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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2008 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00248521
First received: November 3, 2005
Last updated: August 1, 2013
Last verified: March 2008

November 3, 2005
August 1, 2013
October 2005
January 2007   (final data collection date for primary outcome measure)
Recommended phase II dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) at 28 days after treatment [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00248521 on ClinicalTrials.gov Archive Site
  • Heat shock protein 90 (HSP90) client protein and co-chaperone changes up to 29 days after treatment [ Designated as safety issue: No ]
  • Tumor response by RECIST criteria every 6 weeks while on study [ Designated as safety issue: No ]
  • Clinical pharmacokinetic profile established during the first course of treatment [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
17-Dimethylaminoethylamino-17-Demethoxygeldanamycin (17-DMAG) in Treating Patients With Metastatic Solid Tumors or Tumors That Cannot Be Removed By Surgery
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

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Unspecified Adult Solid Tumor, Protocol Specific
Drug: alvespimycin hydrochloride
Not Provided
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. [Abstract] American Association for Cancer Research: Molecular Targets and Cancer Therapeutics, October 22-26, 2007, San Francisco, CA A-PR-6, 2007.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
35
Not Provided
January 2007   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT00248521
ICR-PH1/102, CDR0000442402, NCI-6547
Not Provided
Not Provided
Institute of Cancer Research, United Kingdom
National Cancer Institute (NCI)
Study Chair: Ian R. Judson, MA, MD, FRCP Institute of Cancer Research, United Kingdom
National Cancer Institute (NCI)
March 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP