Clinical trial NCT00089362: Alvespimycin Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors
Official title: Phase 1 Study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG, NSC #707545) in Patients With Solid Tumors.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-08-05
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: David Solit
role: PRINCIPAL_INVESTIGATOR
References: