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 24 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.
- 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
- 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.
- 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
- 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
- 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.
- 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
- 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
- Participants with a history of or concurrent second primary malignancy (stage III or
IV) within 5 years to study enrollment are excluded.
- Participants with with a history of or concurrent second primary malignancy (stage I
or II) that have been 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
- 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
- Serious or non-healing wound, ulcer, or bone fracture
- 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
- 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.