Clinical Trials /

Reactivating NK Cells in Treating Refractory Head and Neck Cancer

NCT02507154

Description:

This study aims to determine the safety and efficacy of expanded activated autologous NK cells administered after cetuximab in patients with EGFR-positive nasopharyngeal carcinoma or head and neck squamous cell carcinoma.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Nasopharyngeal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Reactivating NK Cells in Treating Refractory Head and Neck Cancer
  • Official Title: Phase I/II Study of Expanded, Activated Autologous Natural Killer Cell Infusions With Cetuximab for Patients With EGFR-Positive Nasopharyngeal Carcinoma or Head and Neck Squamous Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: NK0906
  • NCT ID: NCT02507154

Conditions

  • Nasopharyngeal Cancer
  • Head and Neck Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
Cetuximab + NK cellsErbituxCetuximab + NK cells

Purpose

This study aims to determine the safety and efficacy of expanded activated autologous NK cells administered after cetuximab in patients with EGFR-positive nasopharyngeal carcinoma or head and neck squamous cell carcinoma.

Detailed Description

      Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system that are
      responsible for direct and indirect cytolytic killing of virally-transformed and/or cancer
      cells. Harnessing NK cells in cancer immunotherapy therefore, provides a direct cytotoxic
      effect on cancer cells which further stimulates further downstream adaptive anti-tumor immune
      responses against the cancer. In order to effect a more targeted killing of these tumor
      cells, using a monoclonal antibody (mAb) to direct these NK cells to the target site is
      feasible, provided a specific tumor antigen can be identified. In nasopharyngeal Carcinoma
      (NPC) and head and neck squamous cell carcinoma (HNSCC) where epidermal growth factor
      receptor (EGFR) is ubiquitously expressed, combining NK cell therapy with cetuximab (a
      chimeric mouse/human anti-EGFR monoclonal antibody) to direct these NK cells against these
      EGFR tumor targets is possible. In this study, we seek to enhance the antitumor activity of
      cetuximab to treat EGFR-positive head and neck cancers by combing infusion of activated
      expanded autologous NK cells with cetuximab. Patients selected for this trial are those with
      refractory NPC and HNSCC where no feasible therapeutic options are available. This is a
      lead-in phase I followed by a phase II study. The phase I study will enroll 9 patients and
      will test the feasibility and safety of this combination strategy and determine the tolerated
      dose of NK cell infusion (1x1^06/kg or 1x10^7/kg NK cells) in adult EGFR positive NPC and
      HNSCC patients. For the first 3 patients, each new patient will only be enrolled at least 3
      weeks after treatment of the preceding patient to allow sufficient time to monitor
      toxicities. Initial phase of treatment consists of 7 weeks of cetuximab monotherapy. At week
      8, clinical evaluation will be done to determine patients who are suitable to continue this
      study with NK cell therapy, based on the severity of toxicities encountered. Eligible
      patients will undergo apheresis (Day -10) to harvest NK cells. The collected NK cells will be
      expanded and activated in the laboratory. During cycle 1, cetuximab will be given on day 1
      with subcutaneous IL-2 (three times per week for 2 weeks); followed by expanded NK cells on
      day 2. The purpose of IL-2 is to sustain activity of these NK cells in-vivo. Cetuximab will
      be administered weekly for additional 2 weeks following the NK cell infusion during cycle 1.
      For cycle 2 and 3, cetuximab monotherapy will be administered every 21 days. Clinical
      evaluation will be performed upon completion of cycle 3. Patients with stable disease or with
      partial response will be allowed to continue with a second NK infusion dose as per cycle 1,
      followed by additional 2 more cycles of cetuximab monotherapy (every 21 days).

      .
    

Trial Arms

NameTypeDescriptionInterventions
Cetuximab + NK cellsExperimentalDuring cycle 1, patient will receive intravenous cetuximab and subcutaneous IL-2 on day 1, followed by NK cell infusion on day 2, with subcutaneous IL-2 for an additional 5 doses three times a week to support NK cell viability and expansion in vivo. Following NK cell infusion, cetuximab will be administered weekly for another 2 weeks. During cycle 2 and 3, one cycle of cetuximab monotherapy will be administered 3 weeks apart. Patients who demonstrate objective tumor response or stable disease after cycle 3 will receive a second infusion of NK cells along with cetuximab during cycle 4 therapy at the same dose and schedule as in cycle 1. This will be followed by 2 additional cycles of cetuximab monotherapy (3 weeks apart).
  • Cetuximab + NK cells

Eligibility Criteria

        Inclusion Criteria

          1. Age >21

          2. Histologically confirmed diagnosis of EGFR-positive nasopharyngeal carcinoma or EGFR
             positive HNSCC (based on >80% immunohistochemistry of biopsy of recurrent tumor
             Ventana (Roche) clone 3C6

          3. Recurrent cancer that is not surgically salvageable

          4. Metastatic disease (after one course of palliative chemotherapy has been completed)

          5. Presence of measurable tumor by RECIST 1.1 criteria

          6. At least two weeks since receipt of any biological therapy, chemotherapy, and/or
             radiation

          7. Adequate organ function

          8. Haemoglobin ≥ 9g/dL ANC ≥ 1500/µL Platelet count ≥ 100,000/µL Creatinine clearance
             ≥60ml/minute Total bilirubin ≤ 1.5 x upper limit normal (ULN) AST ≤ 5 x upper limit
             normal ALT ≤ 2 x upper limit normal INR and PTT <1.5 x upper limit normal (ULN)

          9. ECOG performance status of 0-2

         10. Life expectancy of at least 60 days

         11. Localized radiotherapy for palliative pain management is permissible

         12. Written consent to participate on study

         13. Physiological dose of steroid replacement is permissible

        Exclusion Criteria

          1. Treatment within the last 30 days with any investigational drug

          2. Hypersensitivity to cetuximab or any excipients of the NK cell product

          3. Concurrent administration of any other tumor therapy, including cytotoxic
             chemotherapy, hormonal therapy, and immunotherapy

          4. Major surgery within 28 days of study drug administration

          5. Radiotherapy to the target lesions during study or within 3 weeks prior to study
             treatment.

          6. Autologous bone marrow transplant

          7. Active infection that in the opinion of the investigator would compromise the
             patient's ability to tolerate therapy

          8. Lactating or pregnant

          9. Unwilling to use adequate barrier contraception measures during study period.

         10. Second primary malignancy that is clinically detectable at the time of consideration
             for study enrolment

         11. Receipt of immunosuppressives or steroids (=1mg/kg) during time period of 3 days prior
             to expanded NK cell infusion to 30 days after infusion (i.e. day -3 to day +30).

         12. Symptomatic brain metastases

         13. Electrocardiogram with clinically significant findings.

         14. Serious concomitant disorders that would compromise the safety of the patient or
             compromise the patient's ability to complete the study, at the discretion of the
             investigator; serious cardiac illness or medical conditions including but not limited
             to:

               -  Patients with dyspnea at rest.

               -  History of documented congestive heart failure

               -  High risk uncontrolled arrhythmias

               -  Angina pectoris requiring a medicinal product

               -  Clinically significant valvular disease

               -  Poorly controlled hypertension
      
Maximum Eligible Age:N/A
Minimum Eligible Age:21 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety as measured by clinical examination including hematology, renal and liver function tests, adverse events and any significant biochemical abnormalities or toxicities
Time Frame:12- 18 weeks
Safety Issue:
Description:During cycle 1 (21 days) and for at least 21 days following a second NK cell infusion if administered, patients will be reviewed twice a week. Clinical examination including hematology, renal and liver function tests will be performed. Any adverse events (using NCI CTC grading) and concomitant medications notation will be recorded. Any significant biochemical abnormalities or toxicities will be monitored till resolution of these findings or 30 days after patient withdraws from this study, whichever occurs later. During cycles with cetuximab monotherapy, patients with be reviewed once every cycle (21 days).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National University Hospital, Singapore

Trial Keywords

  • cetuximab
  • NK cells
  • nasopharyngeal cancer
  • head and neck squamous cell cancer

Last Updated

August 20, 2018