Alvespimycin Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors

April 9, 2013 updated by: National Cancer Institute (NCI)

Phase 1 Study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG, NSC #707545) in Patients With Solid Tumors.

This phase I trial is studying the side effects and best dose of alvespimycin hydrochloride in treating patients with metastatic or unresectable solid tumors. Drugs used in chemotherapy, such as alvespimycin hydrochloride, work in different ways to stop tumor cells from dividing so they stop growing or die.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the toxic effects and maximum tolerated dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with metastatic or unresectable solid tumors.

SECONDARY OBJECTIVES:

II. Determine the effects of this drug on the expression of Hsp90 client proteins in normal and tumor tissue samples from these patients.

OUTLINE: This is a dose-escalation study.

Patients receive alvespimycin hydrochloride IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-2 patients receive accelerated escalating doses of alvespimycin hydrochloride until at least 1 of 2 patients experience dose-limiting toxicity (DLT). Cohorts are then expanded to 3-6 patients who receive escalating doses (in a standard manner) of alvespimycin hydrochloride 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 DLT. Once the MTD is determined, 10 additional patients are treated at that dose.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed solid tumor, including, but not limited to, the following:

    • Prostate
    • Breast
    • Ovary
    • Colon
    • Kidney
    • Head and neck
    • Stomach
    • Melanoma
  • Metastatic or unresectable disease
  • No standard curative or palliative therapy exists or is no longer effective

  • Progressive disease as indicated by the following:

    • Non-prostate cancer

      • New lesions or increase in pre-existing lesions on bone scintigraphy, CT scan, MRI, or by physical examination
      • No increase in biochemical markers (e.g., carcinoembryonic antigen or CA-15-3) or symptoms as sole evidence of disease progression

    • Prostate cancer

      • Must have castrate metastatic disease (i.e., disease progression after castration or treatment with a gonadotropin-releasing hormone [GnRH] analog)

        • Patients who have not undergone surgical orchiectomy must continue with medical therapy (i.e., GnRH analogs) to maintain castrate levels of serum testosterone < 50 ng/dL
        • Patients who received an antiandrogen as part of first-line hormonal therapy must show disease progression after discontinuing treatment

      • Progressive metastatic disease on imaging studies (e.g., bone scan, CT scan, or MRI) OR metastatic disease and a rising prostate-specific antigen (PSA) allowed

        • Biochemical progression is defined as a minimum of 3 rising PSA values from baseline obtained at least 1 week apart OR 2 rising PSA values obtained more than 1 month apart, with >= 25% increase in value
  • No active brain metastases

  • Hormone receptor status:

    • Not specified
  • Male or female
  • Performance status - Karnofsky 70-100%
  • Performance status - ECOG 0-1
  • More than 6 months
  • WBC >= 3, 000/mm^3
  • Absolute neutrophil count >= 1, 500/mm^3
  • Platelet count >= 100,000/mm^3
  • Bilirubin =< 1.5 times upper limit of normal (ULN)
  • AST and ALT < 1.5 times ULN
  • PT normal
  • Creatinine =< 1.4 mg/dL
  • Creatinine clearance > 55 mL/min
  • QTc < 450 msec for male patients (470 msec for female patients)
  • LVEF > 40% by MUGA
  • No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation >= 3 beats in a row)
  • No myocardial infarction within the past year
  • No active ischemic heart disease within the past year
  • No New York Heart Association class III or IV congestive heart failure
  • No congenital long QT syndrome
  • No left bundle branch block
  • No poorly controlled angina

  • No history of uncontrolled dysrhythmias or requiring antiarrhythmic drugs

    • Calcium blockers and beta blockers allowed
  • No other significant cardiac disease
  • Oxygen saturation > 88%
  • Dyspnea < grade 2 at rest on room air
  • No clinically significant pulmonary comorbidity (e.g., severe chronic obstructive pulmonary disease)
  • No requirement for supplemental oxygen
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active or ongoing infection
  • No symptomatic peripheral neuropathy >= grade 2
  • No psychiatric illness or social situation that would preclude study compliance
  • No other uncontrolled illness
  • More than 4 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas)
  • At least 1 week since prior ketoconazole
  • More than 4 weeks since prior radiotherapy
  • Recovered from all prior therapy
  • More than 4 weeks since prior investigational anticancer therapeutic drugs
  • No concurrent combination antiretroviral therapy for HIV-positive patients

  • No concurrent administration of any of the following herbal remedies:

    • Hydrastis canadensis (goldenseal)
    • Hypericum perforatum (St. John's wort)
    • Uncaria tomentosa (cat's claw)
    • Echinacea angustifolia roots
    • Trifolium pratense (wild cherry)
    • Matricaria chamomilla (chamomile)
    • Glycyrrhiza glabra (licorice)
    • Dillapiol
    • Hypericin
    • Naringenin
  • No other concurrent investigational agents
  • No other concurrent anticancer agents or therapies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment (alvespimycin hydrochloride)

Patients receive alvespimycin hydrochloride IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-2 patients receive accelerated escalating doses of alvespimycin hydrochloride until at least 1 of 2 patients experience DLT. Cohorts are then expanded to 3-6 patients who receive escalating doses (in a standard manner) of alvespimycin hydrochloride until MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT. Once the MTD is determined, 10 additional patients are treated at that dose.
Other: laboratory biomarker analysis
Correlative studies
Drug: alvespimycin hydrochloride
Given IV
Other Names:
  • 17-DMAG HCL
  • KOS-1022
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
MTD, defined as the dose level where the observed DLT incidence in no more than one out of six patients treated at a particular dose level
Time Frame: 28 days
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2004

Primary Completion (ACTUAL)

January 1, 2008

Study Registration Dates

First Submitted

August 4, 2004

First Submitted That Met QC Criteria

August 4, 2004

First Posted (ESTIMATE)

August 5, 2004

Study Record Updates

Last Update Posted (ESTIMATE)

April 10, 2013

Last Update Submitted That Met QC Criteria

April 9, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-01455
  • U01CA069856 (U.S. NIH Grant/Contract)
  • 04-053
  • MSKCC-04053
  • NCI-6542
  • CDR0000378288

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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