A Phase I/II Study of MGCD0103 (MG-0103) in Combination With Gemcitabine

This study has been completed.
Sponsor:
Information provided by:
MethylGene Inc.
ClinicalTrials.gov Identifier:
NCT00372437
First received: September 5, 2006
Last updated: October 23, 2013
Last verified: October 2013
  Purpose

Inthis study, MGCD0103, a new anticancer drug under investigation, is given three times weekly in combination with gemcitabine to patients with solid tumours.


Condition Intervention Phase
Tumors
Drug: MGCD0103
Drug: Gemcitabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of MGCD0103 (MG-0103) in Combination With Gemcitabine

Resource links provided by NLM:


Further study details as provided by MethylGene Inc.:

Primary Outcome Measures:
  • Maximum tolerated dose in combination with azacitidine [ Time Frame: 1 year (anticipated) ] [ Designated as safety issue: Yes ]
  • Response rate [ Time Frame: 1 year (anticipated) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response. [ Time Frame: 1 year (anticipated) ] [ Designated as safety issue: No ]
  • Pharmacodynamics (histone acetylation, biomarkers) [ Time Frame: 1 year (anticipated) ] [ Designated as safety issue: No ]

Enrollment: 47
Study Start Date: September 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: MGCD0103
MGCD0103 as an oral dose three times per week.
Drug: Gemcitabine
Gemcitabine 1000mg/m<2> intravenously days 1, 8, 15 of a 28 day cycle.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically documented cancer: Phase I--solid tumors where gemcitabine is considered standard of care; refractory solid tumor 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. Phase II--locally advanced and measurable (non-resectable III) or metastatic (Stage IV) pancreatic cancer.
  • Patients with known CNS metastases may be enrolled on Phase I or II only if they meet the following criteria:

    • They have received radiotherapy for their CNS disease;
    • They have had steroids discontinued for at least 1 month prior to study entry;
    • They have had a CT or MRI of the brain within 1 month of study entry that shows stable disease; and d)they are free of neurological symptoms.
  • Karnofsky performance status of 70 or greater.
  • Age 18 years and over.
  • Laboratory requirements (must be done within 14 days prior to study initiation):

    • Hematology: White Blood Cells (WBC)≥3 x 10<9>/L (≥ 3000/mm3);
    • Absolute Neutrophil Count (ANC) ≥1.5 x 10<9>/L (≥1500/mm3);
    • Platelets ≥100 x 10<9>/L (≥100,000/mm3);
    • Chemistry: Total Bilirubin ≤1.5 x Upper Limit of Normal(ULN);
    • AST(SGOT)and ALT(SGPT)≤3 x ULN; ≤ 5 x ULN if documented liver metastases;
    • Serum Creatinine ≤1.5 x ULN or calculated creatinine clearance ≥50 mL/min;
    • Urinalysis: Proteinuria <1 mg/dl or 500 mg protein/24 hours if dipstick ≥2+.
  • Patients or their legal representative must be able to read (or have read to them), understand, and sign a written informed consent (approved by the institutional review board/Ethics Committee (IRB/EC)) within 14 days prior to start of treatment.

Exclusion Criteria:

  • Patients with another active cancer (excluding basal cell carcinoma or cervical intraepithelial neoplasia (CIN/cervical in situ or melanoma in situ). (Phase II portion only)
  • Pregnant or lactating women. Women of child bearing potential (WOCBP) must have a negative serum pregnancy test documented within 7 days prior to starting study drug.
  • WOCBP and men whose partners are WOCBP must use an acceptable method of contraception while enrolled on this study, and for a period of 3 months following study drug treatment. Patients unwilling or unable to follow this guideline will be excluded. Investigators should follow their Institutional standard regarding acceptable methods of contraception.
  • Patients with uncontrolled concomitant illness, active infection requiring i.v. antibiotics, or uncontrolled infections, or a fever >38.5C 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 28 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 HDAC inhibitors or to any of the components of MG-0103.
  • Known hypersensitivity to gemcitabine.
  • Prior treatment with gemcitabine (during the expanded phase II portion only).
  • Known HIV or known active Hepatitis B or C.
  • 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.
  • Any condition that will put the patient at undue risk or discomfort as a result of adherence to study procedures. For example, consider requirement to take MG-0103 with a low pH drink and recommendation to avoid agents that increase gastric pH.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00372437

Locations
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Kansas
Veterans Affairs Medical Center
Kansas City, Kansas, United States, 64128
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Gabrail Cancer Center
Canton, Ohio, United States, 44718
United States, Pennsylvania
Pennsylvania Presbyterian Medical Center
Philadelphia, Pennsylvania, United States, 19104-4283
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-6307
Canada, Quebec
McGill University/Dept Oncology
Montreal, Quebec, Canada, H2W 1S6
CHUS Hopital Fleurimont
Sherbrooke, Quebec, Canada, J1H 5N4
Sponsors and Collaborators
MethylGene Inc.
Investigators
Study Director: Gregory Reid, MSc, MBA MethylGene Inc.
  More Information

No publications provided

Responsible Party: Gregory Reid, Chief Medical Officer, MethylGene, Inc.
ClinicalTrials.gov Identifier: NCT00372437     History of Changes
Other Study ID Numbers: 0103-006
Study First Received: September 5, 2006
Last Updated: October 23, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by MethylGene Inc.:
Refractory solid tumors
Phase I/II
Refractory and solid tumors

Additional relevant MeSH terms:
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014