Clinical trial NCT05610891: Novel Targeted Radiotherapy in Pediatric Patients With Inoperable Relapsed or Refractory HGG
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: High-Grade Glioma
Lead sponsor: Cellectar Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2022-11-09
Enrollment: 50
Sex: ALL
Minimum age (years): 10
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Previously confirmed (histologically or cytologically) high grade glioma that is clinically or radiographically suspected to be relapsed, refractory, or recurrent
* ≥ 10 years of age and ≤ 25 years of age at time of consent/assent
* If ≥ age 16 years, Karnofsky performance status of ≥ 60. If \< age 16 years, Lansky performance status ≥ 60
* Platelets ≥ 75,000/μL (last transfusion, if any, must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
* Absolute neutrophil count ≥ 750/μL
* Hemoglobin ≥ 8 g/dL (last transfusion must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
* Using the bedside Schwartz formula, estimated GFR (creatinine clearance) \> 60 ml/min/1.73m2
* Alanine aminotransferase \< 3 × ULN
* Bilirubin \< 2 × ULN
* At least 1 measurable intracranial lesion with longest diameter of at least 10 mm on any imaging sequence.
* Patients with previously known neurological deficits must be clinically stable at time of enrollment and able to complete all study related procedures. Patients with documented or newly diagnosed neurological deficits will be enrolled at the investigator's discretion.
* If patient receives steroids for neurological symptom control, the dose must be stable (unchanged for three weeks prior to registration) or on a steroid tapering regimen. Initiation of steroids per routine care immediately prior to CLR 131 dosing is acceptable
* Patient or his or her legal representative is judged by the Investigator to have the initiative and means to be compliant with the protocol.
* Patient or his or her legal representative has the ability to read, understand, and provide written informed consent for the initiation of any study-related procedures.
* Female patients of childbearing potential must have a negative pregnancy test at screening and within 24 hours of dosing. It is recommended that female caregivers of childbearing potential have a negative pregnancy test within one week of dosing.
* Patients of childbearing potential must practice an effective method of birth control while participating on this study to avoid possible harm to the fetus.

Exclusion Criteria:

* Antitumor therapy or investigational therapy, within 3-half-lives of the agent preceding the present study. For certain types of radiation (craniospinal, total abdominal, whole lung \[spot irradiation to skull-based metastases is not considered craniospinal radiation for the purposes of this study\]), at least 3 months must have elapsed. Palliative focal radiation to non-target lesions should be completed at least 2 weeks prior to dosing. Patients participating in non-interventional clinical trials (i.e., non-drug) are allowed to participate in this trial
* History of hypersensitivity to thyroid protection medication (e.g., potassium iodide, Lugol's solution, etc.)
* Any other concomitant serious illness or organ system dysfunction (including cardiac and pulmonary dysfunction) that in the opinion of the Investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
* Major surgery within 6 weeks of enrollment unless delay in therapy poses unacceptable risk to the patient due to clinical progression (enrollment o such patients should be discussed with Medical Monitor)
* Known history of human immunodeficiency virus or uncontrolled, serious, active infection
* Pregnancy or breast-feeding

Primary outcomes:
measure: Safety Evaluation of CLR 131
timeFrame: Assessed throughout the study to 1-year post-infusion follow-up period
measure: Efficacy Evaluation for Progression Free Survival
timeFrame: Day 84 post-infusion follow-up period through 3 years following completion of treatment.
Secondary outcomes:
measure: Treatment Response of CLR 131
timeFrame: From date of arm assignment until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 48 months.
measure: Dose Determination for CLR 131
timeFrame: From date of arm assignment until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 48 months.
measure: Dosimetry Evaluation for Total Body and Organ
timeFrame: 4 hours post-infusion and concluding 4 weeks post-initial imaging
measure: Tumor Response to CLR 131
timeFrame: 4 hours post-infusion and concluding 4 weeks post-initial imaging
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Cancer Center, Baylor College of Medicine
state: Texas
city: Madison
country: United States
facility: University of Wisconsin, Carbone Cancer Center
state: Wisconsin
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Chief Operating Officer
name: Jarrod Longcor
role: STUDY_DIRECTOR
References: