Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

SNX-5422 in Treating Patients With Solid Tumor or Lymphoma That Has Not Responded to Treatment

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Biomarker/Laboratory analysis, Treatment Active 18 and over NCI NCI-08-C-0091 08-C-0091, NCI-P07318, NCT00644072

Special Category: NIH Clinical Center trial

Objectives

Primary

1. Determine the maximum tolerated dose of Hsp90 inhibitor SNX-5422 mesylate in patients with refractory solid tumors or lymphomas.
2. Characterize the safety profile of this drug in these patients.

Secondary

1. Investigate the effects of this drug on Hsp90 client proteins using pharmacodynamic assays.
2. Investigate the effects of this drug on tumor response (by RECIST criteria) and on lymphoma response (by standardized lymphoma criteria) in these patients.
3. Determine the pharmacokinetic profile of SNX-2112 and prodrug Hsp90 inhibitor SNX-5422 mesylate in humans.

Entry Criteria

Disease Characteristics:

• Histologically documented diagnosis of 1 of the following:
  • Solid tumor
  • Lymphoid malignancy (i.e., lymphoma or chronic lymphocytic leukemia)
    • Aggressive non-Hodgkin lymphoma (NHL) must have progressed after treatment with two standard therapies
    • Indolent NHL must be considered refractory
• Refractory to standard therapy OR no acceptable standard treatment options
• Measurable or evaluable disease
• No symptomatic brain metastases
  • Patients with treated brain metastases that has remained stable for at least 3 months without steroids allowed

Prior/Concurrent Therapy:

• More than 4 weeks since prior chemotherapy or biologic therapy (> 6 weeks for nitrosoureas, mitomycin C, or UCN-01) and recovered
• No prior gastric bypass surgery
• At least 1 month since any prior radiotherapy or major surgery
• At least 2 weeks since any prior study drug in an exploratory IND/phase zero study
• No concurrent combination antiretroviral therapy in HIV-positive patients
• No other concurrent investigational agents
• No other concurrent antineoplastic therapies except androgen deprivation therapy (i.e., gonadotrophin-releasing hormone) in patients with prostate cancer
• Concurrent bisphosphonates for cancer allowed

Patient Characteristics:

• ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)
• Life expectancy > 3 months
• ANC ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 2.5 mg/dL in patients with Gilbert syndrome)
• AST and ALT ≤ 2.5 times ULN
• Creatinine < 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after completion of study therapy
• No uncontrolled medical illness including, but not limited to, any of the following:
  • Ongoing or uncontrolled, symptomatic congestive heart failure (AHA Class II or worse)
  • Uncontrolled hypertension
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirements
• No chronic diarrhea
• No gastrointestinal diseases that could affect drug absorption
• No gastrointestinal diseases that could alter the assessment of safety, including any of the following:
  • Irritable bowel syndrome
  • Ulcerative colitis
  • Crohn disease
  • Hemorrhagic coloproctitis
• No HIV positivity

Expected Enrollment

Outcomes

Maximum tolerated dose
Safety
Toxicity as assessed by NCI CTCAE v3.0

Pharmacokinetic profile of Hsp90 inhibitor SNX- 5422 mesylate and its metabolite, SNX-2112, in humans

Outline

Patients receive oral Hsp90 inhibitor SNX-5422 mesylate twice weekly in weeks 1-4. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo blood and urine sample collection for pharmacokinetic, pharmacodynamic analysis in course 1. Samples are evaluated using high performance liquid chromatography and tandem mass spectrometry to measure plasma and urine concentrations of Hsp90 inhibitor SNX-5422 mesylate and its metabolite, SNX-2112. Analyses of Hsp90 clients in peripheral blood mononuclear cells and the effect of Hsp90 inhibitor SNX-5422 on Hsp90 clients in tumor tissue are performed.

After completion of study therapy, patients are followed periodically.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research-Medical Oncology

Martin Gutierrez, MD, Principal investigator		Ph: 301-435-0591

U.S.A.
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Registry Information
Official Title		Phase I Study of SNX-5422 Mesylate in Adults with Refractory Solid Tumor Malignancies and Lymphomas
Trial Start Date		2008-02-01
Trial Completion Date		2009-06-30 (estimated)
Registered in ClinicalTrials.gov		NCT00644072
Date Submitted to PDQ		2008-03-13
Information Last Verified		2008-10-09