Clinical trial NCT00606879: Safety Study of SGX523, a Small Molecule Met Inhibitor, to Treat Solid Tumors
Official title: A Phase I, Multi-Center, Open Label, Dose Escalation, Safety, PK and PkD Study of Orally Administered SGX523, a Small Molecule Anti-Cancer Agent, on a Twice Daily, Uninterrupted Schedule in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Cancer
Keywords: Solid tumor
Advanced Cancer
MET inhibitor
Receptor Tyrosine Kinase Inhibitor (RTKI)
Lead sponsor: SGX Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2008-02-05
Enrollment: 46
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: SGX523 is a drug which acts by blocking the function of an enzyme called MET. MET activity may be important in growth and survival of some types of cancer. This Phase I trial is studying the safety, side effects, and best dose of SGX523 when given to patients with advanced cancer, and how well it inhibits MET activity in tumors.


Eligibility criteria: Inclusion Criteria:

* Subject has the ability to understand, able, willing to comply with study procedures and follow up visits, and has provided written consent
* Pathologic evidence of solid tumor
* Failed standard therapy and deemed by the Investigator to be suitable for participation into the trial
* Laboratory values (obtained within 10 days prior to enrollment): ANC: \>= 1.5 × 109/L; Platelets: \>= 100 × 109/L; Hemoglobin: \>= 10.0 g/dL (without transfusions); Bilirubin: within normal range; AST, ALT, and alkaline phosphatase: \<= 2.5 x ULN without tumor liver involvement; Serum creatinine: within normal limits; Calculated creatinine clearance: \>= 60 mL/min/1.73 m2 for patients with creatinine \> Institutional Normal Values; PT/PTT/INR: within normal limits..
* Have IHC evidence of phospho-MET expression on tumor material no more than 12 months old. This is a requirement only for entry into the MTD dose expansion phase.
* Have no residual toxic effects of previous therapy, and undergo a washout period of at least 5 half-lives from the time of administration of the previous therapy.

Exclusion Criteria:

* Pregnant, lactating, or may become pregnant
* Cardiac disease requiring medical therapy
* Have had a major surgery within 4 weeks prior to Day 1 of the study
* Have an active, uncontrolled bacterial, viral, or fungal infection that requires ongoing systemic therapy
* Have a known active infection with HIV, hepatitis B or C
* Have psychiatric or seizure disorders that would require therapy or interfere with study participation
* Have other severe concurrent nonmalignant disease that could compromise protocol objectives, including malabsorptive conditions
* Patients receiving prohibited medications as listed in Appendix E, including drugs categorized as strong inhibitors of CYP3A4 and A5 and drugs known to have a high potential risk of liver toxicity
* Have known allergy to SGX523 formulation or its excipients (croscarmellose sodium, lactose monohydrate and magnesium steareate)
* Patients receiving anti-coagulant therapy

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: Within first 28 Days
Secondary outcomes:
measure: PK parameters: Cmin, Cmax, AUC∞, AUCtau, T1/2, Tmax, Vd, CLpo
timeFrame: To 28 Days after patient withdrawal
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Premier Onocology, California
state: California
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: Premier Onocology, California
name: Lee Rosen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sarch Cannon Research Institute
name: Howard Burris, MD
role: PRINCIPAL_INVESTIGATOR
References: