A Phase III Trial Evaluating Chemotherapy and Immunotherapy for Advanced Nasopharyngeal Carcinoma (NPC) Patients
Condition: Nasopharyngeal Carcinoma
MeSH terms: Carcinoma; Nasopharyngeal Carcinoma
Intervention: autologous EBV specific Cytotoxic T cells; combination IV gemcitabine and IV carboplatin (AUC2)
Intervention description: The CTL line will be prepared by co-cultivation of the irradiated EBV-LCL with patient PBMC. A proportion of peripheral blood will be used to generate EBV specific CTLs.; 4 cycles for Arm A and 6 cycles for Arm B
Intervention MeSH terms: Carboplatin; Gemcitabine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 330.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Nasopharyngeal Carcinoma (NPC); NPC; immunotherapy; Nasopharyngeal Cancer; Nose Cancer; Cell therapy; Head and Neck Cancer; Cytotoxic T cells; chemotherapy; Epstein-Barr Virus

Summary:

      This study is a multi-center, randomized, open label, Phase III clinical trial for advanced
      Nasopharyngeal Carcinoma(NPC) Patients.

      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 cells (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 cells 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 30
      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".
    

Eligibility criteria:

        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 as per RECIST 1.1

          3. Human Immunodeficiency Virus (HIV) negative*

             * Status of HIV must be confirmed via a HIV antibody test or other confirmatory tests
             available within 4 weeks of 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 ≥ 18 years or according to local legal age of consent

         10. Eastern Cooperative Oncology Group Performance Scale (ECOG-PS) ≤2

         11. Written informed consent

         12. Life expectancy >6 months

        Key Exclusion Criteria

          1. 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

          2. HIV Positive*

             * Status of HIV must be confirmed via a HIV antibody test or other confirmatory tests
             available within 4 weeks of screening

          3. Pregnant or lactating females

          4. Refuse of use of contraception during trial (both male and female patients)

          5. Investigational therapy less than one month prior to study entry

          6. Pre-existing peripheral neuropathy (National Cancer Institute Common Terminology
             Criteria for Adverse Events [NCI CTCAE] ≥2)

          7. Central nervous system metastasis

          8. 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

          9. Positive hepatitis B surface antigen (HBsAg) results

         10. Known history of hepatitis C and recovery status has not been determined at time of
             screening

         11. Prior anti-cancer treatment for metastatic or locally recurrent disease, EXCEPT:

             For metastatic or locally recurrent disease, localised palliative radiotherapy is
             allowed.

             For locally recurrent disease, the following treatment is allowed

               -  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

        The following is allowable:

        • Adjuvant immunotherapy/ biologics Prior adjuvant immunotherapy/ biologics must be > 6
        months before screening