Patient case: 54-year-old male with Gastric cancer. Genetic variant: PIK3CA (E545K). Other conditions: Depression.

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

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: 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

Relevance to patient case: not relevant