PU-H71 in Patients With Solid Tumors and Low-Grade Non-Hodgkin s Lymphoma That Have Not Responded to Standard Treatment
- 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.
- To evaluate the safety and effectiveness of PU-H71 in solid tumors and non-Hodgkin's lymphoma that have not responded to standard treatments.
- Individuals at least 18 years of age who have solid tumors or non-Hodgkin s lymphoma that have not responded to standard treatments.
- 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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of the Hsp90 Inhibitor, PU-H71, in Patients With Refractory Solid Tumors and Low-Grade Non-Hodgkin's Lymphoma|
- To establish the safety and tolerability of PU-H71 [ Time Frame: Cycle 1 (21 days) ] [ Designated as safety issue: Yes ]
- To determine the pharmacokinetics of PU-H71 [ Time Frame: Cycle 1 ] [ Designated as safety issue: No ]
|Study Start Date:||April 2011|
|Study Completion Date:||September 2014|
|Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
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.
-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.
- To establish the safety and tolerability of PU-H71 administered on a once weekly, 2 weeks out of 3 schedule, in patients with refractory solid tumors and lowgrade non-Hodgkin s lymphoma (NHL).
- To establish the MTD and the RP2D of PU-H71 administered on a once weekly, 2 weeks out of 3 schedule, in patients with refractory solid tumors and low-grade NHL.
- To determine the pharmacokinetics of PU-H71 administered on a once weekly, 2 weeks out of 3 schedule, in patients with refractory solid tumors and low-grade NHL.
- To perform pharmacodynamic studies to ascertain PU-H71 effect on HSP70 in tumor tissue, serum, and PBMCs at the MTD.
- To perform pharmacodynamic studies to ascertain PU-H71 effect on HSP90 client proteins in tumor tissue at the MTD.
-Study participants must have histologically confirmed solid tumor malignancy or low-grade non-Hodgkin s lymphoma that has progressed or recurred after at least one line of chemotherapy or for which no standard treatment option exists; no therapy within 4 weeks prior to entering the study; age greater than or equal to 18 years; ECOG less than or equal to 2; life expectancy > 3 months; and adequate organ and marrow function. Patients entering on the expansion cohort at the MTD must have disease amenable to biopsy with willingness to undergo pre- and post-treatment biopsies.
- This study will follow a modified accelerated titration design (Simon et al., 1997).
- The accelerated phase ends when 1 patient experiences a dose-limiting toxicity or 2 patients experience Grade 2 drug-related toxicity during the first cycle; after which the study will follow the standard 3 + 3 design.
- PU-H71 will be administered intravenously over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days.
- PK and PD studies will be conducted during cycle 1. Up to 10 additional patients will be entered at the MTD to further define toxicity and perform PD studies at this dose; pre- and post-treatment tumor biopsies will be mandatory for these patients.
- CT scans will be performed at baseline and every 2 cycles (6 weeks) for restaging.
- Up to 100 patients may be treated.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01581541
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Alice P Chen, M.D.||National Cancer Institute (NCI)|