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Head and Neck CancerPhase 1NCT04105543

CLR 131 Combined With Radiation for Head and Neck Cancer

A Phase 1 study testing CLR 131 in people with Head and Neck Cancer, run by University of Wisconsin, Madison at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Cancer
What is being tested?
CLR 131
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
2 sitesUnited States
Study dates
20 Dec 2019to 1 Feb 2024
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • serum creatinine ≤ 1.5 times the upper limit of normal (ULN) or Cockcroft-Gault calculated creatinine clearance >/= 60 ml/min
  • The participant has adequate hepatic function as defined by:
  • total bilirubin ≤ 1.5 mg/dL (25.65 μmol/L)
  • aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times the ULN
  • Women of childbearing potential (WOCP) have a confirmed negative urine pregnancy test within 24 hours prior to test dose of CLR 131.
  • Participants must use a medically acceptable method of birth control such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence during the study participation and for 6 months after last dose of study drug. Women who are postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) are not considered to be WOCP.
  • Men who are not surgically or medically sterile agree to use an acceptable method of contraception. Male participants with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must abstain from intercourse for three weeks after each CLR 131 dose and agree to use condoms at least 6 months after the last dose of study drug. Total abstinence for the same study period is an acceptable alternative.

Who cannot join

  • 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.
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  • 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
  • Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry
  • History of myocardial infarction, ventricular arrhythmia, stable/unstable angina, symptomatic congestive heart failure, coronary/peripheral artery bypass graft or stenting or other significant cardiac disease within 6 months prior to study entry
  • QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥480 ms.
  • Any condition requiring the use of immunosuppression, excluding rheumatologic conditions treated with stable doses of corticosteroids (equivalent to £ prednisone 10 mg daily)
  • Ongoing hemodialysis or peritoneal dialysis
  • Poorly controlled severe Chronic Obstructive Pulmonary Disease (COPD)
  • Uncontrolled hypothyroidism or hyperthyroidism
  • Any medical condition that predisposes the subject to uncontrolled bleeding such as hemophilia, factor deficiencies, severe liver disease, or von Willebrand disease.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • UW Cancer Center Johnson Creek

    Johnson Creek, Wisconsin, 53038

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

Other trials in United States

About this study

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

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.

Read the detailed description

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.

Being tested
CLR 131
Medical subject headings
Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CLR 131Drug

    Also called I-131-CLR1404

    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

Study groups in NCT04105543
Study groupRoleWhat they receive
CLR 131 Dose EscalationExperimentalEnrollment 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.
Receives: Drug: CLR 131

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: up to 18 weeks

  2. Summary of Adverse Events Possibly Related to Treatment

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

    Measured: up to 18 weeks

Secondary outcomes (11)

  1. CLR 131 Tumor Uptake Via SPECT/CT Imaging

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

    Measured: Up to 8 days

  2. Median Radiation Treatment Time

    Measured: up to 14 weeks

  3. Number of Dose Delays

    Measured: up to 14 weeks

  4. Response Rates

    Complete response (CR), disappearance of all tumors; Partial response (PR), at least 30% decrease in the sum of the longest diameter of target tumors; Stable disease (SD), no increase or decrease to tumor size; Progressive disease (PD), increasing tumor size. RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.

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

  5. Overall Response Rate (ORR)

    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).

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

  6. Swallow Function: DIGEST Scale

    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. Data collected at baseline, 3 months, and 6 months post completion of external beam radiation therapy (EBRT).

    Measured: up to 6 months post completion of EBRT (up to 9 months on study)

  7. Quality of Life: MDADI Score

    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. Data collected at baseline, 3 months, and 6 months, and 12 months post EBRT.

    Measured: Assessed at 3 months and 6 months post EBRT (6 months and 9 months post-baseline). Originally pre-specified to be assessed at 12 months post EBRT, data not collected

  8. Stimulated Salivary Flow

    Stimulated Salivary Flow before and after treatment (mL/min). Data collected at baseline, 3 months, and 6 months post EBRT.

    Measured: up to 6 months post completion of EBRT (up to 9 months on study)

  9. EORTC QLQ-C30 Scores

    The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) is a 30-item instrument measures quality of life in cancer patients. It is scored from 0-100 where higher scores indicate higher level of response in function, symptomatology, or global health.

    Measured: up to 6 months post completion of EBRT (up to 9 months on study)

  10. Xerostomia Quality-of-Life Scale (XeQoLS) Scores

    The XeQoLS questionnaire measures the effects of xerostomia on oral health-related quality of life. The questionnaire consists of 15 items, each rated on a 0-to-4 point Likert scale, for a total possible range of scores from 0 to 60, with higher scores indicating more severe symptom burden.

    Measured: up to 6 months post completion of EBRT (up to 9 months on study)

  11. Xerostomia Inventory Score

    The Xerostomia Inventory is an 11-item survey scored on a 5 point-likert scale (never, hardly ever, occasionally, fairly often, very much). Total possible range of scores is from 11-55, with higher scores indicating increased mouth dryness.

    Measured: up to 6 months post completion of EBRT (up to 9 months on study)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2019
  2. Study start20 Dec 2019
  3. Primary completion19 Sep 2022
  4. Study completion1 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single center, dose escalation and dose expansion study
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04105543
Sponsor's protocol ID
UW19041
Other IDs
P50DE026787, 2019-0681, A534260, SMPH/MEDICINE/HEM-ONC, NCI-2019-05419, Protocol Version 11/9/2021
Status last verified
Jul 2024
First submitted
25 Sep 2019
Last updated
2 Sep 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39671752

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CLR 131 in people with Head and Neck Cancer, run by University of Wisconsin, Madison at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Treatment Related Adverse Events (time frame: up to 18 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04105543, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2025.

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