- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04105543
CLR 131 Combined With Radiation for Head and Neck Cancer
Therapeutic Combination of CLR 131 With External Beam Radiation in Head and Neck Cancer
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Wisconsin
-
Johnson Creek, Wisconsin, United States, 53038
- UW Cancer Center Johnson Creek
-
Madison, Wisconsin, United States, 53792
- University of Wisconsin Carbone Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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:
- 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.
Exclusion Criteria:
- 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
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CLR 131 Dose Escalation
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
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Adverse Events
Time Frame: up to 18 weeks
|
Incidence of adverse events assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
|
up to 18 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
CLR 131 Tumor Uptake via SPECT/CT Imaging
Time Frame: Up to 8 days
|
Investigators will use SPECT/CT imaging scans to predict the adsorbed dose of CLR 131 to tumors with the Monte Carlo method.
|
Up to 8 days
|
Median Radiation Treatment Time
Time Frame: up to 14 weeks
|
up to 14 weeks
|
|
Median Number of Dose Delays Due to Toxicity
Time Frame: up to 14 weeks
|
up to 14 weeks
|
|
Overall Response Rate (ORR)
Time Frame: up to 9 months
|
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).
|
up to 9 months
|
Change in Swallow Function: DIGEST Scale
Time Frame: up to 9 months
|
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.
|
up to 9 months
|
Change in Quality of Life: MDADI Score
Time Frame: up to 15 months
|
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.
|
up to 15 months
|
Change in Stimulated Salivary Flow
Time Frame: up to 9 months
|
Change in Stimulated Salivary Flow before and after treatment (mL/min).
|
up to 9 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Justine Bruce, MD, University of Wisconsin, Madison
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- UW19041
- A534260 (Other Identifier: UW Madison)
- SMPH/MEDICINE/HEM-ONC (Other Identifier: UW Madison)
- P50DE026787 (U.S. NIH Grant/Contract)
- 2019-0681 (Other Identifier: Institutional Review Board)
- NCI-2019-05419 (Registry Identifier: NCI Trial ID)
- Protocol Version 11/9/2021 (Other Identifier: UW Madison)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Head and Neck Cancer
-
Robert FerrisAmgenCompletedHead and Neck Cancer | Cancer of Head and Neck | Head Cancer | Neck Cancer | Neoplasms, Head and Neck | Cancer of the Head and Neck | Cancer of Neck | Upper Aerodigestive Tract Neoplasms | Neck Neoplasms | Cancer of the Head | Cancer of the Neck | UADT Neoplasms | Cancer of Head | Head Neoplasms | Head, Neck Neoplasms | Neoplasms, Head and other conditionsUnited States
-
Assiut UniversityRecruitingHead and Neck Cancer | Head and Neck Neoplasms | Cancer of Head and Neck | Neoplasms, Head and Neck | Cancer of the Head and NeckEgypt
-
Mayo ClinicRecruitingCancer Head Neck | Cancer Neck | Cancer, HeadUnited States
-
IRCCS Policlinico S. MatteoNestlé Health Science Spain; Akern SrlCompletedHead-neck CancerItaly
-
University of California, San FranciscoCompleted
-
Chinook Therapeutics, Inc. (formerly Aduro)TerminatedRecurrent Head and Neck Cancer | Metastatic Head and Neck CancerUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)TerminatedHead And Neck CancerUnited States
-
National Cancer Institute (NCI)TerminatedRecurrent Head and Neck Cancer | Metastatic Head and Neck CancerUnited States
-
Radboud University Medical CenterUnknown
-
Centre Oscar LambretUnknownEpidermoid Head and Neck CancerFrance
Clinical Trials on CLR 131
-
Cellectar Biosciences, Inc.National Cancer Institute (NCI)RecruitingHigh-Grade GliomaUnited States, Canada
-
Cellectar Biosciences, Inc.Active, not recruitingOsteosarcoma | Ewing Sarcoma | Neuroblastoma | Rhabdomyosarcoma | Pediatric Brain Tumor | DIPG | Pediatric Solid Tumor | Pediatric LymphomaUnited States, Australia, Canada
-
Cellectar Biosciences, Inc.RecruitingMultiple Myeloma | Waldenstrom Macroglobulinemia | Mantle Cell Lymphoma | Marginal Zone Lymphoma | Chronic Lymphocytic Leukemia | Lymphoplasmacytic Lymphoma | Diffuse Large B Cell Lymphoma | Small Lymphocytic Lymphoma | Central Nervous System LymphomaUnited States, Australia, Czechia, Greece, Israel, Brazil, Finland, France, Spain, Turkey, United Kingdom
-
BledinaSuspendedInterest of Biofer ® Compound Used in Blédilait Follow on Milk in Infant With Latent Iron DeficiencyLatent Iron DeficiencyFrance
-
Cellectar Biosciences, Inc.CompletedMultiple MyelomaUnited States
-
Stealth BioTherapeutics Inc.ICON Clinical ResearchCompletedReperfusion Injury | STEMIUnited States, Hungary, Germany, Poland
-
Case Comprehensive Cancer CenterCompletedHead and Neck Cancer | Head and Neck Squamous Cell CarcinomaUnited States
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)Active, not recruitingRecurrent Thyroid Gland Carcinoma | Poorly Differentiated Thyroid Gland Carcinoma | Stage IV Thyroid Gland Follicular Carcinoma AJCC v7 | Stage IV Thyroid Gland Papillary Carcinoma AJCC v7 | Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7 | Stage IVA Thyroid Gland Papillary Carcinoma AJCC... and other conditionsUnited States
-
Kissei Pharmaceutical Co., Ltd.JCR Pharmaceuticals Co., Ltd.Completed
-
Stealth BioTherapeutics Inc.CompletedNormal and Impaired Renal FunctionUnited States