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Eligibility
for people ages 21 years and up
Location
at San Francisco, California and other locations
Dates
study started
estimated completion:
Principal Investigator

Description

Summary

This study is a multi-center, randomized, open label, Phase III clinical trial. Drugs used in chemotherapy, such as gemcitabine and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving an infusion of a person's cytotoxic T lymphocytes (CTL) that have been treated in the laboratory may help the body build an effective immune response to kill tumor cells. Giving combination chemotherapy together with laboratory-treated T lymphocytes may kill more tumor cells. This Phase III trial is to assess if combined gemcitabine-carboplatin (GC) followed by adoptive T-cell therapy would improve clinical outcome for patients with advanced nasopharyngeal carcinoma (NPC). It is also the world's first, and largest, Phase 3 T-cell therapy cancer trial ever conducted, and enrollment is ongoing for 330 patients from 29 hospital centers across Asia and the United States. This clinical trial is conducted on the back of a successful Phase 2 NPC trial involving 38 patients at the National Cancer Centre, Singapore. This trial produced the best published 2-year (62.9%), and median overall survival (OS) data (29.9 months) in 35 patients with advanced NPC who received autologous EBV-specific CTL. Kindly see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978790/ for the Phase 2 publication titled "Adoptive T-cell Transfer and Chemotherapy in the First line treatment of Metastatic and/or Locally Recurrent Nasopharyngeal Carcinoma".

Official Title

A Multicentre, Randomized, Open-Label, Phase III Clinical Trial Of Gemcitabine And Carboplatin Followed By Epstein-Barr Virus-Specific Autologous Cytotoxic T Lymphocytes Versus Gemcitabine And Carboplatin As First Line Treatment For Advanced Nasopharyngeal Carcinoma Patients

Details

330 patients will be randomized after their eligibility status has been fully determined and informed consent has been obtained. Patients will be randomly allocated to receive either Arm A (Gemcitabine and Carboplatin (GC) x 4 cycles and EBV-specific CTL) or Arm B (GC x 6 cycles alone) in a 1:1 ratio using a stratified block randomization scheme. The stratification variables are country and disease stage (metastatic vs locally recurrent)

After randomization, patients in Arm A will have their peripheral blood taken for the establishment of cytotoxic T cell line and EBV transformed lymphoblastoid cell line (CTL). Within two weeks of enrollment, patients will commence combination GC chemotherapy for a total of 4 cycles. Patients in Stage 2 of study will receive the EBV-specific CTL immunotherapy.

Keywords

Nasopharyngeal Cancer Nasopharyngeal Carcinoma Epstein-Barr Virus Cell therapy Cytotoxic T Lymphocytes Gemcitabine Carboplatin

Eligibility

For people ages 21 years and up

Key Inclusion Criteria

  1. Metastatic or locally recurrent EBV-positive, non-keratinizing and/ or undifferentiated NPC* who do not have curative options such as chemo-radiation or surgery

    *Subjects will be enrolled based on confirmed histology diagnosis of the NPC

  2. Radiologically measurable disease
  3. Human Immunodeficiency Virus (HIV) negative*

    • Status of HIV must be confirmed via a HIV antibody test or other confirmatory tests available within 12 months before screening or at screening
  4. Bilirubin <2 x upper limit of normal (ULN) and aspartate aminotransferase (AST),alanine aminotransferase (ALT) <3 x ULN
  5. Calculated creatinine clearance (CRCL) ≥40 mL/min. Glomerular Filtration Rate (GFR)is calculated based on Cockcroft-Gault method.
  6. Normal corrected calcium levels
  7. Absolute neutrophil count>1200/mm3, hemoglobin (Hb) ≥10 g/dL and platelets≥100,000/mm3
  8. Male or female
  9. Age ≥21 years
  10. Eastern Cooperative Oncology Group Performance Scale (ECOG-PS) ≤2
  11. Written informed consent
  12. Life expectancy>6 months

    Key Exclusion Criteria

  13. Severe concomitant illness i.e. chronic obstructive pulmonary disease (COPD),ischemic heart disease (IHD), active congestive cardiac failure (CCF), active angina pectoris, uncontrolled arrhythmia, uncontrolled hypertension
  14. HIV Positive*

    • Status of HIV must be confirmed via a HIV antibody test or other confirmatory tests available within 12 months before screening or at screening
  15. Pregnant or lactating females
  16. Refuse of use of contraception during trial (both male and female patients)
  17. Investigational therapy less than one month prior to study entry
  18. Pre-existing peripheral neuropathy (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] ≥2)
  19. Central nervous system metastasis
  20. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis and T1] or any cancer curatively treated>3 years prior to study entry
  21. Positive hepatitis B surface antigen (HBsAg) results
  22. Known history of hepatitis C and recovery status has not been determined at time of screening
  23. Prior chemotherapy for metastatic or locally recurrent disease

Exceptions:

  • Prior radiotherapy with curative intent
  • Prior chemo-radiotherapy with curative intent
  • Adjuvant chemotherapy
  • Localised palliative radiotherapy Prior chemotherapy must be> 6 months before screening 12) Severe intercurrent infections 13) Prior immunotherapy for metastatic or locally recurrent disease

Exception:

• Adjuvant immunotherapy/ biologics

Locations

  • Stanford Cancer Center not yet accepting patients
    Stanford, California, 94305, United States
  • City of Hope National Medical Center accepting new patients
    Duarte, California, 91010, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Tessa Therapeutics
Links
Sponsor
ID
NCT02578641
Phase
Phase 3
Lead Scientist
Alain Algazi
Study Type
Interventional
Last Updated
May 1, 2017
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