INCLUSION CRITERIA
Patients must have histologically confirmed (at the treating institution) solid tumor malignancy or lymphoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are associated with minimal patient survival benefit (as defined by the patient and/or their physician). Enrollment of patients with tumors that can be safely biopsied is encouraged. Measurable disease is not required.
Patients must have recovered to less than grade 1 CTCAEv3 from toxicity of prior chemotherapy or biologic therapy and must not have had prior chemotherapy or biologic therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C, 8 weeks for UCN-01). Patients must be at least 1 month since any prior radiation or major surgery. Patients on bisphosphonates for any cancer or on hormone therapy for prostate cancer, however, will not need to discontinue this therapy in order to be eligible. However, prostate cancer patients will need to have metastatic prostate cancer that has progressed despite hormonal therapy. Castrate testosterone levels occur within hours after castration and within 2-3 weeks of a LHRH agonist. The current standard is to continue androgen suppression despite progressive disease.
Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of 17-DMAG in patients less than 18 years of age, children are excluded from this study. Appropriate studies in the pediatric age group may be undertaken as indicated.
ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
Life expectancy of greater than 3 months.
3.1.6 Patients must have normal organ and marrow function as defined below:
Hb greater than 8 g/dL
leukocytes greater than or equal to 3,000/ microL
absolute neutrophil count greater than or equal to 1,500/ microL
platelets greater than or equal to 100,000/ microL
total bilirubin within normal institutional limits
AST (SGOT)/ALT (SGPT) less than or equal to 1 X institutional upper limit of normal
creatinine within normal institutional limits
OR
creatinine clearance greater than or equal to 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
PT, PTT within normal limits
The effects of 17-DMAG on the developing human fetus are unknown. For this reason and because chemotherapeutic agents in general are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Women of child bearing potential must have a negative pregnancy test in order to be eligible. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Ability to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA
Patients who have had chemotherapy, biologic therapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C, 8 weeks for UCN-01) prior to entering the study or those who have not recovered to less than or equal to grade 1 from adverse events due to agents administered more than 4 weeks earlier.
Patients may not be receiving any other investigational agents.
Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 6 months without steroids or anti-seizure medications may be enrolled at the discretion of the principal investigator.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to 17-DMAG (geldanamycin, 17-AAG).
Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patients taking more than preventive doses of aspirin or NSAIDs, or on full anti-coagulation on a regular basis will also be excluded due to hemorrhage noted in animal studies.
Pregnant women are excluded from this study because 17-DMAG is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 17-DMAG, breastfeeding should be discontinued if the mother is treated with 17-DMAG.
Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, patients with known immune deficiency syndromes or who are HIV positive will be excluded from the study. HIV-positive patients with disease controlled by combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with 17-DMAG. Appropriate studies will be undertaken in these patients when indicated.
Patients with baseline hyponatremia less than 130 mmol/L or orthostatic hypotension greater than Grade 2 (requiring more than brief fluid replacement or other therapy or with physiologic consequences) and/or not corrected to serum sodium greater than 130 mmol/L or orthostatic hypotension at most Grade 1 (changes, intervention not needed) with up to 2 L 0.9% sodium chloride infusion.
INCLUSION OF WOMEN AND MINORITIES
Both men and women and members of all races and ethnic groups are eligible for this trial.