Clinical trial NCT00697632: Safety Study of Oral MGCD265 Administered Without Interruption to Subjects With Advanced Malignancies
Official title: Open-Label Dose-Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Daily Oral MGCD265 Administered Without Interruption to Subjects With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Keywords: MET
AXL
VEGFR
NSCLC
HNSCC (Head and neck squamous cell carcinoma)
Tumor
Safety
Phase 1
Solid tumor
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2008-06-16
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this study, MGCD265, a new anticancer drug under investigation, is given daily to patients with advanced malignancies to study its safety profile.

Detailed description: MGCD265 belongs to a new class of drugs with anticancer potential, known as tyrosine kinase inhibitors. MGCD265 was shown to slow down the growth of human cancer cells in mice. Clinical studies are being pursued to evaluate the safety of MGCD265 in cancer patients.

In this study, MGCD265 is orally administered on a daily basis to patients with advanced malignancies.

Eligibility criteria: Inclusion Criteria:

* Advanced metastatic or unresectable malignancy that is refractory to standard therapy and/or existing therapies are not likely to achieve clinical benefit, and/or the patient declines to receive standard treatment such as chemotherapy.
* Evaluable disease;
* Last dose of prior chemotherapy, radiation therapy, or investigational agents occurred at least 4 weeks before the start of therapy;
* Recovery from the adverse effects ≤ grade 1;
* Acceptable ECOG status 0, 1, or 2;
* Life expectancy greater than 3 months following study entry;
* Adequate laboratory values;
* For patients enrolling in the four expansion cohorts:

  * NSCLC patients must meet criteria for MET and/or Axl expression or,
  * HNSCC patients must meet criteria for MET and/or Axl expression or,
  * NSCLC patients must meet criteria for amplification of the MET gene locus, defined MET mutations, or rearrangements involving the AXL or MET gene locus or;
  * Patients with tumor types such as HNSCC, papillary renal carcinoma, gastric adenocarcinoma, and other solid tumors must meet criteria for amplification of the MET gene locus, defined MET mutations, or rearrangements involving the AXL or MET gene locus

Exclusion Criteria:

* Uncontrolled concurrent illness;
* History of cardiovascular illness;
* QTc \> 470 msec (including subjects on medication);
* Left ventricular ejection fraction (LVEF) \< 50%;
* Immunocompromised subjects;
* History of bone marrow transplant;
* Lung tumor lesions with increased likelihood of bleeding;
* Symptomatic or uncontrolled brain metastases;
* Unable to swallow oral medications or with pre-existing gastrointestinal disorders.

Primary outcomes:
measure: Safety and tolerability
timeFrame: 1 year [Anticipated]
Secondary outcomes:
measure: Pharmacokinetics
timeFrame: 1 year [Anticipated]
measure: Pharmacodynamics
timeFrame: 1 year [Anticipated]
measure: Clinical response
timeFrame: 1 year [Anticipated]
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: San Diego
country: United States
facility: UC San Diego
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University, Alvin J. Siteman Cancer Center
state: Missouri
city: New York
country: United States
facility: Columbia University, Herbert Irving Comprehensive Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas, MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency, Vancouver Center
state: British Columbia
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hosptial
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
Study officials:
References: