Phase 2 Trial of Ipilimumab and Nivolumab in Nasopharyngeal Carcinoma

NCT03097939 | Unknown Phase 2

• 1 other identifier: CA209-796
• Study Type: interventional
• Target: 113
• Locations: 1 country
• Sites: 1

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.

Conditions

Nasopharyngeal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate (BOR) by RECIST

  The proportion of patients who experienced a BOR of Complete Response (CR) or Partial Response (PR).

  From the start of treatment until disease progression/recurrence, up to 2 years

Secondary Outcomes (1)

• 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

Study Arms (1)

Nivolumab and Ipilimumab

EXPERIMENTAL

Drug: Ipilimumab; Drug: Nivolumab

Interventions

Ipilimumab DRUG

1 mg/kg of IV Ipilimumab is admistered over 90 minutes every 6 weeks

Also known as: Yervoy

Nivolumab and Ipilimumab

Nivolumab DRUG

3 mg/kg of IV Nivolumab is administered over 30 minutes every 2 weeks

Also known as: Opdivo, BMS-936558

Nivolumab and Ipilimumab

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• National University of Singapore: collaborator
• National Taiwan University Hospital: collaborator

Study Sites (1)

National Cancer Center Singapore

Singapore, 169610, Singapore

RECRUITING

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Darren, Wan-Teck Lim, MD

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Darren, Wan-Teck Lim, MD

CONTACT

+65 6436 8000; darren.lim.w.t@singhealth.com.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2017
• First Posted: March 31, 2017
• Study Start: March 31, 2017
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: October 11, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)