A Phase II Trial Of Ipilimumab In Combination With Nivolumab In Patients With Advanced Nasopharyngeal Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Ipilimumab
- Conditions
- Nasopharyngeal Carcinoma
- Sponsor
- National Cancer Centre, Singapore
- Enrollment
- 113
- Locations
- 1
- Primary Endpoint
- Best Overall Response Rate (BOR) by RECIST
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this study is to test the hypothesis that a combined Immuno-Oncology (IO) strategy would see efficacy in a virally driven cancer like Nasopharyngeal Carcinoma (NPC). Hence, this is a combination study of nivolumab and ipilimumab in Epstein-Barr virus (EBV) driven nasopharyngeal carcinoma.
Detailed Description
Nasopharyngeal carcinoma (NPC) is endemic in Southern China and South-east Asia. Due to the peculiar chemosensitive nature of this disease and the low investment in drug development in Asia, there has been a paucity of new therapies for this disease. While response rates to repeated lines of chemotherapy average around 30%, the duration of disease control remains dismal and hence there is an unmet need to develop new therapies for this disease. These response rates are fairly similar to current monotherapy use of anti-PD1 agents in this group. Of specific interest, combined IO strategies have appear to add significantly to response rates in selected tumors such as melanoma, small cell lung cancer, and now Epidermal Growth Factor Receptor (EGFR) mutant lung cancers. It is hypothesized that a combined IO strategy would have similar if not better responses in a virally driven cancer like NPC. Hence this is a single arm study exploring the activity of a combination of nivolumab and ipilimumab in EBV driven nasopharyngeal carcinoma (NPC). The primary endpoint is best overall response rate. Secondary endpoints will examine clinical benefit rate at 18 weeks, toxicities of the combination, and immunological correlates.
Investigators
Eligibility 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.
- •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
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
Arms & Interventions
Nivolumab and Ipilimumab
Intervention: Ipilimumab
Nivolumab and Ipilimumab
Intervention: Nivolumab
Outcomes
Primary Outcomes
Best Overall Response Rate (BOR) by RECIST
Time Frame: From the start of treatment until disease progression/recurrence, up to 2 years
The proportion of patients who experienced a BOR of Complete Response (CR) or Partial Response (PR).
Secondary Outcomes
- Progression-free survival(Time from first dose with IO agents until objective tumour progression, or death from any cause, whichever occurs first, up to 2 years)