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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00372437
Recruitment Status : Completed
First Posted : September 7, 2006
Last Update Posted : July 1, 2015
Information provided by (Responsible Party):
Mirati Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE September 5, 2006
First Posted Date  ICMJE September 7, 2006
Last Update Posted Date July 1, 2015
Study Start Date  ICMJE September 2006
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2007)
  • Maximum tolerated dose in combination with azacitidine [ Time Frame: 1 year (anticipated) ]
  • Response rate [ Time Frame: 1 year (anticipated) ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 6, 2006)
  • Phase I: To determine the Maximum Tolerated Dose (MTD) and recommended Phase II dose of MG-0103 when administered in combination with gemcitabine (Gemzar) to patients with refractory solid tumors.
  • Phase II: To estimate the overall response rate of the combination of MG-0103 and gemcitabine (Gemzar) when administered to gemcitabine-naïve patients with locally advanced (non-resectable III) or metastatic (Stage IV) pancreatic cancer.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2007)
  • Objective response. [ Time Frame: 1 year (anticipated) ]
  • Pharmacodynamics (histone acetylation, biomarkers) [ Time Frame: 1 year (anticipated) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2006)
  • (Phase I): To describe the dose limiting toxicities of the combination of MG-0103 and gemcitabine.
  • (Phase I and II): To describe objective responses to MG-0103 and gemcitabine.
  • (Phase I and II): To measure the pharmacodynamic (PD) effects on changes in histone acetylation and expression of certain genes related to downstream effects of MG-0103.
  • (Phase I and II): To assess the pharmacokinetics (PK) of MG-0103 and gemcitabine.
  • (Phase I and II): To describe survival and time-to-progression in the MG-0103 + gemcitabine combination.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE A Phase I/II Study of MGCD0103 (MG-0103) in Combination With Gemcitabine
Official Title  ICMJE A Phase I/II Study of MGCD0103 (MG-0103) in Combination With Gemcitabine
Brief Summary Inthis study, MGCD0103, a new anticancer drug under investigation, is given three times weekly in combination with gemcitabine to patients with solid tumours.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Tumors
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Experimental: 1
  • Drug: MGCD0103
  • Drug: Gemcitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 17, 2008)
Original Enrollment  ICMJE
 (submitted: September 6, 2006)
Actual Study Completion Date  ICMJE December 2008
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00372437
Other Study ID Numbers  ICMJE 0103-006
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mirati Therapeutics Inc.
Study Sponsor  ICMJE Mirati Therapeutics Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gregory Reid, MSc, MBA MethylGene Inc.
PRS Account Mirati Therapeutics Inc.
Verification Date June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP