Head and Neck Cancer
Conditions
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.
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.
Interventions
DRUGCLR 131
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
Sponsors
National Institute of Dental and Craniofacial Research (NIDCR)
Cellectar Biosciences, Inc.
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single center, dose escalation and dose expansion study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Related Adverse Events | up to 18 weeks | 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) |
| Summary of Adverse Events Possibly Related to Treatment | up to 18 weeks | Adverse Events Grading (1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, and 5 = death) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Dose Delays | up to 14 weeks | — |
| Response Rates | 6 months post completion of EBRT, up to 9 months on study | 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. |
| Overall Response Rate (ORR) | 6 months post completion of EBRT, up to 9 months on study | 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: DIGEST Scale | up to 6 months post completion of EBRT (up to 9 months on study) | 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). |
| CLR 131 Tumor Uptake Via SPECT/CT Imaging | 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. |
| Stimulated Salivary Flow | up to 6 months post completion of EBRT (up to 9 months on study) | Stimulated Salivary Flow before and after treatment (mL/min). Data collected at baseline, 3 months, and 6 months post EBRT. |
| EORTC QLQ-C30 Scores | up to 6 months post completion of EBRT (up to 9 months on study) | 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. |
| Xerostomia Quality-of-Life Scale (XeQoLS) Scores | up to 6 months post completion of EBRT (up to 9 months on study) | 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. |
| Xerostomia Inventory Score | up to 6 months post completion of EBRT (up to 9 months on study) | 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. |
| Quality of Life: MDADI Score | 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 | 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. |
| Median Radiation Treatment Time | up to 14 weeks | — |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled from October 2020 to February 2022 at the UW Hospital and Clinics.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | CLR 131 Dose Escalation |
|---|---|
| Age, Continuous | 65.5 years |
| Age, Customized 40-49 years | 2 Participants |
| Age, Customized 50-59 years | 3 Participants |
| Age, Customized 60-69 years | 2 Participants |
| Age, Customized 70-79 years | 3 Participants |
| Age, Customized 80-89 years | 2 Participants |
| AJCC 8th ed. stage Stage I | 2 Participants |
| AJCC 8th ed. stage Stage II | 3 Participants |
| AJCC 8th ed. stage Stage III | 3 Participants |
| AJCC 8th ed. stage Stage IVA | 2 Participants |
| AJCC 8th ed. stage Stage IVB | 2 Participants |
| ECOG Performance Status ECOG 0 | 9 Participants |
| ECOG Performance Status ECOG 1 | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Initial Treatment at Diagnosis Definitive Chemoradiation | 5 Participants |
| Initial Treatment at Diagnosis Surgical Resection: Adjuvant chemoradiation | 2 Participants |
| Initial Treatment at Diagnosis Surgical Resection: Adjuvant radiation | 4 Participants |
| Initial Treatment at Diagnosis Surgical Resection: No adjuvant treatment | 1 Participants |
| N stage N0 and N1 | 6 Participants |
| N stage N2 and N3 | 6 Participants |
| Primary Tumor Site Larynx | 1 Participants |
| Primary Tumor Site Nasopharynx | 1 Participants |
| Primary Tumor Site Oral cavity | 4 Participants |
| Primary Tumor Site Oropharynx | 5 Participants |
| Primary Tumor Site Salivary Gland | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Recurrence Status at Study Entry First Recurrence | 6 Participants |
| Recurrence Status at Study Entry Metastatic Disease | 1 Participants |
| Recurrence Status at Study Entry Multiply Recurrent | 6 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 9 Participants |
| T stage T1 and T2 | 6 Participants |
| T stage T3 and T4 | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 12 |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 4 / 12 |
Outcome results
Primary
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)
Time frame: up to 18 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CLR 131 | Incidence of Treatment Related Adverse Events | Blood and lymphatic system disorders: Anemia | 4 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Investigations: White blood cell decreased | 0 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Investigations: Lymphocyte count decreased | 0 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Dysphagia | 0 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Investigations: Neutrophil count decreased | 0 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Investigations: Weight loss | 0 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Investigations: Platelet count decreased | 1 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Blood and lymphatic system disorders: Febrile neutropenia | 0 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Investigations: Thyroid stimulating hormone increased | 1 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Nervous system disorders: Headache | 1 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Mucositis oral | 1 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Nausea | 0 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Nervous system disorders: Dysgeusia | 1 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Salivary Duct Inflammation | 1 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Respiratory, thoracic and mediastinal disorders: Oropharyngeal pain | 2 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | General disorders: Fatigue | 4 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Dry mouth | 2 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Musculoskeletal and connective tissue disorders: Fibrosis deep connective tissue | 1 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | General disorders: Fever | 1 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | General disorders: Pain | 0 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Metabolism and nutrition disorders: Anorexia | 1 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Infections and infestations: Thrush | 0 Participants |
| CLR 131 | Incidence of Treatment Related Adverse Events | Injury, poisoning and procedural complications: Dermatitis Radiation | 1 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Metabolism and nutrition disorders: Anorexia | 1 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Nervous system disorders: Headache | 0 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Salivary Duct Inflammation | 0 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Investigations: Lymphocyte count decreased | 0 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | General disorders: Pain | 1 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Investigations: Weight loss | 2 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Musculoskeletal and connective tissue disorders: Fibrosis deep connective tissue | 0 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Investigations: Neutrophil count decreased | 1 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Dysphagia | 2 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Respiratory, thoracic and mediastinal disorders: Oropharyngeal pain | 0 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | General disorders: Fatigue | 2 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Investigations: Platelet count decreased | 1 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Investigations: White blood cell decreased | 2 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Investigations: Thyroid stimulating hormone increased | 0 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Injury, poisoning and procedural complications: Dermatitis Radiation | 0 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Infections and infestations: Thrush | 1 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | General disorders: Fever | 0 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Mucositis oral | 0 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Blood and lymphatic system disorders: Febrile neutropenia | 0 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Nervous system disorders: Dysgeusia | 0 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Dry mouth | 1 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Nausea | 1 Participants |
| DIGEST Safety Grade | Incidence of Treatment Related Adverse Events | Blood and lymphatic system disorders: Anemia | 2 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Injury, poisoning and procedural complications: Dermatitis Radiation | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Blood and lymphatic system disorders: Anemia | 4 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Blood and lymphatic system disorders: Febrile neutropenia | 2 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Dry mouth | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Dysphagia | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Mucositis oral | 1 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Nausea | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Salivary Duct Inflammation | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | General disorders: Fatigue | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | General disorders: Fever | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | General disorders: Pain | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Infections and infestations: Thrush | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Investigations: Lymphocyte count decreased | 5 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Investigations: Neutrophil count decreased | 1 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Investigations: Platelet count decreased | 3 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Investigations: Thyroid stimulating hormone increased | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Investigations: Weight loss | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Investigations: White blood cell decreased | 2 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Metabolism and nutrition disorders: Anorexia | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Musculoskeletal and connective tissue disorders: Fibrosis deep connective tissue | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Nervous system disorders: Dysgeusia | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Nervous system disorders: Headache | 0 Participants |
| DIGEST Efficacy Grade | Incidence of Treatment Related Adverse Events | Respiratory, thoracic and mediastinal disorders: Oropharyngeal pain | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Infections and infestations: Thrush | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Respiratory, thoracic and mediastinal disorders: Oropharyngeal pain | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Investigations: White blood cell decreased | 7 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | General disorders: Pain | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | General disorders: Fever | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Nervous system disorders: Headache | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Metabolism and nutrition disorders: Anorexia | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | General disorders: Fatigue | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Salivary Duct Inflammation | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Blood and lymphatic system disorders: Febrile neutropenia | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Musculoskeletal and connective tissue disorders: Fibrosis deep connective tissue | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Nausea | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Mucositis oral | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Blood and lymphatic system disorders: Anemia | 1 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Nervous system disorders: Dysgeusia | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Investigations: Platelet count decreased | 6 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Dysphagia | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Investigations: Thyroid stimulating hormone increased | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Investigations: Neutrophil count decreased | 7 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Investigations: Lymphocyte count decreased | 4 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Gastrointestinal disorders: Dry mouth | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Investigations: Weight loss | 0 Participants |
| Grade 4 | Incidence of Treatment Related Adverse Events | Injury, poisoning and procedural complications: Dermatitis Radiation | 0 Participants |
Primary
Summary of Adverse Events Possibly Related to Treatment
Adverse Events Grading (1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, and 5 = death)
Time frame: up to 18 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CLR 131 | Summary of Adverse Events Possibly Related to Treatment | Leukopenia | 11 Participants |
| CLR 131 | Summary of Adverse Events Possibly Related to Treatment | Pain, Oral and Oropharyngeal | 3 Participants |
| CLR 131 | Summary of Adverse Events Possibly Related to Treatment | Neutropenia | 9 Participants |
| CLR 131 | Summary of Adverse Events Possibly Related to Treatment | Febrile neutropenia | 2 Participants |
| CLR 131 | Summary of Adverse Events Possibly Related to Treatment | Thrombocytopenia | 11 Participants |
| CLR 131 | Summary of Adverse Events Possibly Related to Treatment | Mucositis oral | 2 Participants |
| CLR 131 | Summary of Adverse Events Possibly Related to Treatment | Anemia | 11 Participants |
| CLR 131 | Summary of Adverse Events Possibly Related to Treatment | Anorexia | 2 Participants |
| CLR 131 | Summary of Adverse Events Possibly Related to Treatment | Lymphopenia | 9 Participants |
| CLR 131 | Summary of Adverse Events Possibly Related to Treatment | Dysphagia | 2 Participants |
| CLR 131 | Summary of Adverse Events Possibly Related to Treatment | Fatigue | 6 Participants |
| CLR 131 | Summary of Adverse Events Possibly Related to Treatment | Weight loss | 2 Participants |
| CLR 131 | Summary of Adverse Events Possibly Related to Treatment | Dry mouth | 3 Participants |
| DIGEST Safety Grade | Summary of Adverse Events Possibly Related to Treatment | Weight loss | 0 Participants |
| DIGEST Safety Grade | Summary of Adverse Events Possibly Related to Treatment | Thrombocytopenia | 9 Participants |
| DIGEST Safety Grade | Summary of Adverse Events Possibly Related to Treatment | Leukopenia | 9 Participants |
| DIGEST Safety Grade | Summary of Adverse Events Possibly Related to Treatment | Lymphopenia | 9 Participants |
| DIGEST Safety Grade | Summary of Adverse Events Possibly Related to Treatment | Neutropenia | 8 Participants |
| DIGEST Safety Grade | Summary of Adverse Events Possibly Related to Treatment | Anemia | 5 Participants |
| DIGEST Safety Grade | Summary of Adverse Events Possibly Related to Treatment | Dry mouth | 0 Participants |
| DIGEST Safety Grade | Summary of Adverse Events Possibly Related to Treatment | Pain, Oral and Oropharyngeal | 0 Participants |
| DIGEST Safety Grade | Summary of Adverse Events Possibly Related to Treatment | Febrile neutropenia | 2 Participants |
| DIGEST Safety Grade | Summary of Adverse Events Possibly Related to Treatment | Mucositis oral | 1 Participants |
| DIGEST Safety Grade | Summary of Adverse Events Possibly Related to Treatment | Anorexia | 0 Participants |
| DIGEST Safety Grade | Summary of Adverse Events Possibly Related to Treatment | Dysphagia | 0 Participants |
| DIGEST Safety Grade | Summary of Adverse Events Possibly Related to Treatment | Fatigue | 0 Participants |
Secondary
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.
Time frame: Up to 8 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CLR 131 | CLR 131 Tumor Uptake Via SPECT/CT Imaging | 6.23 gray (Gy) |
Secondary
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.
Time frame: up to 6 months post completion of EBRT (up to 9 months on study)
Population: Unable to collect data from all participants at all timepoints
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| CLR 131 | EORTC QLQ-C30 Scores | 3 months post EBRT | 72.2 score on a scale | Standard Deviation 13.1 |
| CLR 131 | EORTC QLQ-C30 Scores | baseline | 76.7 score on a scale | Standard Deviation 16.7 |
| CLR 131 | EORTC QLQ-C30 Scores | 6 months post EBRT | 71.1 score on a scale | Standard Deviation 11.2 |
| DIGEST Safety Grade | EORTC QLQ-C30 Scores | 3 months post EBRT | 26.92 score on a scale | Standard Deviation 12.28 |
| DIGEST Safety Grade | EORTC QLQ-C30 Scores | baseline | 23.08 score on a scale | Standard Deviation 17.92 |
| DIGEST Safety Grade | EORTC QLQ-C30 Scores | 6 months post EBRT | 28.21 score on a scale | Standard Deviation 19.39 |
| DIGEST Efficacy Grade | EORTC QLQ-C30 Scores | baseline | 50 score on a scale | Standard Deviation 13.82 |
| DIGEST Efficacy Grade | EORTC QLQ-C30 Scores | 6 months post EBRT | 58.3 score on a scale | Standard Deviation 15.59 |
| DIGEST Efficacy Grade | EORTC QLQ-C30 Scores | 3 months post EBRT | 54.2 score on a scale | Standard Deviation 19.32 |
Comparison: Wilcoxon Signed Rank Tests for EORTC QLQ-C30 Functional Score Baseline to 3 months (n=9)p-value: 0.21395% CI: [-14.4, 4.4]Wilcoxon Signed Rank Tests
Comparison: Wilcoxon Signed Rank Test for EORTC QLQ-C30 Functional Scores Baseline to 6 months (n=5)p-value: 0.68695% CI: [-17.8, 20]Wilcoxon Signed Rank Test
Comparison: Wilcoxon Signed Rank Tests for EORTC QLQ-C30 Symptom Score Baseline to 3 months (n=9)p-value: 0.49895% CI: [-0.769, 12.82]Wilcoxon Signed Rank Test
Comparison: Wilcoxon Signed Rank Test for EORTC QLQ-C30 Symptom Scores Baseline to 6 months (n=5)p-value: 0.41695% CI: [-15.39, 35.89]Wilcoxon Signed Rank Test
Comparison: Wilcoxon Signed Rank Tests for EORTC QLQ-C30 Global Health Status Score Baseline to 3 months (n=9)p-value: 0.77895% CI: [-20.84, 16.67]Wilcoxon Signed Rank Test
Comparison: Wilcoxon Signed Rank Test for EORTC QLQ-C30 Global Health Status Scores Baseline to 6 months (n=5)p-value: 0.8995% CI: [-25, 25]Wilcoxon Signed Rank Test
Secondary
Median Radiation Treatment Time
Time frame: up to 14 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CLR 131 | Median Radiation Treatment Time | 43 days |
Secondary
Number of Dose Delays
Time frame: up to 14 weeks
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| CLR 131 | Number of Dose Delays | Due to Toxicity | 0 doses |
| CLR 131 | Number of Dose Delays | Due to Production Difficulties | 1 doses |
Secondary
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).
Time frame: 6 months post completion of EBRT, up to 9 months on study
Population: One Participant did not undergo post treatment cross-sectional imaging and thus did not have any response data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CLR 131 | Overall Response Rate (ORR) | 8 Participants |
Secondary
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.
Time frame: 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
Population: Unable to collect data from all participants at all timepoints
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| CLR 131 | Quality of Life: MDADI Score | baseline | 71.6 score on a scale | Standard Deviation 15.9 |
| CLR 131 | Quality of Life: MDADI Score | 3 months post EBRT | 62.1 score on a scale | Standard Deviation 20.6 |
| CLR 131 | Quality of Life: MDADI Score | 6 months post EBRT | 55.8 score on a scale | Standard Deviation 7.68 |
Comparison: Wilcoxon Signed Rank Tests for MDADI Composite Baseline to 3 months (n=9)p-value: 0.17395% CI: [-12.64, 4.24]Wilcoxon Signed Rank Tests
Comparison: Wilcoxon Signed Rank Test for MDADI Composite Baseline to 6 months (n=5)p-value: 0.22595% CI: [-28.43, 7.39]Wilcoxon Signed Rank Test
Secondary
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.
Time frame: 6 months post completion of EBRT, up to 9 months on study
Population: One Participant did not undergo post treatment cross-sectional imaging and thus did not have any response data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CLR 131 | Response Rates | Complete Response | 7 Participants |
| CLR 131 | Response Rates | Partial Response | 1 Participants |
| CLR 131 | Response Rates | Stable Disease | 1 Participants |
| CLR 131 | Response Rates | Progressive Disease | 2 Participants |
Secondary
Stimulated Salivary Flow
Stimulated Salivary Flow before and after treatment (mL/min). Data collected at baseline, 3 months, and 6 months post EBRT.
Time frame: up to 6 months post completion of EBRT (up to 9 months on study)
Population: Unable to collect data from all participants at all timepoints
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| CLR 131 | Stimulated Salivary Flow | baseline | 0.24 ml/min | Standard Deviation 0.26 |
| CLR 131 | Stimulated Salivary Flow | 3 months post EBRT | 0.18 ml/min | Standard Deviation 0.1 |
| CLR 131 | Stimulated Salivary Flow | 6 months post EBRT | 0.21 ml/min | Standard Deviation 0.21 |
Comparison: Wilcoxon Signed Rank Tests for Stimulated Saliva Flow Baseline to 3 months (n=8)p-value: 0.77995% CI: [-0.246, 0.09]Wilcoxon Signed Rank Tests
Comparison: Wilcoxon Signed Rank Test for Stimulated Saliva Flow Baseline to 6 months (n=4)p-value: 0.46595% CI: [-0.218, 0.12]Wilcoxon Signed Rank Test
Secondary
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).
Time frame: up to 6 months post completion of EBRT (up to 9 months on study)
Population: Unable to collect data from all participants at all timepoints
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| CLR 131 | Swallow Function: DIGEST Scale | 3 months post EBRT | 2 score on a scale | Standard Deviation 1.3 |
| CLR 131 | Swallow Function: DIGEST Scale | baseline | 2 score on a scale | Standard Deviation 1.075 |
| CLR 131 | Swallow Function: DIGEST Scale | 6 months post EBRT | 3 score on a scale | Standard Deviation 1.3 |
| DIGEST Safety Grade | Swallow Function: DIGEST Scale | 3 months post EBRT | 1 score on a scale | Standard Deviation 0.928 |
| DIGEST Safety Grade | Swallow Function: DIGEST Scale | baseline | 1 score on a scale | Standard Deviation 0.9428 |
| DIGEST Safety Grade | Swallow Function: DIGEST Scale | 6 months post EBRT | 2 score on a scale | Standard Deviation 1.14 |
| DIGEST Efficacy Grade | Swallow Function: DIGEST Scale | baseline | 3 score on a scale | Standard Deviation 1.633 |
| DIGEST Efficacy Grade | Swallow Function: DIGEST Scale | 6 months post EBRT | 3 score on a scale | Standard Deviation 1.34 |
| DIGEST Efficacy Grade | Swallow Function: DIGEST Scale | 3 months post EBRT | 3 score on a scale | Standard Deviation 1.58 |
Secondary
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.
Time frame: up to 6 months post completion of EBRT (up to 9 months on study)
Population: Unable to collect data from all participants at all timepoints
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| CLR 131 | Xerostomia Inventory Score | baseline | 34.5 score on a scale | Standard Deviation 9.38 |
| CLR 131 | Xerostomia Inventory Score | 3 months post EBRT | 34.5 score on a scale | Standard Deviation 10.75 |
| CLR 131 | Xerostomia Inventory Score | 6 months post EBRT | 36.0 score on a scale | Standard Deviation 8.08 |
Comparison: Wilcoxon Signed Rank Tests for Xerostomia Inventory Baseline to 3 months (n=9)p-value: 0.67495% CI: [-3, 5]Wilcoxon Signed Rank Test
Comparison: Wilcoxon Signed Rank Test for Xerostomia Inventory Baseline to 6 months (n=5)p-value: 0.89295% CI: [-6, 6]Wilcoxon Signed Rank Test
Secondary
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.
Time frame: up to 6 months post completion of EBRT (up to 9 months on study)
Population: Unable to collect data from all participants at all timepoints
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| CLR 131 | Xerostomia Quality-of-Life Scale (XeQoLS) Scores | baseline | 15 score on a scale | Standard Deviation 14.4 |
| CLR 131 | Xerostomia Quality-of-Life Scale (XeQoLS) Scores | 3 months post EBRT | 16.5 score on a scale | Standard Deviation 16.9 |
| CLR 131 | Xerostomia Quality-of-Life Scale (XeQoLS) Scores | 6 months post EBRT | 18 score on a scale | Standard Deviation 13.1 |
Comparison: Wilcoxon Signed Rank Tests for XeQOL Baseline to 3 months (n=9)p-value: 0.13895% CI: [-2, 9.5]Wilcoxon Signed Rank Test
Comparison: Wilcoxon Signed Rank Test for XeQOL Baseline to 6 months (n=5)p-value: 0.22595% CI: [-10, 16]Wilcoxon Signed Rank Test