Radioiodine (RAI) in Combination With Durvalumab (Medi4736) for RAI-avid, Recurrent/Metastatic Thyroid Cancers
Overview
- Phase
- Early Phase 1
- Intervention
- Durvalumab (Medi4736)
- Conditions
- Thyroid Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 11
- Locations
- 7
- Primary Endpoint
- Number of Patients With Dose-Limiting Toxicity (DLTs)
- Status
- Active, not recruiting
- Last Updated
- 9 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •(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)
Exclusion Criteria
- •131I 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
- •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).
Arms & Interventions
Radioiodine (RAI) in Combination with Durvalumab (Medi4736)
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.
Intervention: Durvalumab (Medi4736)
Radioiodine (RAI) in Combination with Durvalumab (Medi4736)
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.
Intervention: Radioiodine (RAI)
Outcomes
Primary Outcomes
Number of Patients With Dose-Limiting Toxicity (DLTs)
Time Frame: 6 weeks beginning from the first durvalumab
Grading of DLTs will follow the guidelines provided in the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Secondary Outcomes
- Best Overall Response(2 years)