A Phase 1, Open-Label, Dose-Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of MGCD0103 (MG-0103) in Combination With Docetaxel (Taxotere®) in Subjects With Advanced Solid Malignancies
This Phase 1 study will evaluate escalating doses of orally administered MGCD0103 in
combination with two fixed doses (60 mg/m2 and 75 mg/m2) of IV docetaxel. In the US,
docetaxel is recommended at these or even higher doses (up to 100 mg/m2), both as a single
agent or in combination with other cytotoxic drugs (e.g., cisplatin, doxorubicin,
cyclophosphamide, and 5-fluorouracil), for the treatment of NSCLC, prostate cancer, gastric
adenocarcinoma, and head and neck cancer. In Japan, 60 mg/m2 IV docetaxel is the approved
dose for the treatment of breast cancer.
MGCD0103 belongs to the class of more selective, less globally cytotoxic agents being
investigated for treatment of cancers today, and may offer a lesser and/or non-overlapping
toxicity profile than the cytotoxic agents with which docetaxel is currently combined.
MGCD0103 doses ranging from 50 to 135 mg have been administered in combination with the
approved regimen of azacitidine (Vidaza®) (75 mg/m2/day for 5 days every 4 weeks) to
patients with high-risk MDS and AML. A 50 mg dose of MGCD0103 has been administered in
combination with the approved regimen of gemcitabine (1000 mg/m2 once weekly for 3
consecutive weeks of each 4-week cycle) to patients with advanced solid tumors; higher doses
of MGCD0103 will soon be evaluated in that trial.
Given the above, the proposed starting dose of 60 mg/m2 IV docetaxel and 50 mg MGCD0103 is
considered appropriately safe for initial investigation of this combination. Based on the
results observed in Part 1, the study may also evaluate 75 mg/m2 IV docetaxel and escalating
doses of orally administered MGCD0103 in Part 2 in order to determine whether this dosing
regimen is safe and would also warrant further investigation.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), and safety profile of escalating doses of orally administered MGCD0103 in combination with two fixed doses (60 mg/m2 and 75 mg/m2) of IV docetaxel.
Gregory Reid, MSc, MBA
United States: Food and Drug Administration
103 PH US 2007 CL001
|University of Pennsylvania||Philadelphia, Pennsylvania 19104|
|Johns Hopkins, Sidney Kimmel Comprehensive Cancer Center||Baltimore, Maryland 21231|