Study to Evaluate Combination Treatment of MGCD0103 and Docetaxel (Taxotere®) for Subjects With Advanced Cancer Tumors

NCT00511576 | Terminated Phase 1

• 1 other identifier: 103 PH US 2007 CL001
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to test the combination of an experimental drug known as MGCD0103 given along with an FDA-approved drug called docetaxel. This is a Phase 1 study that will look at different doses of MGCD0103 given along with docetaxel in order to better understand the effects (positive and negative) of this combination on the subject's body and disease. The study would like to find the following information:

• How long MGCD0103 and docetaxel stay in the subject's body;
• What effects, good and/or bad, MGCD0103 and docetaxel have on the subject and on his/her cancer; and
• If the genetic and chemical make-up of the subject's blood cells and tumor cells play a role in how you respond or do not respond to MGCD0103 and docetaxel.

Conditions

Breast Cancer; Lung Cancer; Pulmonary Cancer; Non-Small-Cell Lung Carcinoma; Prostate Cancer; Prostatic Cancer; Gastric Cancer; Stomach Cancer

Keywords

Advanced or Metastatic Breast Cancer; Breast Cancer; Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC); Hormone Refractory Prostate Cancer; Prostate Cancer; Gastric Cancer; Advanced Gastric Adenocarcinoma; HDAC Inhibitor; Taxotere; Docetaxel

Outcome Measures

Primary Outcomes (4)

• To determine the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), and safety profile of escalating doses of orally administered MGCD0103 in combination with two fixed doses (60 mg/m2 and 75 mg/m2) of IV docetaxel.

  15 months

• To assess the plasma pharmacokinetics (PK) of MGCD0103 (and/or its metabolites) and IV docetaxel administered in combination.

  15 months

• To evaluate potential pharmacodynamic (PD) effects of orally administered MGCD0103 in combination with IV docetaxel.

  15 months

• To determine the overall tumor response of orally administered MGCD0103 in combination with IV docetaxel according to Response Evaluation Criteria in Solid Tumors (RECIST) methodology.

  15 months

Study Arms (2)

Part 1

ACTIVE COMPARATOR

In Part 1, cohorts of three to six subjects will receive doses of MGCD0103 administered orally three times per week (TIW) in combination with 60 mg/m2 IV docetaxel administered as a 1-hour infusion on Day 1 of each 3-week (21-day) cycle. The starting dose of MGCD0103 in Part 1 will be 50 mg (approximately 25 mg/m2).

Drug: MGCD0103 & Docetaxel

Part 2

ACTIVE COMPARATOR

Part 2 will begin once the MTD for MGCD0103 in combination with 60 mg/m2 IV docetaxel has been determined and further evaluated in the expansion phase. In Part 2, cohorts of three to six subjects will receive escalating doses of MGCD0103 administered orally TIW in combination with 75 mg/m2 docetaxel administered as a 1-hour IV infusion on Day 1 of each cycle. The starting dose of MGCD0103 administered in combination with 75 mg/m2 IV docetaxel will be the MTD from Part 1 minus 25 mg.

Drug: MGCD0103 & Docetaxel

Interventions

MGCD0103 & Docetaxel DRUG

In both Parts 1 and 2, subsequent doses of MGCD0103 will be escalated in 25 mg increments until the MTD of MGCD0103 in combination with each fixed dose (60 mg/m2 or 75 mg/m2) ofIV docetaxel is determined. In both parts 1 and 2, MGCD0103 will be administered orally TIW for 3 weeks beginning on Day 1 at 1 hour prior to the start of the IV docetaxel infusion. There will be no scheduled break between cycles and no limit to the number of cycles a subject can receive provided they do not have disease progression as defined by RECIST, or a clinically significant drug-related adverse event (AE) that does not resolve or respond to treatment intervention with 3 weeks.

Also known as: MG-0103, Taxotere®

Part 1; Part 2

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• Diagnosis of malignant solid tumor (histologically or cytologically confirmed) where treatment with docetaxel is considered standard of care, or advanced solid malignancy that has failed to respond to standard therapy, or has progressed despite standard therapy, or where there is no reasonable likelihood of achieving clinical benefit with existing therapies.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Adequate organ function, including: Hemoglobin (Hgb) ≥8.0g/dL; Absolute neutrophil count (ANC) ≥1.5 x 10\<9\>/L (≥1500/mm\<3\>); Platelets ≥100 x 10\<9\>/L (≥100,000/mm\<3\>); Total bilirubin ≤1.5 x ULN (upper limit of normal); AST (SGOT) and ALT (SGPT) ≤2.5 x ULN; Alkaline phosphatase ≤5.0 x ULN; Serum creatinine ≤2.0 x ULN.
• Evidence of measurable disease (ie, at least one lesion that can accurately be measured in at least one dimension as ≥20 mm with conventional techniques or ≥10 mm with spiral CT scan). The requirement for measurable disease will not apply to subjects with prostate cancer.
• A minimum of 4 weeks elapsed since any major surgery.
• At least 4 weeks elapsed since any prior anticancer therapy (standard or investigational) and full recovery (NCI CTCAE grade 1) from the toxic effects of that treatment. Antiandrogen therapy is permitted for subjects with prostate cancer.
• For women of childbearing potential, a negative serum pregnancy test within 10 days of treatment, and use of physician-approved methods of birth control throughout the study.
• Written, informed consent, willingness, and ability to comply with all study procedures.

You may not qualify if:

• Subjects meeting any of the following criteria will not be included in the study.
• Prior taxane and HDAC inhibitor combination therapy.
• Previous or concurrent malignancy except adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
• Clinically significant cardiac disease including congestive heart failure (New York Heart Association Class III or IV), including pre-existing ventricular arrhythmia or conduction abnormality requiring medication, or cardiomyopathy.
• Active and uncontrolled clinically significant infection.
• History of melena, hematemesis, or hemoptysis within the last 3 months.
• Known central nervous system metastases controlled ≤3 months.
• Pregnant or lactating women. Women of child-bearing potential must have a negative serum pregnancy test within 10 days of starting study drug on Day 1 Cycle 1.
• Known hypersensitivity to taxanes, HDAC inhibitors, and/or any components of MGCD0103 capsules or docetaxel formulation components (eg, polysorbate 80).
• Known HIV or known active Hepatitis B or C.
• Presence of serious illness, medical condition, or other medical history, including abnormal laboratory parameters, which, in the opinion of the Investigator, would be likely to interfere with a subject's participation in the study or with the interpretation of the results.
• Any condition that will put the subject at undue risk or discomfort as a result of adherence to study procedures (eg, requirement to take MGCD0103 with a low pH beverage).

Sponsors & Collaborators

• Mirati Therapeutics Inc.: lead

Study Sites (2)

Johns Hopkins, Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Prostatic Neoplasms; Stomach Neoplasms

Interventions

mocetinostat; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

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

Study Record Dates

• First Submitted: August 3, 2007
• First Posted: August 6, 2007
• Study Start: August 1, 2007
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: January 8, 2015

Record last verified: 2015-01

Locations

US (2)