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Multicentre, Randomized, Open-Label, Phase III Clinical Trial for Advanced Nasopharyngeal Carcinoma Patients

This study is currently recruiting participants.
Verified October 2017 by Tessa Therapeutics
Sponsor:
ClinicalTrials.gov Identifier:
NCT02578641
First Posted: October 19, 2015
Last Update Posted: October 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Tessa Therapeutics
  Purpose

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".


Condition Intervention Phase
Nasopharyngeal Cancer Biological: autologous EBV specific Cytotoxic T Lymphocytes Drug: combination IV gemcitabine and IV carboplatin (AUC2) Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Tessa Therapeutics:

Primary Outcome Measures:
  • Prolonging Overall Survival [ Time Frame: through study completion, an average of 1 year ]
    Assess the efficacy of CTL following first line chemotherapy in prolonging Overall Survival (OS) of patients with advanced NPC


Secondary Outcome Measures:
  • Disease Progression [ Time Frame: through study completion, an average of 1 year ]
    Assess the efficacy of CTL in delaying disease progression (PFS) in patients with advanced NPC

  • Overall Response Rate [ Time Frame: through study completion, an average of 1 year ]
    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

  • Clinical Benefit Rate [ Time Frame: through study completion, an average of 1 year ]
    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.

  • Quality of Life of patients [ Time Frame: through study completion, an average of 1 year ]
    Compare the Quality of Life of patients based on EORTC QLQ-C30 under the 2 treatment arms


Estimated Enrollment: 330
Study Start Date: July 2014
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
4 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.
Biological: autologous EBV specific Cytotoxic T Lymphocytes
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.
Drug: combination IV gemcitabine and IV carboplatin (AUC2)
4 cycles for Arm A and 6 cycles for Arm B
Active Comparator: Arm B
6 cycles of combination IV gemcitabine (1000 mg/m2) and IV carboplatin (AUC2) on Days 1, 8, 15 every 28 days.
Drug: combination IV gemcitabine and IV carboplatin (AUC2)
4 cycles for Arm A and 6 cycles for Arm B

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02578641


Contacts
Contact: PAULINE HOON Director, Regulatory Affairs 65 6384 0755 clinicaltrials@tessatherapeutics.com

Locations
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
University of California Davis Health Not yet recruiting
Sacramento, California, United States, 95817
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Stanford Cancer Center Not yet recruiting
Stanford, California, United States, 94305
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02215
United States, Texas
Baylor Research Institute Recruiting
Dallas, Texas, United States, 75204
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Catherine Robertson    832-824-4594    csrobert@txch.org   
Principal Investigator: Premal Lulla, MBBS         
Malaysia
Site MY-07 Recruiting
Johor Bahru, Malaysia
Site MY-01 Recruiting
Kuala Lumpur, Malaysia
Site MY-04 Recruiting
Kuala Lumpur, Malaysia
Site MY-05 Recruiting
Kuala Lumpur, Malaysia
Site MY-08 Recruiting
Kuala Lumpur, Malaysia
Site MY-03 Recruiting
Penang, Malaysia
Site MY-06 Recruiting
Penang, Malaysia
Singapore
Site SG-11 Recruiting
Singapore, Singapore
Site SG-12 Recruiting
Singapore, Singapore
Taiwan
Changhua Christian Hospital Recruiting
Changhua, Taiwan
Kaohsiung Chang Gung Memorial Hospital Not yet recruiting
Kaohsiung, Taiwan
China Medical University Hospital Recruiting
Taichung, Taiwan
Taichung Veterans General Hospital Recruiting
Taichung, Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan
Taipei Veterans General Hospital Recruiting
Taipei, Taiwan
Linkou Chang Gung Memorial Hospital Not yet recruiting
Taoyuan, Taiwan
Thailand
Site TH-42 Recruiting
Bangkok, Thailand
Site TH-43 Recruiting
Bangkok, Thailand
Site TH-41 Recruiting
Chiang Mai, Thailand
Site TH-44 Recruiting
Khon Kaen, Thailand
Site TH-47 Recruiting
Lopburi, Thailand
Site TH-45 Recruiting
Ubon Ratchathani, Thailand
Site TH-46 Recruiting
Udon Thani, Thailand
Sponsors and Collaborators
Tessa Therapeutics
Investigators
Study Chair: Han Chong TOH National Cancer Centre Singapore (NCCS)
  More Information

Additional Information:
Responsible Party: Tessa Therapeutics
ClinicalTrials.gov Identifier: NCT02578641     History of Changes
Other Study ID Numbers: FF01
First Submitted: October 12, 2015
First Posted: October 19, 2015
Last Update Posted: October 5, 2017
Last Verified: October 2017

Keywords provided by Tessa Therapeutics:
Nasopharyngeal Carcinoma
Epstein-Barr Virus
Cell therapy
Cytotoxic T Lymphocytes

Additional relevant MeSH terms:
Carcinoma
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Gemcitabine
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs