AT13387 in Treating Patients With Refractory Solid Tumors
Recruitment status was Recruiting
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Purpose
RATIONALE: AT13387 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I clinical trial is studying the side effects and best dose of AT13387 in treating patients with refractory solid tumors.
| Condition | Intervention | Phase |
|---|---|---|
|
Unspecified Adult Solid Tumor, Protocol Specific |
Drug: Hsp90 inhibitor AT13387 Other: laboratory biomarker analysis Other: pharmacological study |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase I Study of the Hsp90 Inhibitor, AT13387, in Adults With Refractory Solid Tumors |
- Safety and tolerability of Hsp90 inhibitor AT13387 (AT13387) [ Designated as safety issue: Yes ]
- Maximum-tolerated dose and recommended phase II dose of AT13387 [ Designated as safety issue: Yes ]
- Pharmacokinetics of AT13387 [ Designated as safety issue: No ]
- Pharmacodynamic markers of Hsp90 inhibition and modulation of Hsp90 client proteins by AT13387 in tumor tissue, serum, and PBMCs [ Designated as safety issue: No ]
| Estimated Enrollment: | 37 |
| Study Start Date: | November 2010 |
| Estimated Primary Completion Date: | August 2011 (Final data collection date for primary outcome measure) |
OBJECTIVES:
Primary
- Define the safety and tolerability of Hsp90 inhibitor AT13387 (AT13387) in adult patients with refractory solid tumors.
- Establish the maximum-tolerated dose (MTD) of AT13387 in adult patients with refractory solid tumors.
Secondary
- Determine the pharmacokinetics of AT13387 in patients with refractory solid tumors.
- Assess pharmacodynamic markers of Hsp90 inhibition and modulation of Hsp90 client proteins by AT13387 in tumor tissue, serum, and PBMCs.
OUTLINE: This is a dose-escalation study followed by an expansion phase.
Patients receive Hsp90 inhibitor AT13387 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood, urine, and tissue collection at baseline and periodically during the study for pharmacokinetic and pharmacodynamic studies.
After completion of study therapy, patients are followed up for 30 days.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically confirmed solid tumor malignancy
- Metastatic or unresectable disease for which no standard curative measures exist OR failed ≥ 1 line of standard therapy
- Measurable or evaluable disease
Archived tumor tissue must be HER2/neu ≥ 1+ by IHC (expansion phase)
- Disease amenable to biopsy
No known brain metastases or carcinomatous meningitis
- Brain metastatic disease that has remained stable for ≥ 2 months after treatment, without steroids or anti-seizure medications, allowed at the discretion of the principal investigator
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy > 3 months
- ANC ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- 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 agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) prior to, during, and for 2 months after completion of study
- Willingness to undergo pre- and post-treatment biopsies (expansion phase)
No clinically significant intercurrent illnesses including, but not limited to, any of the following:
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Uncontrolled cardiac arrhythmia
- Psychiatric illness and/or social situations that would limit compliance with study requirements
- QTc > 450 msec (for men) or QTc > 470 msec (for women)
PRIOR CONCURRENT THERAPY:
- At least 4 weeks since prior chemotherapy, radiotherapy, or biologic therapy (6 weeks for nitrosoureas or mitomycin C)
- At least 2 weeks since any prior drug in an exploratory IND/phase 0 study
- Recovered from prior toxicity or adverse events
- Concurrent bisphosphonates for any cancer allowed
- No concurrent combination antiretroviral therapy for HIV-positive patients
Contacts and Locations| United States, Maryland | |
| NCI - Developmental Therapeutics Clinic | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
| Contact: Shivaani Kummar, MD 301-435-5402 kummars@mail.nih.gov | |
| Principal Investigator: | Shivaani Kummar, MD | NCI - Medical Oncology Branch |
More Information
Additional Information:
No publications provided
| Responsible Party: | Shivaani Kummar, NCI - Medical Oncology Branch |
| ClinicalTrials.gov Identifier: | NCT01245218 History of Changes |
| Obsolete Identifiers: | NCT01246102 |
| Other Study ID Numbers: | CDR0000689129, NCIDTC-11-C-0029 |
| Study First Received: | November 19, 2010 |
| Last Updated: | November 25, 2010 |
| Health Authority: | Unspecified |
Keywords provided by National Cancer Institute (NCI):
|
unspecified adult solid tumor, protocol specific |
Additional relevant MeSH terms:
|
Neoplasms |
ClinicalTrials.gov processed this record on May 16, 2013