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Alvespimycin Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors

Phase 1
Completed
Conditions
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
Interventions
Other: laboratory biomarker analysis
Other: pharmacological study
Registration Number
NCT00089362
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
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

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (alvespimycin hydrochloride)alvespimycin hydrochloridePatients 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.
Treatment (alvespimycin hydrochloride)laboratory biomarker analysisPatients 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.
Treatment (alvespimycin hydrochloride)pharmacological studyPatients 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.
Primary Outcome Measures
NameTimeMethod
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 level28 days
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

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