A Pilot Study of Durvalumab (MEDI4736) With Tremelimumab in Combination With Image Guided Stereotactic Body Radiotherapy (SBRT) in the Treatment of Metastatic Anaplastic Thyroid Cancer
Overview
- Phase
- Phase 1
- Intervention
- durvalumab
- Conditions
- Metastatic Anaplastic Thyroid Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 13
- Locations
- 8
- Primary Endpoint
- overall survival
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to test the safety of durvalumab (MEDI4736) and tremelimumab in combination with radiation therapy and find out what effects, if any, this combination has on people, and whether it improves overall survival.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histopathologic confirmation of anaplastic thyroid cancer (or histopathologic report consistent with anaplastic thyroid cancer) at Memorial Sloan Kettering Cancer Center with clinical evidence of metastatic disease not curable by either surgery or radiation therapy
- •Age ≥ 18 years at time of study entry
- •ECOG Performance Status of 0-2
- •Adequate normal organ and marrow function as defined below:
- •Hemoglobin ≥ 9.0 g/dL
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (≥ 1500 per mm\^3)
- •Platelet count ≥ 100 x 109/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 hyperbilirubinaemia 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:
Exclusion Criteria
- •Any previous treatment with an anti-CTLA4, including tremelimumab or any previous treatment with a PD1 or PDL1 inhibitor
- •Receipt of the last dose of any line of anti-cancer therapy (chemotherapy, immunotherapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, and other investigational agent) 7 days prior to the first dose of study drug and within 6 weeks for nitrosourea or mitomycin C Prior radiation therapy to targets other than the site currently being treated is permitted.
- •Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from a single electrocardiogram or average from 3 electrocardiograms (ECGs) using Frederica's Correction
- •Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab (MEDI4736) or tremelimumab, 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 any corticosteroid for more than 4 consecutive days
- •Any unresolved toxicity (CTCAE grade \> 1) from previous anti-cancer systemic therapy unless approved by one of the principal investigators (Drs. Lee or Sherman) Rare exceptions that would not affect the study (e.g., radiaton induced dysphagia) allowed with the consent of either principal investigators (Drs. Lee or Sherman)
- •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 vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. Rare exceptions allowed with the consent of both principal investigators (Drs. Lee and Sherman)
- •Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
- •Confirmed pneumonitis or interstitial lung disease
- •History of primary immunodeficiency
Arms & Interventions
durvalumab (MEDI4736) & tremelimumab with SBRT
Patients will receive durvalumab (MEDI4736) and tremelimumab together every 4 weeks. SBRT delivered to one metastatic site per standard of care using a standard 9Gy x 3 fractions will be given within 2 weeks after the completion of the first cycle of durvalumab (MEDI4736) and tremelimumab. After 4 cycles of durvalumab (MEDI4736) and tremelimumab, patients will then continue with single agent durvalumab (MEDI4736) every 4 weeks until disease progression or unacceptable toxicity or a total of 12 months from date of initial treatment.
Intervention: durvalumab
durvalumab (MEDI4736) & tremelimumab with SBRT
Patients will receive durvalumab (MEDI4736) and tremelimumab together every 4 weeks. SBRT delivered to one metastatic site per standard of care using a standard 9Gy x 3 fractions will be given within 2 weeks after the completion of the first cycle of durvalumab (MEDI4736) and tremelimumab. After 4 cycles of durvalumab (MEDI4736) and tremelimumab, patients will then continue with single agent durvalumab (MEDI4736) every 4 weeks until disease progression or unacceptable toxicity or a total of 12 months from date of initial treatment.
Intervention: tremelimumab
durvalumab (MEDI4736) & tremelimumab with SBRT
Patients will receive durvalumab (MEDI4736) and tremelimumab together every 4 weeks. SBRT delivered to one metastatic site per standard of care using a standard 9Gy x 3 fractions will be given within 2 weeks after the completion of the first cycle of durvalumab (MEDI4736) and tremelimumab. After 4 cycles of durvalumab (MEDI4736) and tremelimumab, patients will then continue with single agent durvalumab (MEDI4736) every 4 weeks until disease progression or unacceptable toxicity or a total of 12 months from date of initial treatment.
Intervention: Stereotactic Body Radiotherapy (SBRT)
Outcomes
Primary Outcomes
overall survival
Time Frame: 1 year
RECIST 1.1