A Phase I Study of MGCD0103 Given as a Three-Times Weekly Oral Dose in Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma
- Patients must have histologically or cytologically documented advanced or metastatic
solid malignancy or aggressive NHL with no reasonable likelihood of achieving
clinical benefit with existing therapies, that has failed to respond to standard
therapy, has progressed despite standard therapy, or for which no standard therapy
exists. Aggressive forms of NHL eligible for the study are:
- Burkitt's lymphoma
- Mantle cell lymphoma
- Diffuse large B-cell lymphoma
- Follicle-center cell lymphoma, large cell
- Primary mediastinal large B-cell lymphoma
- Patients with known central nervous system (CNS) metastases may be enrolled if they
have received radiotherapy for their CNS disease, if they have been on a stable dose
of steroids for at least 1 month prior to study entry, if they have had computed
tomography (CT) or magnetic resonance imaging (MRI) of the brain within 1 month of
study entry that shows stable disease and if they are free of neurological symptoms.
- Prior therapies allowed:
- Cytotoxic therapy
- Hormonal therapy/other therapy
- Luteinizing hormone releasing hormone (LHRH) agonist therapy
- Adjuvant therapy - Patients may have had unlimited prior adjuvant therapy. A
minimum of 28 days must have passed since the end of last treatment and study
initiation. Patients must have recovered from any treatment-related toxicities.
- ECOG performance status of 0, 1, or 2.
- Age ≥ 18 years.
- Minimum life expectancy of at least 3 months.
- Laboratory requirements
- Patients with a history of another cancer other than basal cell carcinoma or cervical
intraepithelial neoplasia (CIN/cervical in situ) unless the previous cancer was
treated and the patient has remained disease free for five years or more prior to the
current cancer diagnosis. Investigators desiring to enter patients with a second
malignancy must discuss with and obtain written approval in advance from the
MethylGene Medical Monitor.
- Pregnant or lactating women. Women of child-bearing potential must have a negative
serum pregnancy test documented within 7 days prior to registration on study.
- Patients and their partners, if either are of child-bearing potential, not using
adequate birth control measures throughout the course of the study. Both men and
women enrolled on study must agree to use a medically acceptable effective form of
contraception during the study and for 90 days following the last dose of study
medication. An effective form of contraception is an oral contraceptive or a double
barrier method, such as condom with diaphragm.
- Patients with known meningeal metastasis(es)
- Patients with active or uncontrolled infections, or with a fever > 38.5 degrees
Celsius on the day of scheduled dosing
- Patients with serious illnesses, medical conditions, or other medical history,
including laboratory results, which, in the investigator's opinion, would be likely
to interfere with a patient's participation in the study, or with the interpretation
of the results
- Patients who have been treated with any investigational drug within 30 days prior to
study initiation (an investigational drug is one for which there is no approved
indication), or who are receiving concurrent treatment with other experimental drugs
or anti-cancer therapy
- Known hypersensitivity to histone deacetylase (HDAC) inhibitors or any of the
components of MGCD0103
- Known HIV or hepatitis B or C (active, prior treated, or both).
- Any condition (e.g., known or suspected poor compliance, psychological instability,
geographical location, etc) that, in the judgment of the investigator, may affect the
patient's ability to sign the informed consent and undergo study procedures.