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.
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.
