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A Phase I Trial of 17-N-Allylamino-17-Demethoxy Geldanamycin (17-AAG, NSC #330507) Daily X 5 in Patients With Advanced Cancer Therapeutic Protocol


Phase 1
18 Years
N/A
Not Enrolling
Both
Bladder Cancer, Breast Cancer, Colorectal Cancer, Gastric Cancer, Head and Neck Cancer, Kidney Cancer, Leukemia, Lung Cancer, Melanoma (Skin), Ovarian Cancer, Prostate Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Trial of 17-N-Allylamino-17-Demethoxy Geldanamycin (17-AAG, NSC #330507) Daily X 5 in Patients With Advanced Cancer Therapeutic Protocol


OBJECTIVES:

- Determine the maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin
(17-AAG) in patients with refractory or advanced solid tumors or hematologic
malignancies.

- Evaluate the effects of this drug on the expression of signaling proteins present on an
individual patient's cancer at the start of treatment and, if possible, post treatment.

OUTLINE: This is a two-phase, dose-escalation, multicenter study. Patients are stratified
according to disease (chronic myelogenous leukemia [CML] or Philadelphia chromosome [Ph]+
acute lymphoblastic leukemia [ALL] vs solid tumor).

Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 60-90 minutes
twice weekly. Courses repeat every 12 weeks in the absence of disease progression (after at
least 2 courses for CML or Ph+ ALL patients) or unacceptable toxicity.

- Accelerated phase: Single patients receive escalating dose levels of 17-AAG until one
patient experiences a first course grade 3 or greater toxicity or two different
patients experience grade 2 toxicity during any course.

- Standard phase: Cohorts of 3-6 patients in each stratum receive escalating doses of
17-AAG 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.

PROJECTED ACCRUAL: Approximately 51 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following:

- Histologically confirmed advanced primary or malignant solid tumor refractory to
standard therapy or for which no curative standard therapy exists

- Progressive disease evidenced by 1 of the following:

- Non-prostate cancer (including, but not limited to, breast, ovary,
head and neck, non-small cell lung, bladder, kidney, colon, stomach,
or malignant melanoma)

- Development of new lesions or an increase in existing lesions

- No increase in a biochemical marker (e.g., carcinoembryonic
antigen, CA-15-3, or an increase in symptoms) as sole measure of
disease

- Prostate cancer (androgen independent) meeting the following criteria:

- Progressing metastatic disease on bone scan, CT scan, or MRI

- Metastatic disease and rising prostate-specific antigen (PSA) values
meeting 1 of the following criteria:

- At least 3 rising PSA values obtained at least 1 week apart = 2 rising
values more than 1 month apart with at least 25% increase over the
range of values

- Serum testosterone less than 30 ng/mL

- Castrate status should be maintained by medical therapies if orchiectomy
has not been performed

- Progressive disease must be evident off antiandrogen therapy if received
prior to study entry

- Registered to protocol MSKCC-9040

- Cytologically confirmed chronic, accelerated, or blastic phase chronic
myelogenous leukemia (CML) or Philadelphia chromosome (Ph)-positive acute
lymphoblastic leukemia (ALL) refractory to standard therapy or for which no
curative therapy exists

- Progressive disease evidenced by 1 of the following:

- Accelerated or blastic phase disease that is not responsive to
standard therapy or loss of hematologic response to imatinib mesylate
while remaining in chronic phase for CML

- Relapsed or refractory after treatment with standard chemotherapy and
imatinib mesylate for Ph-positive ALL

- No active CNS or epidural tumor

- Hormone receptor status:

- Not specified

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Sex:

- Not specified

Menopausal status:

- Not specified

Performance status:

- Karnofsky 70-100%

Life expectancy:

- At least 6 months

Hematopoietic:

- WBC greater than 3,500/mm^3

- Platelet count greater than 100,000/mm^3

- No restrictions based on peripheral blood counts for CML and Ph-positive ALL

Hepatic:

- Bilirubin no greater than 1.2 times upper limit of normal (ULN)

- AST less than 1.5 times ULN

- Prothrombin time normal

Renal:

- Creatinine no greater than 1.5 times ULN OR

- Creatinine clearance greater than 60 mL/min

Cardiovascular:

- No myocardial infarction within the past 6 months

- Ejection fraction greater than 45% by radionuclide cardiac angiography

- No ventricular aneurysm or other abnormal wall motion

- No reversible defect by thallium stress test if any of the following conditions are
present:

- Ejection fraction less than 45% on radionuclide angiocardiography

- Worrisome but nonexclusive cardiovascular history

- Abnormal echocardiogram

- Patients with the following history or clinical findings require additional
diagnostic testing:

- Significant Q waves (greater than 3 mm or greater than one-third of the height
of the QRS complex)

- ST elevation or depressions of greater than 2 mm that are not attributable to
hypertension strain

- Absence of regular sinus rhythm

- Bundle branch block

- Requirement for diuretics for reasons other than hypertension or digoxin for
reasons other than atrial fibrillation

- Prior mild to moderate congestive heart failure

- No New York Heart Association class III or IV heart disease

- No angina pectoris

- No uncontrolled hypertension or intermittent claudication

- No severe debilitating valvular disease

Pulmonary:

- No severe debilitating pulmonary disease

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No active infection requiring IV antibiotics

- No symptomatic peripheral neuropathy grade 2 or higher

- No other severe medical conditions that would increase risk for toxicity

- No allergy to eggs or egg products

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 4 weeks since prior biologic therapy (including interferon for CML) and
recovered

Chemotherapy:

- At least 4 weeks since prior chemotherapy (3 days for hydroxyurea for CML or ALL) and
recovered

- No other concurrent chemotherapy

Endocrine therapy:

- See Disease Characteristics

- At least 4 weeks since prior endocrine therapy and recovered

Radiotherapy:

- At least 4 weeks since prior radiotherapy and recovered

- Concurrent radiotherapy to localized disease sites not being used to evaluate
antitumor response allowed

- No concurrent radiotherapy to only measurable lesion

Surgery:

- See Disease Characteristics

- Prior orchiectomy allowed

- No concurrent surgery

Other:

- At least 3 days since prior imatinib mesylate for CML or ALL

- At least 4 weeks since prior investigational anticancer drugs and recovered

- At least 4 weeks since prior palliative treatment for metastatic disease

- No concurrent ketoconazole, warfarin, verapamil, miconazole, or erythromycin

- No other concurrent investigational drugs

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Howard I. Scher, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

99-037

NCT ID:

NCT00004065

Start Date:

July 1999

Completion Date:

March 2005

Related Keywords:

  • Bladder Cancer
  • Breast Cancer
  • Colorectal Cancer
  • Gastric Cancer
  • Head and Neck Cancer
  • Kidney Cancer
  • Leukemia
  • Lung Cancer
  • Melanoma (Skin)
  • Ovarian Cancer
  • Prostate Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • stage III colon cancer
  • stage IV colon cancer
  • stage IV breast cancer
  • stage IIIA breast cancer
  • recurrent breast cancer
  • stage III gastric cancer
  • stage IV gastric cancer
  • recurrent gastric cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • recurrent non-small cell lung cancer
  • recurrent colon cancer
  • stage III renal cell cancer
  • stage IV renal cell cancer
  • recurrent renal cell cancer
  • stage III ovarian epithelial cancer
  • stage IV ovarian epithelial cancer
  • recurrent ovarian epithelial cancer
  • recurrent adult acute lymphoblastic leukemia
  • relapsing chronic myelogenous leukemia
  • stage III bladder cancer
  • recurrent bladder cancer
  • stage IV bladder cancer
  • stage III prostate cancer
  • stage IV prostate cancer
  • recurrent prostate cancer
  • stage III melanoma
  • stage IV melanoma
  • recurrent melanoma
  • stage IIIA non-small cell lung cancer
  • stage IIIB non-small cell lung cancer
  • stage IV non-small cell lung cancer
  • unspecified adult solid tumor, protocol specific
  • chronic phase chronic myelogenous leukemia
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • untreated metastatic squamous neck cancer with occult primary
  • recurrent metastatic squamous neck cancer with occult primary
  • ovarian stromal cancer
  • stage III ovarian germ cell tumor
  • stage IV ovarian germ cell tumor
  • recurrent ovarian germ cell tumor
  • stage III squamous cell carcinoma of the lip and oral cavity
  • stage III basal cell carcinoma of the lip
  • stage III mucoepidermoid carcinoma of the oral cavity
  • stage III adenoid cystic carcinoma of the oral cavity
  • stage IV squamous cell carcinoma of the lip and oral cavity
  • stage IV basal cell carcinoma of the lip
  • stage IV verrucous carcinoma of the oral cavity
  • stage IV mucoepidermoid carcinoma of the oral cavity
  • stage IV adenoid cystic carcinoma of the oral cavity
  • recurrent squamous cell carcinoma of the lip and oral cavity
  • recurrent basal cell carcinoma of the lip
  • recurrent verrucous carcinoma of the oral cavity
  • recurrent mucoepidermoid carcinoma of the oral cavity
  • recurrent adenoid cystic carcinoma of the oral cavity
  • stage III squamous cell carcinoma of the oropharynx
  • stage III lymphoepithelioma of the oropharynx
  • stage IV squamous cell carcinoma of the oropharynx
  • stage IV lymphoepithelioma of the oropharynx
  • recurrent squamous cell carcinoma of the oropharynx
  • recurrent lymphoepithelioma of the oropharynx
  • stage III squamous cell carcinoma of the nasopharynx
  • stage III lymphoepithelioma of the nasopharynx
  • stage IV squamous cell carcinoma of the nasopharynx
  • stage IV lymphoepithelioma of the nasopharynx
  • recurrent squamous cell carcinoma of the nasopharynx
  • recurrent lymphoepithelioma of the nasopharynx
  • stage III squamous cell carcinoma of the hypopharynx
  • stage IV squamous cell carcinoma of the hypopharynx
  • recurrent squamous cell carcinoma of the hypopharynx
  • stage III squamous cell carcinoma of the larynx
  • stage III verrucous carcinoma of the larynx
  • stage IV squamous cell carcinoma of the larynx
  • stage IV verrucous carcinoma of the larynx
  • recurrent squamous cell carcinoma of the larynx
  • recurrent verrucous carcinoma of the larynx
  • stage III squamous cell carcinoma of the paranasal sinus and nasal cavity
  • stage III inverted papilloma of the paranasal sinus and nasal cavity
  • stage III midline lethal granuloma of the paranasal sinus and nasal cavity
  • stage III esthesioneuroblastoma of the paranasal sinus and nasal cavity
  • stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
  • stage IV inverted papilloma of the paranasal sinus and nasal cavity
  • stage IV midline lethal granuloma of the paranasal sinus and nasal cavity
  • stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity
  • recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
  • recurrent inverted papilloma of the paranasal sinus and nasal cavity
  • recurrent midline lethal granuloma of the paranasal sinus and nasal cavity
  • recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity
  • borderline ovarian surface epithelial-stromal tumor
  • ovarian sarcoma
  • stage III verrucous carcinoma of the oral cavity
  • recurrent salivary gland cancer
  • stage IV salivary gland cancer
  • stage III salivary gland cancer
  • Urinary Bladder Neoplasms
  • Breast Neoplasms
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Colorectal Neoplasms
  • Head and Neck Neoplasms
  • Leukemia
  • Lung Neoplasms
  • Stomach Neoplasms
  • Melanoma
  • Ovarian Neoplasms
  • Prostatic Neoplasms

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781