Safety Study of 188Re-PTI-6D2 in Patients With Metastatic Melanoma
The purpose of this first-in-man study is to evaluate the safety of 188Re-PTI-6D2 in patients with metastatic melanoma. All patients will receive a tracer dose of 188Re-PTI-6D2 in order to provide information on how the monoclonal antibody is distributed throughout the body and to assess tumor targeting. No therapeutic dose of radiation will be given in the first study.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-Label Phase I Safety, Pharmacokinetic & Dosimetry Study of 188Re-PTI-6D2 in Patients With Metastatic Melanoma|
- To select the amount of unlabeled PTI-6D2 to administer immediately prior to a tracer dose of 188Re-PTI-6D2 in order to achieve preferred tumor targeting
- To generate pharmacokinetic (PK) and biodistribution data of 188Re-PTI-6D2 in patients with metastatic melanoma in order to estimate radiation doses absorbed to tumor and critical organs
- To determine the frequency of HAMA response associated with 188Re-PTI-6D2 administration
|Study Start Date:||May 2007|
|Primary Completion Date:||June 2008 (Final data collection date for primary outcome measure)|
This study will evaluate the safety and feasibility of the administration of 188Re-PTI-6D2 in patients with metastatic melanoma. Patients with confirmed Stage IIIc (unresectable) or Stage IV melanoma who meet all eligibility criteria will undergo a thorough physical examination and baseline tumor imaging (whole body 18FDG PET/CT and MRI brain) to document all sites of tumor.
Treatment will be administered on an inpatient basis. An initial cohort of 3 patients will receive a tracer dose of 188Re-PTI-6D2 without any preceding unlabeled antibody. The tracer dose will consist of 10 mCi of rhenium-labeled antibody; the amount of antibody (in mg) will depend on specific activity and is estimated to range from 2 to 10 mg. Additional cohorts of three patients each will receive 10 mg, 20 mg, and 50 mg of unlabeled PTI-6D2 immediately preceding administration of the tracer dose. Patients will undergo serial gamma scans and SPECT/CT imaging at specified time points. Blood samples will be obtained prior to dosing and at specified intervals for PK measurements of the mAb as well as for measurement of serum radioactivity. Urine will also be collected for all patients to measure excreted radioactivity. Patients will be closely monitored for safety throughout the duration of the study.
Patients will remain at the study center for 48 hours after infusion to allow adequate time for post-treatment safety observation, monoclonal antibody clearance and rhenium decay. Prior to the escalation of the dose of unlabeled PTI-6D2, safety data from the inpatient period and 2-week follow-up visit for the three patients at the current dose level will be reviewed. If there is no evidence of a safety risk, the dose of unlabeled PTI-6D2 will be escalated for the next cohort of patients. Dose escalation of unlabeled antibody will occur according to a specific scheme.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00399113
|Hadassah Hebrew University Hospital|
|Jerusalem, Israel, 91120|
|Chaim Sheba Medical Center|
|Tel Hashomer, Israel, 52621|
|Principal Investigator:||Eithan Galun, M.D.||Hadassah Hebrew University Hospital|
|Principal Investigator:||Jacob Schachter, M.D.||Chaim Sheba Medical Center|
|Principal Investigator:||Tzila Zwas, M.D.||Chaim Sheba Medical Center|