CD8+ T Cell Imaging During Pre-surgery Immunotherapy in People With Melanoma

Study Overview
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Brief Summary
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Combination treatment with nivolumab and ipilimumab before surgery may help people with melanoma because the drugs are designed to help the immune system target and destroy cancer cells (immunotherapy), which may shrink the cancer and prevent recurrence after surgery. Treatment given before surgery is called neoadjuvant therapy. The purpose of this study is to find out whether neoadjuvant therapy with nivolumab and ipilimumab can kill melanoma tumors before surgery and prevent disease from coming back after surgery. This study also explores a new, experimental PET scan that images the immune system to see if it is related to treatment outcomes.

Official Title
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CD8+ Cell Imaging During Neoadjuvant ImmunoTherapy (The C-IT Neo Trial)

Conditions
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Melanoma, Melanoma Stage III

Intervention / Treatment
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* Diagnostic Test: PET Scan
* Drug: Nivolumab
* Drug: Ipilimumab
* Procedure: Surgical Resection of Melanoma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is capable of understanding and complying with the protocol requirements and has signed the Informed Consent document. Adults at least 18 years of age Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 Cytologically or histologically confirmed stage IIIB, IIIC, IIID, or IV melanoma that can be surgically removed. Notes: In-transit melanoma is acceptable. Patients can enroll regardless of their BRAF mutational status 1cm of tumor needs to be visible on standard imaging (i.e. FDG PET or CT scan) Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L Neutrophils ≥ 1.5x109/L Platelets ≥ 100 x109/L Hemoglobin ≥ 5.5 mmol/L Creatinine ≤ 1.5x ULN AST ≤ 1.5 x ULN and ALT ≤ 1.5 x ULN Bilirubin ≤1.5 X ULN Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of study treatment (ipilimumab/nivolumab) Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of ipilimumab + nivolumab Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of study treatment (ipilimumab/nivolumab) Note: Women who are not of childbearing potential (i.e., who are postmenopausal), or surgically sterile as well as azoospermic men do not require contraception Exclusion Criteria: Subjects with any active autoimmune disease (current symptoms or requirement for immunosuppression at the time of study start). Positive active hepatitis B viral infection (+viral load by PCR) Prior immunotherapy targeting CTLA-4 and/or PD-1/PD-L1 for any disease. Potentially unresectable melanoma. History of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) History of severe hypersensitivity reaction to any monoclonal antibody Underlying medical conditions that, in the Investigator's opinion, will make the administration of treatment hazardous or obscure the interpretation of toxicity Patients who have undergone splenectomy or have other splenic disorders. The normal spleen usually has CD8+ cell activity and serves as a positive control to enable proper imaging technique. Use of other investigational drugs before study drug administration 30 days and 5 half-times before study inclusion Pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with Stage III Melanoma<br>All participants will have cytologically or histologically confirmed stage IIIB, IIIC, IIID melanoma that can be surgically removed. | Diagnostic Test: PET Scan<br>* Patients will have a baseline CD8 PET scan prior to one dose of neoadjuvant nivolumab 1mg/kg + ipilimumab 3mg/kg. After 4 weeks, patients will have a repeat CD8 PET scan and then undergo surgical resection of their stage III melanoma.<br>* Other names: 89Zr-Df-Crefmirlimab;Drug: Nivolumab<br>* Patients will have a baseline CD8 PET scan prior to receiving one dose of neoadjuvant nivolumab 1mg/kg + ipilimumab 3mg/kg.<br>Drug: Ipilimumab<br>* Patients will have a baseline CD8 PET scan prior to receiving one dose of neoadjuvant nivolumab 1mg/kg + ipilimumab 3mg/kg.<br>Procedure: Surgical Resection of Melanoma<br>* Patients will have a baseline CD8 PET scan prior to one dose of neoadjuvant nivolumab 1mg/kg + ipilimumab 3mg/kg. After 4 weeks, patients will have a repeat CD8 PET scan and then undergo surgical resection of their stage III melanoma.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathologic responses/MPR | Participants' disease will be assessed for MPR as per previously established criteria for neoadjuvant trials (near complete response ≤10% viable; complete response 0% viable). Pathologic response (≤50% viable) will also be estimated. | up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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21-456, CD8+ Cell Imaging, C-IT Neo Trial, stage III melanoma, 89Zr-Df-Crefmirlimab, Memorial Sloan Kettering Cancer Center