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Alvespimycin Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00089362
First received: August 4, 2004
Last updated: April 9, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Male Breast Cancer
Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
Recurrent Basal Cell Carcinoma of the Lip
Recurrent Breast Cancer
Recurrent Colon Cancer
Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Recurrent Gastric Cancer
Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Recurrent Lymphoepithelioma of the Nasopharynx
Recurrent Lymphoepithelioma of the Oropharynx
Recurrent Melanoma
Recurrent Metastatic Squamous Neck Cancer With Occult Primary
Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Recurrent Mucoepidermoid Carcinoma of the Oral Cavity
Recurrent Ovarian Epithelial Cancer
Recurrent Prostate Cancer
Recurrent Renal Cell Cancer
Recurrent Salivary Gland Cancer
Recurrent Squamous Cell Carcinoma of the Hypopharynx
Recurrent Squamous Cell Carcinoma of the Larynx
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Nasopharynx
Recurrent Squamous Cell Carcinoma of the Oropharynx
Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Recurrent Verrucous Carcinoma of the Larynx
Recurrent Verrucous Carcinoma of the Oral Cavity
Stage III Adenoid Cystic Carcinoma of the Oral Cavity
Stage III Basal Cell Carcinoma of the Lip
Stage III Colon Cancer
Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Stage III Gastric Cancer
Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Stage III Lymphoepithelioma of the Nasopharynx
Stage III Lymphoepithelioma of the Oropharynx
Stage III Melanoma
Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Stage III Mucoepidermoid Carcinoma of the Oral Cavity
Stage III Ovarian Epithelial Cancer
Stage III Renal Cell Cancer
Stage III Salivary Gland Cancer
Stage III Squamous Cell Carcinoma of the Hypopharynx
Stage III Squamous Cell Carcinoma of the Larynx
Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage III Squamous Cell Carcinoma of the Nasopharynx
Stage III Squamous Cell Carcinoma of the Oropharynx
Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage III Verrucous Carcinoma of the Larynx
Stage III Verrucous Carcinoma of the Oral Cavity
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Adenoid Cystic Carcinoma of the Oral Cavity
Stage IV Basal Cell Carcinoma of the Lip
Stage IV Breast Cancer
Stage IV Colon Cancer
Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Stage IV Gastric Cancer
Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Stage IV Lymphoepithelioma of the Nasopharynx
Stage IV Lymphoepithelioma of the Oropharynx
Stage IV Melanoma
Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Stage IV Mucoepidermoid Carcinoma of the Oral Cavity
Stage IV Ovarian Epithelial Cancer
Stage IV Prostate Cancer
Stage IV Renal Cell Cancer
Stage IV Salivary Gland Cancer
Stage IV Squamous Cell Carcinoma of the Hypopharynx
Stage IV Squamous Cell Carcinoma of the Larynx
Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Stage IV Squamous Cell Carcinoma of the Oropharynx
Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IV Verrucous Carcinoma of the Larynx
Stage IV Verrucous Carcinoma of the Oral Cavity
Unspecified Adult Solid Tumor, Protocol Specific
Untreated Metastatic Squamous Neck Cancer With Occult Primary
Drug: alvespimycin hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG, NSC #707545) in Patients With Solid Tumors.

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: July 2004
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: alvespimycin hydrochloride
Given IV
Other Names:
  • 17-DMAG HCL
  • KOS-1022
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00089362

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Investigators
Principal Investigator: David Solit Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00089362     History of Changes
Other Study ID Numbers: NCI-2012-01455, 04-053, MSKCC-04053, NCI-6542, CDR0000378288, U01CA069856
Study First Received: August 4, 2004
Last Updated: April 9, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Carcinoma
Carcinoma, Adenoid Cystic
Carcinoma, Basal Cell
Carcinoma, Mucoepidermoid
Carcinoma, Renal Cell
Carcinoma, Squamous Cell
Carcinoma, Verrucous
Colonic Neoplasms
Esthesioneuroblastoma, Olfactory
Granuloma
Head and Neck Neoplasms
Laryngeal Diseases
Laryngeal Neoplasms
Melanoma
Nasopharyngeal Neoplasms
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Unknown Primary
Oropharyngeal Neoplasms
Ovarian Neoplasms
Papilloma
Papilloma, Inverted
Paranasal Sinus Neoplasms
Prostatic Neoplasms
Salivary Gland Neoplasms
Stomach Neoplasms
Adenocarcinoma
Adnexal Diseases

ClinicalTrials.gov processed this record on November 25, 2014