RAI Plus Immunotherapy for Recurrent/Metastatic Thyroid Cancers

NCT03215095 | Active Not Recruiting Early Phase 1 Results FDA Drug

• 1 other identifier: 17-218
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to find out what effects, good and/or bad, a drug called durvalumab combined with Thyrogen-stimulated RAI, has on the patient and thyroid cancer. Durvalumab is a drug that has been developed to activate the immune system by blocking a protein called programmed death ligand-1 (PD-L1) that can be present on tumor and normal cells, including immune cells.

Conditions

Thyroid Cancer

Keywords

Radioiodine (RAI); Durvalumab (Medi4736); RAI-avid; 17-218

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Dose-Limiting Toxicity (DLTs)

  Grading of DLTs will follow the guidelines provided in the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  6 weeks beginning from the first durvalumab

Secondary Outcomes (1)

• Best Overall Response

  2 years

Study Arms (1)

Radioiodine (RAI) in Combination with Durvalumab (Medi4736)

EXPERIMENTAL

Enrolled patients will be treated with durvalumab 1500 mg IV every 4 weeks. In Cycle 1/Week 3, Thyrogen 0.9 mg IM will be administered on two consecutive calendar days followed by 100 mCi (+/- 10 mCi) of RAI the next calendar day. Durvalumab will be continued every 4 weeks.

Drug: Durvalumab (Medi4736); Radiation: Radioiodine (RAI)

Interventions

Durvalumab (Medi4736) DRUG

durvalumab 1500 mg IV every 4 weeks

Radioiodine (RAI) in Combination with Durvalumab (Medi4736)

Radioiodine (RAI) RADIATION

100 mCi (+/- 10 mCi) of 131I will be administered a day after Thyrogen injections have been administered for two consecutive calendar days.

Radioiodine (RAI) in Combination with Durvalumab (Medi4736)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed thyroid carcinoma of follicular origin (including papillary, follicular, hurthle cell or poorly differentiated subtypes and their respective variants).
• Diagnosis of recurrent and/or metastatic thyroid cancer
• At least one RAI-avid lesion identified on the most recent radioiodine scan (a diagnostic, post-therapy, or post-ablation scan) OR at least one lesion on the most recent FDG PET scan with an SUV max of 10 or less. (Both RAI-sensitive and RAI-refractory patients are eligible if at least one tumor with RAI avidity of any degree can be identified within one of these parameters.)
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease. Tumors in previously irradiated fields may be considered measureable if there is evidence of tumor progression after radiation treatment.
• ECOG Performance Status (PS) 0 or 1. (or Karnofsky ≥60%)
• Age ≥ 18 years at time of study entry
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (\> 1500 per mm\^3)
• Platelet count ≥ 100 x 10\^9/L (\>100,000 per mm\^3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). (This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.)
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
• Serum creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Males:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) . 72 x serum creatinine (mg/dL)

You may not qualify if:

• I therapy \< 6 months prior to initiation of therapy on this protocol. A diagnostic study using \< 10 mCi of 131I is not considered 131I therapy.
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
• History of pneumonitis.
• External beam radiation therapy \< 4 weeks prior to initiation of therapy on this protocol.
• Chemotherapy, immunotherapy, targeted therapy, monoclonal antibodies, tumor embolization, or other investigational agent within 28 days prior to the first dose of study drug.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
• Any unresolved toxicity CTCAE grade ≥ 2 from previous anti-cancer therapy. Exceptions include hearing loss, peripheral neuropathy, and alopecia.
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1.
• Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with a history of autoimmune thyroid disease are not excluded. Subjects with vitiligo or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of primary immunodeficiency.
• History of allogeneic organ transplant.
• History of hypersensitivity to durvalumab or any excipient.
• History of hypersensitivity to thyrotropin alpha (Thyrogen).
• Patients unable to follow a low iodine diet or requiring medication with high content in iodide (amiodarone).

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• AstraZeneca: collaborator
• MedImmune LLC: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

durvalumab; Iodine-131

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Results Point of Contact

• Title: Dr. Alan Ho, MD, PhD
• Organization: Memorial Sloan Kettering Cancer Center

hoa@mskcc.org

646-608-3774

Study Officials

• Alan Ho, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a pilot study with the primary objective to assess the safety of administering the PD-L1 targeting agent durvalumab in combination with recombinant human thyroid stimulating hormone (rhTSH, Thyrogen) stimulated/prepared radioiodine (RAI; 131I) therapy in patients with RAI-avid (RAIA) recurrent and/or metastatic (R/M) thyroid cancer.

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: July 12, 2017
• Study Start: July 10, 2017
• Primary Completion: February 6, 2023
• Study Completion (Estimated): July 1, 2026
• Last Updated: July 17, 2025
• Results First Posted: March 22, 2024

Record last verified: 2025-07

Locations

US (7)