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Study Summary
No. 2007-0916:.......Advanced Cancers; Solid Tumors......Jennifer J. Wheler......Investigational Cancer Therapeutics
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Study Summary Title
Study Summary
Number:
2007-0916
Study Title:Open-Label Dose-Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Daily Oral MGCD265 Administered With Interruption to Subjects with Advanced Malignancies
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Physician New Patient Referral
Name:Jennifer J. WhelerPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Investigational Cancer TherapeuticsReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-563-1930
Contact us about clinical trials
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General Information
Disease Group:Advanced Cancers
Solid Tumors
Supported By:MethylGene, Inc.
Phase of Study:Phase IReturn
Visit:
Screening; Cycle 1, Days 1, 2, 3, 8, 15 and 21; Cycle 2, Days 1, and 8; Cycle 3
and beyond, Day 1; End of Treatment; Follow-up visit.
Treatment
Agents:
MGCD265Home Care:N/A
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of MGCD265 that can be given to patients with advanced cancer. The safety of
this drug will also be studied. There have been about 75 cancer patients that
have been treated to date with MGCD265.
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Study Objectives / Outcomes
This study is designed to evaluate the safety, pharmacokinetics (PK), pharmacodynamics
(PD), and antitumor activity of increasing dose levels of oral MGCD265 administered with
interruption to subjects with advanced malignancies.

Primary Objectives:
• To determine the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), and safety profile of oral MGCD265 administered with interruption to subjects with advanced malignancies.

Secondary Objectives:
• To evaluate the pharmacokinetic (PK) profile of MGCD265 (and possibly its metabolites);
• To evaluate the pharmacodynamic (PD) effects and potential biomarkers of MGCD265; and
• To evaluate antitumor activity (tumor response) of MGCD265.
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Study Status Information
Study Activation / Registration Date:01/24/2008
IRB Review and Approval Date:05/01/2008
Study Type:Phase I
Recruitment Status:Closed
Projected Accrual:60
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Patients with advanced metastatic or unresectable malignancy that is refractory to standard therapy and/or existing therapies are not likely to achieve clinical benefit. The patient's disease must be histologically confirmed.

2) Evaluable disease, but may be either measurable or non-measurable by RECIST criteria.

3) Last dose of prior chemotherapy, radiation therapy, or investigational agents occurred at least 4 weeks before the start of therapy on Cycle 1 Day 1.

4) Recovery from the adverse effects of prior therapy at the time of enrollment to </= grade 1 (excluding alopecia).

5) Age >/= 18 years.

6) Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

7) Life expectancy greater than 3 months following study entry.

8) Adequate renal function, defined as serum creatinine </= 1.5 x upper limit of normal (ULN), or creatinine clearance >/= 50 cc/min.

9) Adequate hepatic parameters, defined as aspartate aminotransferase (AST) [also serum glutamic oxaloacetic transaminase (SGOT)] and alanine aminotransferase (ALT) [also serum glutamic pyruvate transaminase (SGPT)] levels </= 2.5 x ULN, total bilirubin </= 1.5 x ULN, and alkaline phosphatase levels </= 2.5 x ULN. In the presence of liver metastases, adequate hepatic parameters are defined as ALT and AST </= 5 x ULN. In the presence of extensive bone metastases, alkaline phosphatase is defined as </= 5 x ULN.

10) Adequate bone marrow function, defined as an absolute neutrophil count (ANC) of >/= 1,500/mm^3 (>/= 1.5 x 10^9/L), a platelet count of >/= 100,000/mm^3 (>/= 100 x 10^9/L), and hemoglobin of >/= 9 gm/dL, in the absence of tranfusions.

11) A negative serum pregnancy test at screening for women of childbearing potential (WOCBP).

12) Agreement by WOCBP or men whose sexual partners are WOCBP to use two methods of adequate contraception (e.g., hormonal and barrier method) prior to study entry and for the duration of the study. WOCBP and men whose sexual partners are WOCBP must continue to use two methods of contraception for 28 days and 90 days, respectively, after the last dose of study medication.

13) Ability to understand and willingness to sign a written informed consent document.

14) Willingness and ability to comply with study visits and activities to be performed only at the study center.

15) For the Expanded MTD Cohort, the subject must have tumors that are accessible to biopsy and agree to undergo pretreatment and on study tumor biopsies.

Exclusion Criteria:1) Subjects with uncontrolled concurrent illness, including but not limited to: ongoing or active infection; history of recent hemoptysis; arterial hypertension (> 140/90 mm of mercury on medications); uncontrolled endocrine diseases; altered mental status or psychiatric illness/social situations that would limit compliance with study requirements and/or obscure study results.

2) Subjects with a history of a cardiovascular illness including but not confined to:congestive heart failure (New York Heart Association grade III or IV); angina pectoris or myocardial infarction within the previous year; or any clinically significant cardiac arrhythmia.

3) Subjects with QTc > 470 msec (including subjects on medication).

4) Subjects with left ventricular ejection fraction (LVEF) < 50%.

5) Subjects with leukemias or myelodysplastic syndrome.

6) Immunocompromised subjects, including subjects known to be infected with human immunodeficiency virus (testing is not required if there is no suspicion of the condition).

7) Subjects with a history of autologous bone marrow transplant (BMT) within the previous five years, or subjects with organ transplants or allogeneic BMT.

8) Subjects with lung tumor lesions with increased likelihood of bleeding, including: history of hemoptysis; evidence of cavitation; and invasion of aorta or pulmonary arteries by the tumor.

9) Subjects with a history of brain metastasis or leptomeningeal disease; subjects with tumors likely to metastasize to the brain should have a scan performed within 2 months of start of study to rule out brain metastasis (for example breast, lung, melanoma, sarcoma, etc.).

10) Subjects unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of oral drugs (e.g., watery diarrhea, hypokalemia, and achlorhydria (WDHA) syndrome, carcinoid syndromes, diarrhea due to infections, malabsorption syndromes secondary to surgery, or chemotherapy).

11) Subjects with a history of major surgery within 28 days of first receipt of study drug.

12) Nursing or pregnant women.

13) Subjects with any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the opinion of the Investigator, contraindicates the use of MGCD265 Drug Product or that may render the subject at excessively high risk for treatment complications.

14) Subjects with a known hypersensitivity to any of the components of the MGCD265 Drug Product (inactive ingredients: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, lutrol micro, and stearic acid).

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Links
Registration Number: NCT00679133
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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