Phase I Study of the Hsp90 Inhibitor, PU-H71, in Patients With Refractory Solid Tumors and Low-Grade Non-Hodgkin's Lymphoma

Inclusion Criteria

- INCLUSION CRITERIA:

- Patients must have histologically documented (confirmed at the Laboratory of
Pathology, NCI) solid tumor malignancy or low-grade non-Hodgkin s lymphoma that is
metastatic or unresectable, for which standard curative measures do not exist, or
whose disease has progressed or recurred following at least one line of standard
therapy.

- Patients must have measurable or evaluable disease.

- Patients must have completed any chemotherapy, radiation therapy, or biologic therapy
greater than or equal to 4 weeks prior to entering the study (6 weeks for
nitrosoureas or mitomycin C).

Patients must be greater than or equal to 2 weeks since any prior administration of a
study drug in a Phase 0 study (also referred to as a pre-Phase I study where a
sub-therapeutic dose of drug is administered). Patients must have recovered to eligibility
levels from prior toxicity or adverse events. Patients receiving bisphosphonates for any
cancer are eligible to participate.

- Age greater than or equal to 18 years.

- An Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
2.

- Life expectancy > 3 months.

- Patients must have normal or adequate organ and marrow function as defined below:

- Absolute neutrophil count greater than or equal to 1,500/microL

- Platelets greater than or equal to 100,000/microL

- Total bilirubin less than or equal to 1.5 times institutional ULN

- AST (SGOT)/ALT (SGPT) less than or equal to 2.5 times institutional ULN

- Creatinine < 1.5 times ULN; OR

- Measured creatinine greater than or equal to 60 mL/minute for patients with
clearance creatinine levels greater than or equal to 1.5 times ULN

- The effects of PU-H71 on the developing human fetus are unknown. For this reason,
women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control or abstinence) prior to study entry, for
the duration of study participation, and for 2 months after completion of study.
Women of childbearing potential must have a negative pregnancy test within 72 hours
of enrollment in order to be eligible. Should a woman become pregnant or suspect she
is pregnant while she or her partner is participating in the study, the treating
physician should be notified immediately. Because there is an unknown but potential
risk to nursing infants secondary to treatment of the mother with PU-H71,
breastfeeding should be discontinued if the mother is treated with PU-H71.

- During the expansion phase of the protocol, patients must have:

- Disease amenable to biopsy

- Willingness to undergo pre- and post-treatment tumor biopsies

- Ability to understand and the willingness to sign a written informed consent
document.

EXCLUSION CRITERIA:

- Patients with known brain metastases or carcinomatous meningitis are excluded from
this clinical trial, with the exception of patients whose brain metastatic disease
status has remained stable for greater than or equal to 3 months after treatment of
the brain metastases.

- Patients with clinically significant intercurrent illnesses, including but not
limited to, symptomatic congestive heart failure, unstable angina pectoris,
uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements.

- QTc > 450 msec for men and > 470 msec for women.

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for PK interactions with PU-H71.

- Pregnant women are ineligible because the effects of PU-H71 on the developing human
fetus are unknown. Breastfeeding should be discontinued if the mother is treated with
PU-H71 since there is an unknown but potential risk for adverse events in nursing
infants.