if not on antiviral agents and CD4 counts are adequate (500 or greater).
- Uncontrolled intercurrent illness that would limit compliance with study requirements.
- Pregnant women or nursing mothers.
- HIV-positive patients on combination antiretroviral therapy.
- Any condition or medical problem in addition to the underlying malignancy and organ dysfunction which the investigator feels would pose unacceptable risk.