The purpose of this study is to determine the recommended dose of I-131-CLR1404, a radiolabeled therapy compound, for treating subjects with cancer that does not respond to treatment or has returned. The identified recommended dose in this study will be used as the optimal dose of I-131-CLR1404 in subsequent clinical trials conducted for later phase clinical development. Subjects who meet study entry criteria will receive I-131-CLR1404. For each subject, the study will be conducted in two phases, dosimetric and therapy. In the dosimetric phase, subjects will receive one 5 mCi dose of the study drug and undergo whole body imaging on on the day of infusion and on post-infusion days 1, 2, 3, and 6 for assessment of biodistribution of I-131-CLR1404. If normal and expected biodistribution are demonstrated, the subject will begin the therapy phase. In the therapy phase, the first cohort of subjects will receive a dose of 12.5 mCi/m2. Dose escalation in subsequent cohorts will initially be in increments of 12.5 mCi/m2. Subjects will be followed and observed for unacceptable toxicity through 56 days after the therapy dose infusion with follow-up for up to one year. All subjects will be prescribed thyroid protection medication to be taken 24 hours prior to injection of the dosimetric dose, and continuing for 14 days after the administration of the therapy dose.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Description: * Dosimetry: IV, 5 mCi, single dose, 6-day duration * Therapy: IV, starting dose level of 12.5 mCi/m2, single dose, 56-day duration with follow up to one year
City of Hope National Medical Center
Duarte, California, United States
Georgetown University Hospital
Washington D.C., District of Columbia, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Determination of the recommended dose of I-131-CLR1404 in treating subjects with relapsed or refractory advanced solid malignancies
Largest administered dose with at most a 20% dose limiting toxicity rate
Time frame: Until non-tolerated dose is defined; dose escalation descision made upon review of data from a complete cohort (56 days after all subjects in cohort have received therapy infusion)
Expansion of the safety profile of I-131-CLR1404
Assesment by physical examination, vital signs, ECG, laboratory changes over time, and adverse events
Time frame: Pre-infusion and 6 days after dosimetry infusion; weekly until 56 days after therapy infusion and then monthly for one year
Expansion of the pharmacokinetic profile of I-131-CLR1404
Determination of the following pharmacokinetic parameters of I-131-CLR1404: * Area under the plasma concentration versus time curve (AUC) * Maximum (peak) plasma concentration (Cmax) * Time required to reduce the plasma concentration to one half its initial value (t1/2) * Volume of distribution (Vd) * Clearance of the drug from plasma (Cl)
Time frame: Pre-infusion and 144 hours post-dosimetry infusion; pre-infusion, 5, 15, 60 minutes, 5, 24, 72 hours, 6, 14, 21, 28, 35, 42, 49 and 56 days post-therapy infusion
Preliminary antitumor activity of I-131-CLR1404
CT imaging (response and progression will be evaluated using RECIST 1.1) and tumor marker evaluation in subjects with applicable tumors (performed at screening, 28 and 56 days post-therapy infusion)
Time frame: Baseline at screening, 56 days post-therapy infusion, every 2 months in follow-up period up to one year
Tumor dosimetry of I-131-CLR1404 in a subset of subjects with non-hepatic lesions measuring at least 2 cm in one dimension
SPECT or SPECT/CT
Time frame: 72 hours, 6, 14, and 21 days post-therapy infusion
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