CLR 131 Combined With Radiation for Head and Neck Cancer

NCT04105543 | Completed Phase 1 Results DMC FDA Drug

• 7 other identifiers: UW19041P50DE0267872019-0681A534260SMPH/MEDICINE/HEM-ONCNCI-2019-05419Protocol Version 11/9/2021
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Head and Neck Cancer

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment Related Adverse Events

  Incidence of adverse events assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse Events Grading (1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, and 5 = death)

  up to 18 weeks

• Summary of Adverse Events Possibly Related to Treatment

  Adverse Events Grading (1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, and 5 = death)

  up to 18 weeks

Secondary Outcomes (11)

• CLR 131 Tumor Uptake Via SPECT/CT Imaging

  Up to 8 days

• Median Radiation Treatment Time

  up to 14 weeks

• Number of Dose Delays

  up to 14 weeks

• Response Rates

  6 months post completion of EBRT, up to 9 months on study

• Overall Response Rate (ORR)

  6 months post completion of EBRT, up to 9 months on study

Study Arms (1)

CLR 131 Dose Escalation

EXPERIMENTAL

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.

Drug: CLR 131

Interventions

CLR 131 DRUG

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

Also known as: I-131-CLR1404

CLR 131 Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be informed of the investigational nature of the study and must be able to sign a written informed consent.
• Participants with histologically or cytologically confirmed solid malignancy that has recurred in the head and neck (above the clavicles) region, e.g., participants with recurrent cutaneous squamous cell carcinoma, salivary gland tumors or esthesioneuroblastoma are eligible for this clinical trial.
• Participants must have undergone previous curative intent therapy, with radiation as a primary or adjuvant therapy.
• Participants may have distant metastatic disease, as long as the locoregional site of recurrence is deemed eligible for radiation therapy, and treatment of the loco-regional disease is deemed as taking precedence over treatment of the remaining systemic disease.
• Participants must have at least one evaluable (measurable or non-measurable) recurrent lesion that is amenable to radiation therapy.
• Participants must demonstrate uptake of CLR 131 via SPECT/CT imaging, as determined by the study radiologist, in the specified site of recurrent/metastatic disease that is to be treated with radiation therapy. There is a subset of up to 6 patients who may continue with CLR 131 treatment without uptake on the SPECT/CT scan after the test dose.
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
• Participants must have a life expectancy of at least 6 months.
• The participant has adequate hematologic function, as evidenced by:
• an absolute neutrophil count (ANC) ≥ 1500 / µL
• hemoglobin ≥9 g/dL (5.58 mmol/L)
• and platelets ≥100,000 / µL
• If full-dose anticoagulation therapy is used, platelets ≥ 150,000 / µL are required.
• If participant is on full-dose anticoagulation therapy, the anticoagulation therapy must be reversible, and reversal of the anticoagulation therapy must not be life-threatening, as judged by the investigator.
• The participant has adequate renal function as defined by:

You may not qualify if:

• Recurrent tumor recommended for surgical resection based on multidisciplinary Head and Neck Oncology Tumor Board Review
• Thyroid cancer
• Known hypersensitivity to iodine
• Other concurrent severe and/or uncontrolled concomitant medical or psychiatric conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol, per investigator discretion
• Chemotherapy or major surgery within 4 weeks, or radiotherapy within 2 weeks prior to test dose of CLR 131.
• Participants with clinically significant adverse events due to agents administered more than 4 weeks prior to test dose of CLR 131 (alopecia and fatigue excluded). Clinical significance to be determined by investigator.
• The participant is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 6 months after the last dose of trial treatment.
• Any ongoing or active infection, including active tuberculosis, hepatitis B or C, or known infection with the human immunodeficiency virus (HIV)
• Concurrent treatment with any other anti-cancer or investigational agents. Participants cannot be receiving concomitant chemotherapy, radiotherapy, experimental therapy or any other therapy not otherwise outlined by the trial for the purposes of anti-cancer treatment.
• Participants with a history of or concurrent second primary malignancy (stage III or IV) within 5 years to study enrollment are excluded.
• Participants with a history of prior invasive malignancy (except early-stage I or II non-melanomatous skin cancer, carcinoma in situ of the breast, cervical carcinoma in situ, stage I-II papillary thyroid cancer, or low or very low-risk prostate cancer which has been completely treated with surgery or radiation) treated within 2 years of study enrollment are excluded.
• Participants that have had total body or hemibody irradiation, or have had prior systemic radioisotope therapy (except for benign thyroid disease)
• Poor venous access and will be unable to receive study drug into a peripheral venous catheter.
• Significant traumatic injury within 6 weeks prior to enrollment
• Extradural tumor in contact with the spinal cord or tumor located where swelling in response to therapy may impinge upon the spinal cord

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator
• Cellectar Biosciences, Inc.: collaborator

Study Sites (2)

UW Cancer Center Johnson Creek

Johnson Creek, Wisconsin, 53038, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Bruce JY, Burr A, Kimple RJ, Adam DP, Yu M, Piaskowski SM, Glazer TA, Hill P, Hartig GK, McCulloch TM, Wieland AM, Trask D, Oliver K, Longcor J, Rogus-Pulia N, Cho SY, Bednarz B, Harari PM. Safety and toxicity of Iopofosine I 131 (CLR 131) with external beam radiation therapy in recurrent or metastatic head and neck cancer: results of a phase 1 single-centre, open-label, single-arm, dose escalation and dose expansion study. EBioMedicine. 2025 Jan;111:105496. doi: 10.1016/j.ebiom.2024.105496. Epub 2024 Dec 12.

  PMID: 39671752 DERIVED

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

CLR1404

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Results Point of Contact

• Title: Justine Bruce, MD
• Organization: University of Wisconsin Carbone Cancer Center

jybruce@medicine.wisc.edu

(608) 262-4961

Study Officials

• Justine Bruce, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single center, dose escalation and dose expansion study

Study Record Dates

• First Submitted: September 25, 2019
• First Posted: September 26, 2019
• Study Start: December 20, 2019
• Primary Completion: September 19, 2022
• Study Completion: February 1, 2024
• Last Updated: September 2, 2025
• Results First Posted: August 15, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)