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

Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00372437
• Other study ID #: 0103-006
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 5, 2006
• Last updated: June 4, 2015
• Start date: September 2006
• Est. completion date: December 2008

Study information

• Verified date: June 2015
• Source: Mirati Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tumors

Intervention

Drug:
• MGCD0103
MGCD0103 as an oral dose three times per week.
• Gemcitabine
Gemcitabine 1000mg/m<2> intravenously days 1, 8, 15 of a 28 day cycle.

Locations

Country	Name	City	State
Canada	McGill University/Dept Oncology	Montreal	Quebec
Canada	CHUS Hopital Fleurimont	Sherbrooke	Quebec
United States	Gabrail Cancer Center	Canton	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Veterans Affairs Medical Center	Kansas City	Kansas
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Pennsylvania Presbyterian Medical Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose in combination with azacitidine		1 year (anticipated)	Yes
Primary	Response rate		1 year (anticipated)	No
Secondary	Objective response.		1 year (anticipated)	No
Secondary	Pharmacodynamics (histone acetylation, biomarkers)		1 year (anticipated)	No