The First-in-human Phase I Trial of PU-H71 in Patients With Advanced Malignancies
The purpose of this study is to test a new drug, called PU-H71 for the first time in humans, to find out what effects, good or bad, this new drug has on the patient and the cancer at different dose levels. PU-H71 blocks a protein called Heat Shock Protein-90 (Hsp90). Hsp90 is found in both normal and cancer cells, but may be more important in cancer cells. Attacking Hsp90 can stop the function of certain proteins that are needed for cancer cells to survive. The diseases that are part of this study may be especially sensitive to attacking Hsp90, but the investigators do not know if PU-H71 will have any effect on the disease.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The First-in-human Phase I Trial of PU-H71 in Patients With Advanced Malignancies|
- To assess the safety of PU-H71 in patients with advanced malignancies. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.
- To assess the tolerability of PU-H71 in patients with advanced malignancies. [ Time Frame: 2 years ] [ Designated as safety issue: No ]Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.
- To assess the pharmacokinetics of PU-H71 in patients with advanced malignancies. [ Time Frame: The investigators anticipate these time points to be: 5 min (+mins), 3-4, 18-24 and 44-48 hours post-injection. ] [ Designated as safety issue: No ]Blood will be drawn at the multiple time points for radioactive pharmacokinetic and metabolite analyses of 124I-PUH71
- To determine the maximum tolerated dose (MTD) based on toxicity analysis. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Toxicity will be monitored using NCI- Common Terminology Criteria for Adverse Events version (4.0). Patients receiving at least one cycle of drug, or developing a drug-related toxicity will be eligible for these analyses.
- To assess anti-tumor activity as defined by response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]complete response (CR), partial response (PR), stable disease (SD), duration of response, and progression free survival (PFS). Patients with measurable disease will be eligible for these analyses.
- To evaluate 124I-PU-H71 as a non-invasive means to determine tumor pharmacokinetics and intra-tumoral concentration [ Time Frame: 2 years ] [ Designated as safety issue: No ]In a selected group of patients with advanced malignancies. All patients who undergo planned imaging will be eligible for this analysis.
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||July 2016|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
This Phase 1 trial will be an open-label, dose-escalation study of single-agent PU-H71 in patients with advanced solid malignancies and lymphoma.
PU-H71 will be administered as an intravenous infusion over 1 hour two times a week on a 2 week on and 1 week off (Q21 day) schedule with a starting dose of 10 mg/m2. A Cycle on study will be defined as 21 days. The same schedule of administration will be used for all patients in this Phase I trial, and a MCRM (modified continual reassessment method)design will be employed.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01393509
|Contact: John Gerecitano, MD, PhD||212-639-3748|
|Contact: Shanu Modi, MD||646-888-5243|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: John Gerecitano, MD, PhD 212-639-3748|
|Contact: Shanu Modi, MD 646-888-5243|
|Principal Investigator:||John Gerecitano, MD,PhD||Memorial Sloan Kettering Cancer Center.|