17-Dimethylaminoethylamino-17-Demethoxygeldanamycin (17-DMAG) in Treating Patients With Metastatic Solid Tumors or Tumors That Cannot Be Removed By Surgery

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

A Cancer Research UK Phase I Trial to Evaluate the Safety, Tolerability and Pharmacokinetics of 17-Dimethylaminoethyl-amino-17-Demethoxygeldanamycin (17-DMAG) Given as a Once Weekly Infusion in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00248521
• Other study ID #: ICR-PH1/102
• Secondary ID: CDR0000442402NCI
• Status: Active, not recruiting
• Phase: Phase 1
• First received: November 3, 2005
• Last updated: August 1, 2013
• Start date: October 2005

Study information

• Verified date: March 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects and best dose of 17-DMAG in treating patients with metastatic solid tumors or tumors that cannot be removed by surgery.

Description:

OBJECTIVES:

Primary

• Determine the maximum tolerated dose, dose-limiting toxicity, and recommended phase II dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with unresectable or metastatic solid tumors.

• Determine the feasibility, safety, and toxicity profile of this drug in these patients.

Secondary

• Determine the clinical pharmacokinetic profile of this drug in these patients.

• Determine tumor response in patients treated with this drug.

• Determine the biologically effective dose.

OUTLINE: This is an open-label, non-randomized, dose-escalation, multicenter study.

Patients receive 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) IV over 1 hour on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 17-DMAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD.

After completion of study treatment, patients are followed for 28 days.

PROJECTED ACCRUAL: Approximately 25-35 patients will be accrued for this study within 12-18 months.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 35
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumor

• Unresectable or metastatic disease

• Standard curative or palliative measures do not exist OR are no longer effective OR patient refused such measures

• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count > 1,500/mm^3

• Platelet count = 100,000/mm^3

• Hemoglobin = 9.0 g/dL

Hepatic

• Bilirubin normal

• ALT and AST = 1.5 times upper limit of normal

• No chronic liver disease

• Hepatitis B or C negative

Renal

• Creatinine normal OR

• Creatinine clearance normal

Cardiovascular

• No symptomatic New York Heart Association class III-IV cardiac disease

• No myocardial infarction within the past year

• No active ischemic heart disease within the past year

• No poorly controlled angina

• No uncontrolled dysrhythmia or dysrhythmias requiring antiarrhythmic drugs

• No transient ischemic attack

• No stroke

• No peripheral vascular disease

• No congenital long QT syndrome

• No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation = 3 beats in a row)

• QTc < 450 msec (for men) and 470 msec (for woman)

• LVEF > 40% by MUGA

• No left bundle branch block

Pulmonary

• No symptomatic pulmonary disease requiring medication, including any of the following:

• Dyspnea with or without exertion

• Paroxysmal nocturnal dyspnea

• Oxygen requirement

• Significant pulmonary disease (e.g., chronic obstructive/restrictive pulmonary disease

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception 4 weeks before, during, and for 6 months after completion of study treatment

• No known HIV positivity

• No other malignancy within the past 5 years except adequately treated cone biopsied carcinoma in situ of the cervix or basal cell or squamous cell skin cancer

• No ongoing or active infection

• No diabetes mellitus (with evidence of severe peripheral vascular disease or ulcers)

• No psychiatric illness or social situation that would preclude study compliance

• No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior immunotherapy

• Concurrent epoetin alfa allowed

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

• No prior 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)

Endocrine therapy

• More than 4 weeks since prior endocrine therapy

• Concurrent luteinizing hormone-releasing hormone analogues for androgen-insensitive prostate cancer and rising prostate-specific antigen allowed

Radiotherapy

• More than 4 weeks since prior radiotherapy (except for palliative treatment)

• No prior irradiation field that potentially included the heart (e.g., mantle)

Surgery

• Not specified

Other

• Recovered from all prior therapy

• Concurrent bisphosphonates allowed

• At least 5 half-lives since prior and no concurrent medication that prolong QTc

• No other concurrent anticancer or investigational agents

• No concurrent grapefruit juice

Study Design

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• alvespimycin hydrochloride

Locations

Country	Name	City	State
United Kingdom	Belfast City Hospital Trust Incorporating Belvoir Park Hospital	Belfast	Northern Ireland
United Kingdom	Institute of Cancer Research - Sutton	Sutton	England
United Kingdom	Royal Marsden - Surrey	Sutton	England

Sponsors (2)

Lead Sponsor	Collaborator
Institute of Cancer Research, United Kingdom	National Cancer Institute (NCI)

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Pacey SC, Wilson RH, Walton M, et al.: A phase I trial of the heat shock protein 90 (HSP90) inhibitor alvespimycin (17-dimethylaminoethylamino-17-demethoxygeldanamycin 17-DMAG) administered weekly, intravenously, to patients with advanced solid tumors. [A

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended phase II dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) at 28 days after treatment			Yes
Secondary	Heat shock protein 90 (HSP90) client protein and co-chaperone changes up to 29 days after treatment			No
Secondary	Tumor response by RECIST criteria every 6 weeks while on study			No
Secondary	Clinical pharmacokinetic profile established during the first course of treatment			No