Nivolumab and Ipilimumab in People With Aggressive Pituitary Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Pituitary; Pituitary Tumor; Pituitary Cancer; Pituitary Carcinoma
• Intervention / Treatment: Drug: Ipilimumab; Drug: Nivolumab; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center @ Commack (Limited Protocol Activities)
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center (All Protocol Activities)
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pituitary Cancer; Participants will have a pituitary adenoma/carcinoma of any histology

Drug: Ipilimumab; Ipilimumab 3 mg/kg every 3 weeks,; Drug: Nivolumab; Nivolumab 1 mg/kg every 3 weeks for 4 cycles; Drug: Nivolumab; 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; Other Names: Single agent Nivolumab

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Andrew Lin, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Dai C, Liang S, Sun B, Kang J. The Progress of Immunotherapy in Refractory Pituitary Adenomas and Pituitary Carcinomas. Front Endocrinol (Lausanne). 2020 Dec 11;11:608422. doi: 10.3389/fendo.2020.608422. eCollection 2020.

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2019
• Primary Completion (Actual): June 1, 2026
• Study Completion (Actual): June 1, 2026

Study Registration Dates

• First Submitted: July 31, 2019
• First Submitted That Met QC Criteria: July 31, 2019
• First Posted (Actual): August 2, 2019

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Nivolumab; Ipilimumab; Pituitary tumor; 19-216
• Additional Relevant MeSH Terms: Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Pituitary Neoplasms; Pituitary Diseases; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; Ipilimumab
• Other Study ID Numbers: 19-216

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No