CLR 131 and External Beam Radiation Therapy for the Treatment of Patients with Recurrent Head and Neck Cancer

Inclusion Criteria

• Subject must be informed of the investigational nature of the study and must be able to sign a written informed consent
• Subjects with histologically or cytologically confirmed solid malignancy that has recurred in the head and neck (above the clavicles) region, e.g., subjects with recurrent cutaneous squamous cell carcinoma, salivary gland tumors or esthesioneuroblastoma are eligible for this clinical trial
• Subject is 18 years of age or older
• Subjects must have undergone previous curative intent therapy, with radiation as a primary or adjuvant therapy
• Subjects 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
• Subjects must have at least one evaluable (measurable or non-measurable) recurrent lesion that is amenable to radiation therapy
• Subjects must demonstrate uptake of CLR 131 via single photon emission computed tomography (SPECT)/computed tomography (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
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Subjects must have a life expectancy of at least 6 months
• An absolute neutrophil count (ANC) >= 1500/uL
• Hemoglobin >= 9 g/dL (5.58 mmol/L)
• Platelets >= 100,000/uL * If full-dose anticoagulation therapy is used, platelets >= 150,000/uL are required * If subject 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
• Serum creatinine =< 1.5 times the upper limit of normal (ULN) or Cockcroft-Gault calculated creatinine clearance >= 60 ml/min
• Total bilirubin =< 1.5 mg/dL (25.65 umol/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
• Subjects 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 subjects 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
• Subjects 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 subject 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. Subjects 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
• Patient with a history of or concurrent second primary malignancy (stage III or IV) within 5 years to study enrollment are excluded
• Patients with a history of prior invasive malignancy (except early-stage I or II nonmelanomatous 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
• Subjects 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