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IV dose of CLR 131, increased/decreased by dose level; single or fractionated dose

CLR 131

Jarrod Longcor

The study evaluates CLR 131 in children, adolescents, and young adults with relapsed or refractory malignant solid tumors and lymphoma and recurrent or refractory malignant brain tumors for which there are no standard treatment options with curative potential.

Even with standard, highly toxic multimodality therapies and salvage regimen, most pediatric patients with primary metastatic or relapsed solid tumors are confronted with a poor prognosis. For these patients there is currently no accepted successful treatment regimen. There is a need for new drugs, including targeted radiopharmaceuticals, preferably with cancer-specific uptake and broad applicability for these rare pediatric malignancies.

CLR 131 is a radioiodinated therapeutic that exploits the selective uptake and retention of phospholipid ethers (PLEs) by malignant cells. Cellectar Biosciences' novel cancer-targeted small-molecule compound (CLR1404) is radiolabeled with the isotope iodine-131 (I-131). CLR 131 has demonstrated tumor selective uptake across numerous adult and pediatric cancer cell types. Therapeutic efficacy has been demonstrated in various pediatric and adult-type cancer xenograft models, confirming the ability of CLR 131 to target tumors.

Based on the critical unmet medical need for effective agents with novel mechanisms of action in relapsed pediatric cancers and initial preclinical and clinical experience with radioiodinated CLR1404, Cellectar Biosciences has chosen to assess CLR 131 in a phase 1 pediatric trial.

Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma

An Open-Label, Dose Escalation, Efficacy, and Safety Study of CLR 131 in Children, Adolescents, and Young Adults With Select Solid Tumors, Lymphoma, and Malignant Brain Tumors

DLT will be assessed by physical examination, vital signs, and laboratory values

Dose and regimen to be used in Phase 2 trials of CLR 131 in children, adolescents, and young adults

Response assessment per applicable criteria (e.g., Neuroblastoma Response Criteria (modified); RECIST 1.1; positron emission tomography response criteria in solid tumors (PERCIST); RANO)

Assessment via 131-I/CLR 131 SPECT/CT scans

Time from first infusion of CLR 131 until progression or recurrence of disease

Time from first infusion of CLR 131 until death due to any reason

Assessment of dosimetry via whole body planar imaging

Cellectar Biosciences, Inc.

Two dosing cohorts will be explored; patients in the first arm will receive two doses, 20 mCi/m2 each, separated by 14 days for two cycles, with a third optional cycle. Patients in the second arm will receive two doses, 10 mCi/m2 each, separated by 14 days for three cycles with a fourth optional cycle.

CLR 131 will be administered IV (intravenously) at a dose based on patients' BSA

Kate Oliver

Allison Pribnow, MD

Julia Glade-Blender, MD

Joseph Pressey, MD

Cassie Kline, MD

Ashley Bui, MD

Jennifer Foster, MD

Nicolas Pytel, MD

Daniel Morgenstern, MD

The purpose of this dose finding study is to evaluate the safety and efficacy of 2 different dose levels of CLR 131 in children, adolescents and young adults with relapsed or refractory high-grade glioma (HGG).

This study is designed to further evaluate the safety and tolerability of CLR 131 at the selected doses in children, adolescents and young adults with relapsed or refractory malignant high-grade glioma. It will also determine the therapeutic activity defined as progression free survival and overall survival, antitumor activity (treatment response) defined as the reduction in tumor volume and identify the recommended Phase 2/3 dose of CLR 131 in children, adolescents and young adults with relapsed or refractory HGG.

Drug: CLR 131 is a radio-iodinated therapy comprising a core phospholipid ether (PLE) analogue radiolabeled with iodine-131. CLR 131 exploits the tumor-targeting properties of PLEs to provide targeted delivery of radiation to malignant tumor cells and minimizes radiation exposure to normal tissues.

Novel Targeted Radiotherapy in Pediatric Patients With Inoperable Relapsed or Refractory HGG

A Phase 1b, Open-Label, Study of a Novel Targeted Radiotherapy in Children, Adolescents and Young Adults With Inoperable Relapsed or Refractory High-Grade Glioma

The IPD will be made available upon request of NCI, the funding agency partner. This has not yet been decided.

Will be assessed by physical examination, performance status, vital signs, laboratory changes over time, and adverse events. Evaluations will use a nonparametric Wilcoxon Signed Rank test and a linear mixed effects modeling will be conducted to evaluate longitudinal changes.

To determine the therapeutic activity defined as Progression Free Survival (PFS) using Kaplan Meier estimator. PFS is defined as the time from arm assignment until disease progression or death.

Determine antitumor activity (treatment response) defined as the reduction in tumor volume, measured by MRI scans acquired as FLAIR images and based on the RAPNO criteria for responses.

Identify the recommended Phase 2/3 dose of CLR 131 in relapsed pHGG patients based on both safety and efficacy assessments as defined by the primary endpoints concluded from this study.

To determine total body and organ dosimetry, together, of CLR 131 in relapsed pHGG patients, measured by conjugate planar whole-body imaging and/or blood collection drawn for radiologic dosimetry analysis for a subset of patients. Organ time/activity integrals will be entered into OLINDA/EXM software to produce total body and organ dosimetry values for CLR 131.

Determine the tumor uptake of CLR 131 and utility of SPECT/CT as a potential diagnostic for response. Images will be reconstructed using quantitative SPECT reconstruction methods with compensation for attenuation, scatter and the full collimator-detector response including septal penetration and scatter. A registered CT image will be used as the attenuation map for the SPECT images. Image data will be converted to activity per cubic centimeters using a sensitivity measurement made using a point source in air.

National Cancer Institute (NCI)

Head and Neck Neoplasms

All Drugs and Chemicals

Radiopharmaceuticals

Enrollment will start at dose level 1 (first 4 participants). Participants will receive 2 doses of CLR 131 intravenously with the first dose on day 1 followed by the second dose on day 8.

Dose Level -1 (de-escalation dose, if toxicities warrant) = 12.5 mCi/m\^2 Dose Level 1 (beginning dose) = 15.6 mCi/m\^2 Dose Level 2 (escalation dose) = 18.75 mCi/m\^2

Dose escalation will proceed with no limiting toxicities at each level (maximum of 8 participants at each dose level). With maximum tolerated dose confirmed, an expansion phase will proceed.

CLR 131 is a radiopharmaceutical dosed intravenously over a period of approximately 30 minutes, dose will be based on total body surface area calculated from actual body weight and height

Justine Bruce, MD

This is a Phase 1 study of the use of an investigational drug that selectively delivers radiation to malignant tumor cells, CLR 131, in combination with external beam radiation therapy (EBRT) in subjects with locoregionally recurrent head and neck cancer. The trial will enroll up to 12 participants who are amenable to retreatment with radiation therapy. Participants who also have distant metastatic disease may be enrolled on this clinical trial, but they must have evaluable disease that will be clinically treated with radiation therapy, as per standard of care. All participants will receive a dosimetry test dose of CLR 131 to establish drug uptake by the tumor and enable Monte Carlo dose estimation based on CLR 131 SPECT/CT imaging evaluation. Participants showing uptake will receive a cumulative tumor dose of 60-70 Gy using personalized dose calculation (via Monte Carlo methods) of CLR 131 combined with external beam radiation.

Following informed consent, all participants will receive a dosimetry test dose of 15 mCi CLR 131 to establish drug uptake by the tumor and enable Monte Carlo dose estimation based on CLR 131 SPECT/CT imaging evaluation.

Participants who have uptake of the CLR 131 dosimetry test dose at their disease site as determined by the study radiologist will be eligible to participate on the treatment portion of this clinical trial. Participants showing uptake will receive a cumulative tumor dose of 60-70 Gy using personalized dose calculation of CLR 131 (via Monte Carlo) combined with external beam radiation. In this study, we are also studying a subset of up to 6 patients who do not uptake after the CLR 131 test dose, who will still proceed with treatment with CLR 131.

This clinical trial involves two cohorts of subjects: (a) dose escalation and (b) dose expansion. In the dose escalation phase, an mTPI-2 design, an extension of modified toxicity probability interval (mTPI-2), will be used to identify the maximum tolerated dose (MTD) using cohorts of 4 participants and up to 3 dose levels of CLR 131. Participants in the dose escalation phase will receive 2 doses of CLR 131 with the first dose on day 1 followed by the second dose on day 8.

Treatment with CLR 131 on the dose escalation cohort will begin at dose level 1 (15.6 mCi/m2). Participants at dose level 1 will receive an intravenous infusion of CLR 131 at 15.6 mCi/m2 on day 1 followed by a second dose on day 8. Participants at dose level 2 will receive an intravenous infusion of CLR 131 at 18.75 mCi/m2 on day 1 followed by a second dose on day 8.

Once the MTD is determined by the dose escalation phase, participants will be enrolled on the dose expansion cohort. Participants on the dose expansion cohort will receive 2 doses of CLR 131 with the first dose on day 1 followed by the second dose on day 8, with the dose determined by the dose escalation phase.

SPECT/CT imaging will be performed on days 2, 3, 4-6, and 7-8 of the treatment period to visualize and quantitate the biodistribution of CLR 131. Based on these SPECT/CT imaging scans, the Bednarz lab will utilize the Monte Carlo method to predict absorbed dose of CLR 131 to tumors and normal structures.

All participants will start thyroid-protection medication the day prior to the CLR 131 dosimetry test dose and will continue to take thyroid protection medication for 14 days after the last CLR 131 dose.

Based on the calculated absorbed dose of CLR 131 to the specific targeted tissue, the participant will undergo external beam radiation therapy (EBRT) to complete the designated radiation dose outlined in the re-irradiation plan, as per standard of care. Prior to CLR 131 administration and at 3 and 6 months post EBRT, participants will be assessed for changes to swallow function. Prior to CLR 131 administration and at 3, 6 and 12 months post EBRT, quality of life measures and salivary characteristics will be assessed. The investigators anticipate the total study (baseline, CLR 131 administration, EBRT and 3, 6, 12 and 24 month follow up assessments) to take 27 months per participant.

Single center, dose escalation and dose expansion study

CLR 131 Combined With Radiation for Head and Neck Cancer

Therapeutic Combination of CLR 131 With External Beam Radiation in Head and Neck Cancer

Incidence of adverse events assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Investigators will use SPECT/CT imaging scans to predict the adsorbed dose of CLR 131 to tumors with the Monte Carlo method.

ORR defined as the proportion of subjects who experience either a partial response or complete response within 6 months post completion of EBRT as measured by standard of care imaging (e.g. CT, MR, PET-MR).

Swallow function assessed by Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale before and after treatment. The DIGEST scale cross references a clinician determined 'safety' grade with an 'efficiency' grade for an overall score between 0-4 where 0 is asymptomatic and 4 is life threatening.

Quality of life assessed by MD Anderson Dysphagia Inventory score (MDADI) before and after treatment. MDADI is a 36-item self-assessment with global, emotional, functional, and physical sub-scales. Total possible composite score range is 20-100 where 20 is extremely low functioning and 100 is high functioning.

Change in Stimulated Salivary Flow before and after treatment (mL/min).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma	NCT03478462	Pediatric Solid... Pediatric Lymph... Pediatric Brain... DIPG Neuroblastoma Ewing Sarcoma Rhabdomyosarcom... Osteosarcoma	CLR 131	2 Years - 25 Years	Cellectar Biosciences, Inc.
Novel Targeted Radiotherapy in Pediatric Patients With Inoperable Relapsed or Refractory HGG	NCT05610891	High-Grade Glio...	CLR 131	10 Years - 25 Years	Cellectar Biosciences, Inc.
CLR 131 Combined With Radiation for Head and Neck Cancer	NCT04105543	Head and Neck C...	CLR 131	18 Years -	University of Wisconsin, Madison
CLR 131 Combined With Radiation for Head and Neck Cancer	NCT04105543	Head and Neck C...	CLR 131	18 Years -	University of Wisconsin, Madison

Spots Global Cancer Trial Database for clr 131

Every month we try and update this database with for clr 131 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for clr 131

Every month we try and update this database with for clr 131 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for clr 131 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.