Chemotherapy in Treating Patients With Refractory Advanced Solid Tumors or Hematologic Cancer

• ClinicalTrials.gov Identifier: NCT00004065
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Last Update Posted: June 24, 2013
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by: Memorial Sloan Kettering Cancer Center

Tracking Information

• First Submitted Date: December 10, 1999
• First Posted Date: January 27, 2003
• Last Update Posted Date: June 24, 2013
• Study Start Date: July 1999
• Actual Primary Completion Date: March 2005 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures: Not Provided
• Original Primary Outcome Measures: Not Provided
• Change History: Complete list of historical versions of study NCT00004065 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Primary Purpose: Treatment

Condition

• 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

• Intervention: Drug: tanespimycin
• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Enrollment: Not Provided
• Original Enrollment: Not Provided
• Actual Study Completion Date: March 2005
• Actual Primary Completion Date: March 2005 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00004065
• Other Study ID Numbers: 99-037; CDR0000067267 ( Registry Identifier: PDQ (Physician Data Query) ); NCI-T99-0035; UCLA-0206019
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: Howard I. Scher, MD; Memorial Sloan Kettering Cancer Center

• PRS Account: Memorial Sloan Kettering Cancer Center
• Verification Date: June 2013