Nivolumab and Ipilimumab in People With Aggressive Pituitary Tumors

Study Overview
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Brief Summary
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The purpose of this study is to determine if nivolumab and ipilimumab are effective treatment for people with pituitary tumors have gotten worse after surgery and radiation.

Official Title
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Phase II Trial of Nivolumab Plus Ipilimumab in Patients With Aggressive Pituitary Tumors

Conditions
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Pituitary, Pituitary Tumor, Pituitary Carcinoma, Pituitary Cancer

Intervention / Treatment
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* Drug: Ipilimumab
* Drug: Nivolumab
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 18 A pituitary adenoma/carcinoma of any histology ° Patients with unresectable tumors that are radiographically (and/or biochemically) consistent with a pituitary adenoma may be considered for enrollment without pathologic confirmation with approval from the principal investigator. Progression on imaging following radiotherapy ° Patients with pituitary carcinomas in whom there is not felt to be a palliative benefit to treatment with radiotherapy are eligible for enrollment without prior radiotherapy. Measurable disease by RANO criteria At least 4 weeks have elapsed since the patient last received temozolomide and the patient must have recovered hematologically from other chemotherapeutics Karnofsky Performance Status (KPS) greater than or equal to 70 Screening laboratory values must meet the following criteria: WBC >/= 2000/uL Neutrophils >/= 1500/uL Platelets >/= 100 x 10^3/uL Hemoglobin > 9.0 g/dL AST/ALT </=3 x ULN Total Bilirubin </= 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin <3.0 mg/dL) Serum creatinine </= 1.5 x ULN or creatinine clearance (CrCl) >/= 40 mL/min using the Cockcroft-Gault formula Women of childbearing potential (WOCBP) must use appropriate method(s) or 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 investigational drug WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. Women who are not of childbearing potential are not required to use contraception Women of childbearing potential must have a negative serum or urine pregnancy test upon study entry Men who are sexually active with women of childbearing potential must use adequate contraception upon study entry until 31 weeks after the last dose of study treatment. Men who are surgically sterile or azoospermic do not require contraception. Exclusion Criteria: A corticosteroid requirement of greater than 4mg per day of dexamethasone (or an equivalent dose). NOTE: Patients requiring a physiologic replacement dose of corticosteroids, who may require stress dose corticosteroids, due to adrenal insufficiency are permitted onto this trial Active, known, or suspected autoimmune disease within the past 2 years. NOTE: Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger Patients should be excluded if they have had prior systemic treatment with a CTLA-4 antibody. Prior treatment with PD1 or PD-L1 antibodies are permitted as long as the patient did not experience serious toxicities requiring treatment discontinuation related to prior PD-1 or PD-L1 therapy Patients should be excluded if they have a known history of testing positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus antibody (HCV antibody) indicating acute or chronic infection Patients should be excluded if they have a known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) History of allergy to study drug components History of severe hypersensitivity reaction to any monoclonal antibody Women who are pregnant or breast-feeding Inability to undergo radiographic surveillance

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: Pituitary Cancer<br>Participants will have a pituitary adenoma/carcinoma of any histology | Drug: Ipilimumab<br>* Ipilimumab 3 mg/kg every 3 weeks,<br>Drug: Nivolumab<br>* Nivolumab 1 mg/kg every 3 weeks for 4 cycles<br>Drug: Nivolumab<br>* Following concurrent ipilimumab and nivolumab, patients will receive single agent nivolumab at 480 mg every 4 weeks for 6 cycles (1 cycle=4 weeks) with the option of continuing until disease progression or until the end of the study, whichever occurs first<br>* Other names: Single agent Nivolumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic response rate | Radiographic response rate will be assessed by RANO/iRANO | 36 weeks from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as assessed by CTCAE 5.0 | Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0 will be used to assess safety | 36 weeks from baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pituitary tumor, Nivolumab, Ipilimumab, 19-216