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

NCT00372437 | Completed Phase 1

• 1 other identifier: 0103-006
• Study Type: interventional
• Target: 47
• Locations: 2 countries
• Sites: 8

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.

Conditions

Tumors

Keywords

Refractory solid tumors; Phase I/II; Refractory and solid tumors

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose in combination with azacitidine

  1 year (anticipated)

• Response rate

  1 year (anticipated)

Secondary Outcomes (2)

• Objective response.

  1 year (anticipated)

• Pharmacodynamics (histone acetylation, biomarkers)

  1 year (anticipated)

Study Arms (1)

1

EXPERIMENTAL

Drug: MGCD0103; Drug: Gemcitabine

Interventions

MGCD0103 DRUG

MGCD0103 as an oral dose three times per week.

1

Gemcitabine DRUG

Gemcitabine 1000mg/m\<2\> intravenously days 1, 8, 15 of a 28 day cycle.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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+.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mirati Therapeutics Inc.: lead

Study Sites (8)

Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Veterans Affairs Medical Center

Kansas City, Kansas, 64128, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Pennsylvania Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104-4283, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-6307, United States

Location

McGill University/Dept Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

CHUS Hopital Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada

Location

MeSH Terms

Conditions

Neoplasms

Interventions

mocetinostat; Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Gregory Reid, MSc, MBA

  MethylGene Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2006
• First Posted: September 7, 2006
• Study Start: September 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: July 1, 2015

Record last verified: 2015-06

Locations

US (6); CA (2)