Nivolumab and Ipilimumab in People With Aggressive Pituitary Tumors

Pituitary Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04042753
• Other study ID #: 19-216
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 31, 2019
• Est. completion date: July 2024

Study information

• Verified date: June 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 9
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pituitary
• Pituitary Cancer
• Pituitary Carcinoma
• Pituitary Diseases
• Pituitary Neoplasms
• Pituitary Tumor

Intervention

Drug:
• Ipilimumab
Ipilimumab 3 mg/kg every 3 weeks,
• Nivolumab
Nivolumab 1 mg/kg every 3 weeks for 4 cycles
• 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

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Cancer Center @ Commack (Limited Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiographic response rate	Radiographic response rate will be assessed by RANO/iRANO	36 weeks from baseline
Secondary	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

External Links

•   Memorial Sloan Kettering Cancer Center