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Combination Radiotherapy and Radiopharmaceutical Therapy Treatment Planning for Thyroid Cancer

Primary Purpose

Recurrent Thyroid Cancer

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Combination treatment (CXRPT) of external beam radiation (XRT) plus radioactive iodine (RAI)

About this trial

This is an interventional treatment trial for Recurrent Thyroid Cancer

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion:

18 and 85 years, inclusive.
Histologically confirmed papillary or follicular thyroid carcinoma, collectively referred to as differentiated thyroid carcinoma (DTC), that is incompletely responsive to initial surgery +/- 131-Iodine as established by anatomic imaging (CT, MRI, and Ultrasound).
DTC that is not completely resectable with macroscopic invasion of tumor into cervical soft tissues and/or non-resectable distant metastases.
Iodine avid residual disease, but with a sub-therapeutic level of lesional radioiodine uptake demonstrated in either a pre-treatment diagnostic scan or a previous post-treatment radioiodine scan, making it unlikely that the patient would benefit from radioiodine therapy alone.
Adequate organ function, including: a) adequate renal function, defined as a measured creatinine clearance >70 ml/min/1.73 m2 or normal radioisotope glomerular filtration rate (GFR); and b) adequate hematologic function, defined as a platelet count > 50,000 cells/mm3 and an absolute neutrophil count (ANC) > 500 cells/mm3
Life expectancy of at least 8 weeks.
Karnofsky performance status (KPS) > 50%
Patients must have adequately recovered from the effects of any prior chemotherapy, as determined by the treating physician and study team, based in part on organ function defined above. Toxicities from previous therapies must have recovered to CTCAE v5.0 grade 2 or better.
Patients with previously identified cardiac disease will be eligible, as Sodium Iodide I-131 (131I NaI) is not expected to cause cardiac dysfunction

Exclusion:

Patient is pregnant or breastfeeding.
Patient is sexually active, premenopausal, and does not agree to use accepted, effective forms of contraception.
Any criteria that would contraindicate radioiodine therapy or external beam radiotherapy.
Patient having alimentary toxic aleukia (ATA) low and intermediate risk tumors, not meeting the guidelines for either radioactive iodine (RAI) treatment or External beam radiotherapy (EBRT).
Patient with advanced central nervous system (CNS) metastatic disease, critical lesions in the hip and spine, etc. that would make RAI treatment prior to EBRT potentially harmful, with respect to worsening of disease as a result of the recombinant thyroid-stimulating hormone (TSH) stimulation.
Patients having recent exposure to iodinated contrast (within 6 weeks, that could render RAI treatment ineffective).

Sites / Locations

The Johns Hopkins SKCCCRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

High-risk thyroid cancer patients

Arm Description

All study patients will have histologically confirmed recurrence of thyroid cancer that is incompletely responsive to initial surgery.

Outcomes

Primary Outcome Measures

Safety of combined therapy of XRT plus RAI measured by NCI-CTCAE toxicity

Toxicity of combined XRT plus RAI defined by the incidence of grade 3 or greater toxicities as measured with National Cancer Institutes-Common Terminology Criteria for Adverse Events (CTCAE)

Safety of combined therapy of XRT plus RAI measured by NCI-CTCAE toxicity

Toxicity of combined XRT plus RAI defined by the incidence of grade 3 or greater toxicities as measured with National Cancer Institutes-Common Terminology Criteria for Adverse Events (CTCAE)

Secondary Outcome Measures

Tumor Response (1)

Measure tumor response upon SPECT imaging

Tumor Response (2)

Measure tumor response by Response evaluation criteria in solid tumors (RECIST) criteria

Tumor Response (3)

Measure tumor response by change in unstimulated serum thyroglobulin (with Thyroglobulin Antibody).

Full Information

NCT ID

NCT04892303

First Posted

May 3, 2021

Last Updated

May 30, 2023

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT04892303

Brief Title

Combination Radiotherapy and Radiopharmaceutical Therapy Treatment Planning for Thyroid Cancer

Official Title

Combination Radiotherapy and Radiopharmaceutical Therapy Treatment Planning for Thyroid Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 17, 2021 (Actual)

Primary Completion Date

December 2027 (Anticipated)

Study Completion Date

December 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The goal of this study is to evaluate combined radioactive iodine (RAI, 131-I) and external beam radiotherapy (XRT) to optimize the radiation dose delivered to treat well differentiated thyroid cancers (DTC) with iodine-avid metastases. The investigators hypothesize that precise dosimetric planning will permit this combined RAI-XRT radiotherapeutic approach to be safe and permit higher tumor radiation doses than could otherwise be delivered. Patients with metastatic well-differentiated DTC) that is not completely resectable with macroscopic invasion of tumor into cervical soft tissues and/or non-resectable distant metastases, are the target study population. The primary objective is to evaluate safety as defined by the incidence of maximum grade 3 or greater NCI CTCAE toxicity observed during the treatment period and for the first 30 days following completion of radiotherapy. Secondary endpoints will evaluate efficacy at 6 months and feasibility of this combination to deliver a minimum cumulative dose of 80 Gy to the index tumors selected prior to treatment initiation. The investigators plan to enroll 48 subjects at an accrual rate of 1 subject per month over a study duration of 4 years.

Detailed Description

The study goal is to evaluate combined radioactive iodine (RAI, 131-I) and external beam radiotherapy (XRT) to optimize the radiation dose delivered to treat well-differentiated thyroid cancers (DTC) with iodine-avid metastases, hypothesizing that this combination approach is safe and enables delivery of higher local radiation doses than could otherwise be safely delivered with either radiotherapeutic modality alone. This is an open-labeled, phase 1 clinical trial design that will enroll study subjects with recurrent DTC that is not completely resectable with macroscopic invasion of tumor into cervical soft tissues and/or non-resectable distant metastases. Study subjects will have a sub-therapeutic level of lesional RAI uptake demonstrated in either a pre-treatment diagnostic scan or a previous post-treatment radioiodine scan, making it unlikely that the patient would fully benefit from RAI therapy alone. The primary objective is evaluate safety as defined by the incidence of maximum grade 3 or greater NCI CTCAE grade toxicity observed during the treatment period and for the first 30 days following completion of radiotherapy. Additional secondary endpoints will evaluate efficacy at 6 months and feasibility of this combination to deliver a minimum cumulative dose of 80 Gy (66 Gy, Equivalent dose in 2Gy fractions (EQD2); 2 Gy per fraction) to the index tumors (up to 3 in each study subject) selected prior to treatment initiation. The investigators plan to enroll 48 subjects at an accrual rate of 1 subject per month over a study duration of 4 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Recurrent Thyroid Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Model Description

This is a Phase 1, prospective, open-label treatment study.

Masking

None (Open Label)

Masking Description

No masking

Allocation

N/A

Enrollment

48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

High-risk thyroid cancer patients

Arm Type

Other

Arm Description

All study patients will have histologically confirmed recurrence of thyroid cancer that is incompletely responsive to initial surgery.

Intervention Type

Combination Product

Intervention Name(s)

Combination treatment (CXRPT) of external beam radiation (XRT) plus radioactive iodine (RAI)

Other Intervention Name(s)

radiopharmaceutical (RPT)

Intervention Description

To safely administer a minimum cumulative dose of external beam radiation to up 3 index tumors per patient, supplemented radiation dose delivered by radioactive iodine (RAI)

Primary Outcome Measure Information:

Title

Safety of combined therapy of XRT plus RAI measured by NCI-CTCAE toxicity

Description

Toxicity of combined XRT plus RAI defined by the incidence of grade 3 or greater toxicities as measured with National Cancer Institutes-Common Terminology Criteria for Adverse Events (CTCAE)

Time Frame

During external beam radiation therapy (over a 2 week period)

Title

Safety of combined therapy of XRT plus RAI measured by NCI-CTCAE toxicity

Description

Toxicity of combined XRT plus RAI defined by the incidence of grade 3 or greater toxicities as measured with National Cancer Institutes-Common Terminology Criteria for Adverse Events (CTCAE)

Time Frame

Within 30 days of completing external beam radiation therapy

Secondary Outcome Measure Information:

Title

Tumor Response (1)

Description

Measure tumor response upon SPECT imaging

Time Frame

6 months

Title

Tumor Response (2)

Description

Measure tumor response by Response evaluation criteria in solid tumors (RECIST) criteria

Time Frame

6 months

Title

Tumor Response (3)

Description

Measure tumor response by change in unstimulated serum thyroglobulin (with Thyroglobulin Antibody).

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion: 18 and 85 years, inclusive. Histologically confirmed papillary or follicular thyroid carcinoma, collectively referred to as differentiated thyroid carcinoma (DTC), that is incompletely responsive to initial surgery +/- 131-Iodine as established by anatomic imaging (CT, MRI, and Ultrasound). DTC that is not completely resectable with macroscopic invasion of tumor into cervical soft tissues and/or non-resectable distant metastases. Iodine avid residual disease, but with a sub-therapeutic level of lesional radioiodine uptake demonstrated in either a pre-treatment diagnostic scan or a previous post-treatment radioiodine scan, making it unlikely that the patient would benefit from radioiodine therapy alone. Adequate organ function, including: a) adequate renal function, defined as a measured creatinine clearance >70 ml/min/1.73 m2 or normal radioisotope glomerular filtration rate (GFR); and b) adequate hematologic function, defined as a platelet count > 50,000 cells/mm3 and an absolute neutrophil count (ANC) > 500 cells/mm3 Life expectancy of at least 8 weeks. Karnofsky performance status (KPS) > 50% Patients must have adequately recovered from the effects of any prior chemotherapy, as determined by the treating physician and study team, based in part on organ function defined above. Toxicities from previous therapies must have recovered to CTCAE v5.0 grade 2 or better. Patients with previously identified cardiac disease will be eligible, as Sodium Iodide I-131 (131I NaI) is not expected to cause cardiac dysfunction Exclusion: Patient is pregnant or breastfeeding. Patient is sexually active, premenopausal, and does not agree to use accepted, effective forms of contraception. Any criteria that would contraindicate radioiodine therapy or external beam radiotherapy. Patient having alimentary toxic aleukia (ATA) low and intermediate risk tumors, not meeting the guidelines for either radioactive iodine (RAI) treatment or External beam radiotherapy (EBRT). Patient with advanced central nervous system (CNS) metastatic disease, critical lesions in the hip and spine, etc. that would make RAI treatment prior to EBRT potentially harmful, with respect to worsening of disease as a result of the recombinant thyroid-stimulating hormone (TSH) stimulation. Patients having recent exposure to iodinated contrast (within 6 weeks, that could render RAI treatment ineffective).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Dana B. Kaplin, MPH

Phone

410-614-3950

dkaplin1@jhmi.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Harry Quon, MD

Phone

410-502-3877

hquon2@jhmi.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Harry Quon, MD

Organizational Affiliation

Johns Hopkins, School of Medicine, Radiation Oncology

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Johns Hopkins SKCCC

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Harry Quon, M.D.

Phone

410-502-3877

hquon2@jhmi.edu

First Name & Middle Initial & Last Name & Degree

George Sgouros, PhD

First Name & Middle Initial & Last Name & Degree

Robert Hobbs, PhD

First Name & Middle Initial & Last Name & Degree

Paul Ladenson, MD

First Name & Middle Initial & Last Name & Degree

Prasanna Santhanam, MBBS

12. IPD Sharing Statement

Learn more about this trial

Combination Radiotherapy and Radiopharmaceutical Therapy Treatment Planning for Thyroid Cancer

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