The First-in-human Phase I Trial of PU-H71 in Patients With Advanced Malignancies
|ClinicalTrials.gov Identifier: NCT01393509|
Recruitment Status : Active, not recruiting
First Posted : July 13, 2011
Last Update Posted : February 7, 2018
NOTE: This study is now recruiting only patients with Myeloproliferative Neoplasms (MPN). Dose escalation has been completed.
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, and the investigators have seen signs of disease control in patients with MPN. This study is currently enrolling a cohort expansion for patients with myeloproliferative neoplasms (MPN).
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Solid Tumor Lymphoma Myeloproliferative Neoplasms (MPN)||Drug: PU-H71||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||47 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||The First-in-human Phase I Trial of PU-H71 in Patients With Advanced Malignancies|
|Actual Study Start Date :||July 2011|
|Estimated Primary Completion Date :||July 2018|
|Estimated Study Completion Date :||July 2018|
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. The MPN expansion may explore different dosing schedules.
- To assess the safety of PU-H71 in patients with advanced malignancies. [ Time Frame: 2 years ]Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0. All patients enrolled who receive study drug will be eligible for these analyses.
- To assess the tolerability of PU-H71 in patients with advanced malignancies. [ Time Frame: 2 years ]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. ]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 ]Toxicity will be monitored using NCI- Common Terminology Criteria for Adverse Events version (4.0).Patients receiving at least 3 out of 4 planned doses of study drug 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 ]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 ]In a selected group of patients with advanced malignancies. All patients who undergo planned imaging will be eligible for this analysis.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01393509
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Komal Jhaveri, MD||Memorial Sloan Kettering Cancer Center|