Phase 2 Trial of Ipilimumab and Nivolumab in Nasopharyngeal Carcinoma

• Register: ClinicalTrials.gov
• Last refreshed on: 23 October 2023
• Main ID: NCT03097939
• Date of registration: 22/03/2017
• Prospective Registration: Yes
• Primary sponsor: National Cancer Centre, Singapore
• Public title: Phase 2 Trial of Ipilimumab and Nivolumab in Nasopharyngeal Carcinoma
• Scientific title: A Phase II Trial Of Ipilimumab In Combination With Nivolumab In Patients With Advanced Nasopharyngeal Carcinoma
• Date of first enrolment: March 31, 2017
• Target sample size: 113
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03097939
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Singapore

Contacts

• Name: Darren, Wan-Teck Lim, MD

• Name: Darren, Wan-Teck Lim, MD
• Affiliation: National Cancer Centre, Singapore

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients with recurrent and/or metastatic nasopharyngeal carcinoma, which is not
feasible for curative therapy.

- Patients must have histologically or cytologically confirmed NPC with Epstein-Barr
Encoded RNA (EBER) positive tumour cells and/or elevated serum EBV DNA viral titres.

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded for
non-nodal lesions and short axis for nodal lesions) as >20 mm with conventional
techniques or as >10 mm with spiral CT scan, MRI, or calipers by clinical exam.

- No more than 1 line of previous chemotherapy and/or targeted therapy or patients who
do not tolerate chemotherapy. Pts who progress within 1 year of chemoradiation for
locally advanced disease are allowed on study.

- Age > 21. In Taiwan, patients with who are older than 20 years old are eligible

- Life expectancy > 3 months

- Eastern Cooperative Oncology Group (ECOG) 0-1

- Patients must have normal organ and marrow function as defined below:

- White Blood Cells (WBC) = 2000/µL

- Neutrophils = 1500/µL

- Platelets = 100 x103/µL

- Hemoglobin > 9.0 g/dL

- Serum creatinine = 1.5 x Upper Limit of Normal (ULN) or creatinine clearance
(CrCl) = 40 mL/min (if using the Cockcroft-Gault formula below):

- Female CrCl = [(140 - age in years) x weight in kg x 0.85] ÷ (72 x serum
creatinine in mg/dL)

- Male CrCl = [(140 - age in years) x weight in kg x 1.00] ÷ (72 x serum
creatinine in mg/dL)

- Aspartate Transaminase/Alanine Transaminase (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)

- Measurable levels of circulating EBV DNA

- 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/ipilimumab to undergo five half-lives) after
the last dose of investigational drug

- 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 nivolumab/ipilimumab

- Women must not be breastfeeding

- 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/ipilimumab 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 investigational product. Women who are not of
childbearing potential (ie, who are postmenopausal or surgically sterile as well as
azoospermic men do not require contraception

- Ability to understand and the willingness to sign a written informed consent document.

- Any surgery must be more than 28 days before start of study drug and any surgical
wounds must be completely healed

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.

- Patients who are receiving any other investigational agents.

- Patients are excluded if they have active brain metastases or leptomeningeal
metastases. Subjects with brain metastases are eligible if metastases have been
treated and there is no magnetic resonance imaging (MRI) evidence of progression for
[lowest minimum is 4 weeks or more] after treatment is complete and within 28 days
prior to the first dose of IO administration. There must also be no requirement for
immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone
equivalents) for at least 2 weeks prior to study drug administration.

- Patients should be excluded if they are positive test for hepatitis B virus surface
antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating
acute or chronic infection.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to nivolumab or ipilimumab.

- Prior use of anti-PD1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or
any drug specifically targeted T-cell costimulatory checkpoint pathways

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant women are excluded from this study because ipilimumab has the potential for
teratogenic or abortifacient effects. Because there is an unknown but potential risk
for adverse events in nursing infants secondary to treatment of the mother with
nivolumab or ipilimumab, breastfeeding should be discontinued if the mother is treated
with nivolumab or ipilimumab.

- Patients should be excluded if they have known history of testing positive for human
immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)

- Patients should be excluded if they have an active, known or suspected autoimmune
disease. 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 a condition requiring systemic treatment with
either corticosteroids (> 10 mg daily prednisone equivalents) or other
immunosuppressive medications within 14 days of study drug administration. Inhaled or
topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents
are permitted in the absence of active autoimmune disease.

- Patient should be excluded if they have history or active interstitial lung disease
(pneumonitis).

- Prior organ allograft or allogeneic bone marrow transplantation

- Allergies and Adverse Drug Reaction

- History of allergy to study drug components

- History of severe hypersensitivity reaction to any monoclonal an


Age minimum: 21 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Nasopharyngeal Carcinoma

Intervention(s)

Drug: Nivolumab

Drug: Ipilimumab

Primary Outcome(s)

Best Overall Response Rate (BOR) by RECIST [Time Frame: From the start of treatment until disease progression/recurrence, up to 2 years]

Secondary Outcome(s)

Progression-free survival [Time Frame: Time from first dose with IO agents until objective tumour progression, or death from any cause, whichever occurs first, up to 2 years]

Secondary ID(s)

CA209-796

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National University of Singapore

National Taiwan University Hospital