Clinical trial NCT00004065: Chemotherapy in Treating Patients With Refractory Advanced Solid Tumors or Hematologic Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Keywords: 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
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin in treating patients with refractory advanced solid tumors or hematologic cancers.

Detailed description: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Howard I. Scher, MD
role: STUDY_CHAIR
References: