PU-H71 in Patients With Solid Tumors and Low-Grade Non-Hodgkin's Lymphoma That Have Not Responded to Standard Treatment
Condition: Solid Tumors; Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: PU-H71
Intervention description: PU-H71 is a synthetic HSP90 inhibitor which can bind both open and closed conformations of HSP90. It demonstrates extended tumor retention and client protein degradation, while being rapidly cleared from normal tissues. It has shown complete tumor responses and retained sensitivity to retreatment in vivo.
Intervention MeSH terms: 9H-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-N-(1-methylethyl)-
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: Targeted Therapy; Solid Tumors; Lymphoma; Non-Hodgkin Lymphoma; Solid Tumor

Summary:

      Background:

      - PU-H71 is an experimental drug used to treat cancer. It works by blocking a protein in
      tumors. When this protein is blocked, it affects other proteins inside the cell that cancers
      need to grow. Researchers want to study whether PU-H71 is a safe and effective way to treat
      solid tumors and non-Hodgkin's lymphoma.

      Objectives:

      - To evaluate the safety and effectiveness of PU-H71 in solid tumors and non-Hodgkin's
      lymphoma that have not responded to standard treatments.

      Eligibility:

      - Individuals at least 18 years of age who have solid tumors or non-Hodgkin's lymphoma that
      have not responded to standard treatments.

      Design:

        -  Patients will be screened with a physical exam, medical history, blood tests, and
           imaging studies.

        -  Patients will receive PU-H71 as a 1-hour dose on days 1 and 8 of a 21-day cycle of
           treatment. The first treatment cycle will be done in the hospital so that patients can
           be monitored. The next treatment cycles will be done on an outpatient basis.

        -  Patients will have blood and urine tests and eye exams.

        -  Patients will provide tumor samples for study.

        -  Patients will have imaging studies to monitor tumor response to treatment.

        -  Patients will continue to take PU-H71 for as long as side effects remain tolerable and
           their tumor or lymphoma does not worsen. Study researchers may adjust the dose if
           needed.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Patients must have histologically documented (confirmed at the Laboratory of
             Pathology, National Cancer Institute (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 upper limit of
                  normal (ULN)

               -  Aspartate aminotransferase (AST)serum glutamic oxaloacetic transaminase
                  (SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase(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.

          -  Corrected QT interval (QTc) > 450 msec for men and > 470 msec for women.

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible because of the potential for pharmacokinetics (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.