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A Phase III Trial Evaluating Chemotherapy and Immunotherapy for Advanced Nasopharyngeal Carcinoma (NPC) Patients

NCT02578641

Description:

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 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 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".

Related Conditions:
  • Nasopharyngeal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Phase III Trial Evaluating Chemotherapy and Immunotherapy for Advanced Nasopharyngeal Carcinoma (NPC) Patients
  • 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(NPC) Patients

Clinical Trial IDs

  • ORG STUDY ID: FF01
  • NCT ID: NCT02578641

Conditions

  • Nasopharyngeal Carcinoma

Interventions

DrugSynonymsArms
autologous EBV specific Cytotoxic T LymphocytesArm A
combination IV gemcitabine and IV carboplatin (AUC2)Arm A

Purpose

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 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 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".

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimental4 cycles of combination IV Gemcitabine (1000 mg/m2) and IV carboplatin (AUC2) on Days 1, 8, 15 every 28 days, followed sequentially by T-cell immunotherapy (2 cycles) of autologous EBV specific Cytotoxic T Lymphocytes every 2 weeks, followed by EBV-specific CTL immunotherapy (4 cycles) every 8 weeks after 6 weeks from the second cycle.
  • autologous EBV specific Cytotoxic T Lymphocytes
  • combination IV gemcitabine and IV carboplatin (AUC2)
Arm BActive Comparator6 cycles of combination IV gemcitabine (1000 mg/m2) and IV carboplatin (AUC2) on Days 1, 8, 15 every 28 days.
  • combination IV gemcitabine and IV carboplatin (AUC2)

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

          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

          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 12 months before screening or at 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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:21 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Prolonging Overall Survival
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:Assess the efficacy of CTL following first line chemotherapy in prolonging Overall Survival (OS) of patients with advanced NPC

Secondary Outcome Measures

Measure:Disease Progression
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:Assess the efficacy of CTL in delaying disease progression (PFS) in patients with advanced NPC
Measure:Overall Response Rate
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:Tumor assessment will be according to RECIST 1.1 criteria. Compare the Overall Response Rate under the 2 treatment arms. This is based on the proportion of individuals who achieve a further response (Complete Response or Partial Response) after immunotherapy using preimmunotherapy imaging as baseline
Measure:Clinical Benefit Rate
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:Compare the Clinical Benefit Rate under the 2 treatment arms.Clinical Benefit rate (CBR) is defined as the proportion of patients who achieve Complete Response, Partial Response, Stable Disease to both chemotherapy and then, for Arm A, to immunotherapy using pre immunotherapy (post cycle 4 chemotherapy) imaging as a baseline. Tumor assessment will be according to RECIST 1.1 criteria.
Measure:Quality of Life of patients
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:Compare the Quality of Life of patients based on EORTC QLQ-C30 under the 2 treatment arms

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tessa Therapeutics

Trial Keywords

  • Nasopharyngeal Carcinoma (NPC)
  • NPC
  • immunotherapy
  • Nasopharyngeal Cancer
  • Nose Cancer
  • Cell therapy
  • Head and Neck Cancer
  • Cytotoxic T Lymphocytes
  • chemotherapy
  • Epstein-Barr Virus

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