Clinical Trials /

CLR 131 Combined With Radiation for Head and Neck Cancer

NCT04105543

Description:

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.

Related Conditions:
  • Malignant Head and Neck Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CLR 131 Combined With Radiation for Head and Neck Cancer
  • Official Title: Therapeutic Combination of CLR 131 With External Beam Radiation in Head and Neck Cancer

Clinical Trial IDs

  • ORG STUDY ID: UW19041
  • SECONDARY ID: P50DE026787
  • SECONDARY ID: 2019-0681
  • SECONDARY ID: 17-030-E
  • SECONDARY ID: A534260
  • SECONDARY ID: SMPH/MEDICINE/HEM-ONC
  • SECONDARY ID: NCI-2019-05419
  • SECONDARY ID: Protocol Version 7/7/2020
  • NCT ID: NCT04105543

Conditions

  • Head and Neck Cancer

Interventions

DrugSynonymsArms
CLR 131I-131-CLR1404CLR 131 Dose Escalation

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
CLR 131 Dose EscalationExperimentalEnrollment 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

Eligibility Criteria

        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.

          -  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 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
             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

          -  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
             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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Adverse Events
Time Frame:up to 18 weeks
Safety Issue:
Description:Incidence of adverse events assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Secondary Outcome Measures

Measure:CLR 131 Tumor Uptake via SPECT/CT Imaging
Time Frame:Up to 8 days
Safety Issue:
Description:Investigators will use SPECT/CT imaging scans to predict the adsorbed dose of CLR 131 to tumors with the Monte Carlo method.
Measure:Median Radiation Treatment Time
Time Frame:up to 14 weeks
Safety Issue:
Description:
Measure:Median Number of Dose Delays Due to Toxicity
Time Frame:up to 14 weeks
Safety Issue:
Description:
Measure:Overall Response Rate (ORR)
Time Frame:up to 9 months
Safety Issue:
Description: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).
Measure:Change in Swallow Function: DIGEST Scale
Time Frame:up to 9 months
Safety Issue:
Description: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.
Measure:Change in Quality of Life: MDADI Score
Time Frame:up to 15 months
Safety Issue:
Description: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.
Measure:Change in Stimulated Salivary Flow
Time Frame:up to 9 months
Safety Issue:
Description:Change in Stimulated Salivary Flow before and after treatment (mL/min).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Wisconsin, Madison

Last Updated

July 27, 2020