Clinical Trials /

Phase 2 Trial of Ipilimumab and Nivolumab in Nasopharyngeal Carcinoma

NCT03097939

Description:

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.

Related Conditions:
  • Nasopharyngeal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Trial of Ipilimumab and Nivolumab in Nasopharyngeal Carcinoma
  • Official Title: A Phase II Trial Of Ipilimumab In Combination With Nivolumab In Patients With Advanced Nasopharyngeal Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: CA209-796
  • NCT ID: NCT03097939

Conditions

  • Nasopharyngeal Carcinoma

Interventions

DrugSynonymsArms
IpilimumabYervoyNivolumab and Ipilimumab
NivolumabOpdivo, BMS-936558Nivolumab and Ipilimumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab and IpilimumabExperimental
  • Ipilimumab
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed Epstein-Barr Encoded RNA
             (EBER) positive NPC

          -  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. Pts who progress
             within 1 year of chemoradiation for locally advanced disease are allowed on study.

          -  Age > 21

          -  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 antibody

          -  Prisoners or subjects who are involuntarily incarcerated

          -  Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (eg, infectious disease) illness

          -  Inability to comply with restrictions and prohibited activities/treatments in this
             study

          -  Subjects with concomitant second malignancies (except adequately treated
             non-melanomatous skin cancers, in situ cervical cancers, localized prostate cancer or
             in situ breast cancer) are excluded unless a complete remission was achieved at least
             3 years prior to study entry and no additional therapy is required or anticipated to
             be required
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:21 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Best Overall Response Rate (BOR) by RECIST
Time Frame:From the start of treatment until disease progression/recurrence, up to 2 years
Safety Issue:
Description:The proportion of patients who experienced a BOR of Complete Response (CR) or Partial Response (PR).

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Centre, Singapore

Last Updated

April 22, 2018