Avelumab for Recurrent/Metastatic Nasopharyngeal Cancer

Brief Title

Avelumab for Recurrent/Metastatic Nasopharyngeal Cancer

Official Title

An Open-label, Single-arm, Multi-institutional Phase II Trial of Avelumab for Recurrent, Metastatic Nasopharyngeal Carcinoma

Brief Summary

      The purpose of this study is to determine whether avelumab, an investigational antibody
      against programmed death-ligand (PD-L1), has an effect on recurrent nasopharyngeal cancer.
      Avelumab is designed to block the interaction between programmed cell death protein 1 (PD-1),
      a known immune checkpoint, and PD-L1. By blocking this interaction, the immune system may be
      stimulated, allowing it to more effectively recognize and attack the cancer.
    

Detailed Description

      This is a prospective, multi-center, open-label, single-arm phase II trial to evaluate the
      efficacy of Avelumab for patients with recurrent/metastatic, Epstein-Barr virus (EBV)-related
      nasopharyngeal carcinoma.

      Upon study entry, all patients will receive Avelumab 10 milligrams per kilogram (mg/kg)
      intravenously (IV) on days 1 and 15 of each 28-day cycle. Treatment will be given until
      disease progression, unacceptable toxicity, investigator decision or patient withdrawal. Dose
      interruptions may occur per pre-specified criteria for grade 3 or higher toxicity.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Overall Response Rate

Condition

Nasopharyngeal Cancer

Intervention

Avelumab

Study Arms / Comparison Groups

 Avelumab

Description:  Avelumab 10mg/kg IV infusion on days 1 and 15 of 28-day cycle

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

6

Start Date

January 2017

Completion Date

April 2019

Primary Completion Date

April 2018

Eligibility Criteria

        Inclusion Criteria:

          -  Patient has histologically/cytologically confirmed, non-keratinizing/undifferentiated,
             EBV-related nasopharyngeal carcinoma, not amenable to curative intent therapy. EBV
             testing may be completed per institutional standards.

          -  Patient must have at least one measurable site of disease as defined by RECIST v1.1,
             determined by investigator review

          -  Patient has received at least one prior line of systemic therapy in the
             recurrent/metastatic setting

          -  Patient is willing to undergo a fresh tumor biopsy (core or excisional) for
             correlative analyses (ie. PD-L1 expression).The study chair may grant exceptions to
             the mandatory biopsy should the treating physician deem that a biopsy is not feasible
             or unsafe for the patient, and archival tissue is available and provided for study
             purposes. A conversation with the study chair is required to obtain an exception.

          -  Patient has adequate organ and marrow function.

          -  Female patient of childbearing potential has a negative serum or urine pregnancy
             within 72 hours prior to receiving the first dose of study medication

        Exclusion Criteria:

          -  Patient is currently receiving or has received another investigational agent within 4
             weeks prior to Day 1 of study.

          -  Patient has received chemotherapy or radiotherapy within 4 weeks prior to Day 1 of
             study. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided
             there is at least one measurable lesion that has not been radiated.

          -  Patient has received prior immunotherapy with inhibitors of PD-1/PD-L1 axis.

          -  Patient has had major surgery or insufficient recovery from surgical-related trauma or
             wound healing within 14 days of Study Day 1.

          -  Patient has had a prior Grade ≥ 3 immune-related adverse event (irAE) while receiving
             any previous immunotherapy agent, or any unresolved irAE > Grade 1.

          -  Patient has a known additional malignancy that is progressing or requires active
             treatment. Exceptions include basal cell carcinoma of the skin or squamous cell
             carcinoma of the skin that has undergone potentially curative therapy or in situ
             cervical cancer.

          -  Patient has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Patients with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least four weeks
             prior to the first dose of trial treatment and any neurologic symptoms have returned
             to baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment. This exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability.

          -  Patient has an active autoimmune disease that has required systemic treatment in the
             past 2 years (i.e. with use of disease modifying agents, corticosteroids or
             immunosuppressive drugs).Patients with vitiligo, Grave's disease, or psoriasis not
             requiring systemic treatment within the past 2 years are not excluded.Replacement
             therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy
             for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
             treatment.

          -  Patient has a diagnosis of immunodeficiency, or is receiving systemic steroid therapy
             (>10mg prednisone daily, or steroid equivalent) or any other form of immunosuppressive
             therapy within 7 days prior to the first dose of avelumab.

          -  Patient has a known history of active TB (Bacillus Tuberculosis).

          -  Patient has a known history of, or any evidence of active, non-infectious pneumonitis.

          -  Patient has a known history of chronic interstitial lung disease.

          -  Patient has an active infection requiring systemic therapy.

          -  Patient is pregnant or breastfeeding, or expecting to conceive or father children
             within the projected duration of the trial.

          -  Patient has known active Hepatitis B infection (defined as presence of HepB sAg and/
             or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or
             known Human Immunodeficiency Virus (HIV). Patients with HIV who have a normal CD4
             count (≥ 200) and an undetectable viral load are not excluded.

          -  Patient has received a live vaccine within 30 days of study Day 1.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Assuntina Sacco, MD, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT02875613

Organization ID

160114

Responsible Party

Sponsor-Investigator

Study Sponsor

Assuntina Sacco, M.D.

Collaborators

 Pfizer

Study Sponsor

Assuntina Sacco, MD, Principal Investigator, University of California Medical Center

Verification Date

August 2019