A Phase III Trial Evaluating Chemotherapy and Immunotherapy for Advanced Nasopharyngeal Carcinoma (NPC) Patients
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| ClinicalTrials.gov Identifier: NCT02578641 |
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Recruitment Status :
Recruiting
First Posted : October 19, 2015
Last Update Posted : August 8, 2019
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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".
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Nasopharyngeal Carcinoma | Biological: autologous EBV specific Cytotoxic T cells Drug: combination IV gemcitabine and IV carboplatin (AUC2) | Phase 3 |
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). *Additional 1-2 chemotherapy cycles (up to total 6 chemo cycles) might be given upon discretion of Investigator, if EBV-specific CTL infusions are not available in time for the 1st scheduled infusion.
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 330 participants |
| 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(NPC) Patients |
| Study Start Date : | July 2014 |
| Estimated Primary Completion Date : | December 2020 |
| Estimated Study Completion Date : | January 2023 |
| Arm | Intervention/treatment |
|---|---|
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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 cells every 2 weeks, followed by EBV-specific CTL immunotherapy (4 cycles) every 8 weeks after 6 weeks from the second cycle. *Additional 1-2 chemotherapy cycles (up to total 6 chemo cycles) might be given upon discretion of Investigator, if EBV-specific CTL infusions are not available in time for the 1st scheduled infusion. |
Biological: autologous EBV specific Cytotoxic T cells
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 |
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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.
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Drug: combination IV gemcitabine and IV carboplatin (AUC2)
4 cycles for Arm A and 6 cycles for Arm B |
- 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
- 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
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Key Inclusion Criteria
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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
- Radiologically measurable disease as per RECIST 1.1
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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
- Bilirubin <2 x upper limit of normal (ULN) and aspartate aminotransferase (AST), alanine aminotransferase (ALT) <3 x ULN
- Calculated creatinine clearance (CRCL) ≥40 mL/min. Glomerular Filtration Rate (GFR) is calculated based on Cockcroft-Gault method.
- Normal corrected calcium levels
- Absolute neutrophil count >1200/mm3, hemoglobin (Hb) ≥10 g/dL and platelets ≥100,000/mm3
- Male or female
- Age ≥ 18 years or according to local legal age of consent
- Eastern Cooperative Oncology Group Performance Scale (ECOG-PS) ≤2
- Written informed consent
- Life expectancy >6 months
Key Exclusion Criteria
- 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
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HIV Positive*
* Status of HIV must be confirmed via a HIV antibody test or other confirmatory tests available within 4 weeks of screening
- Pregnant or lactating females
- Refuse of use of contraception during trial (both male and female patients)
- Investigational therapy less than one month prior to study entry
- Pre-existing peripheral neuropathy (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] ≥2)
- Central nervous system metastasis
- 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
- Positive hepatitis B surface antigen (HBsAg) results
- Known history of hepatitis C and recovery status has not been determined at time of screening
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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
- Severe intercurrent infections
- 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
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
| Contact: JOSEMUND MENEZES | 65 6384 0755 | clinicaltrials@tessatherapeutics.com |
| United States, California | |
| City of Hope National Medical Center | Recruiting |
| Duarte, California, United States, 91010 | |
| Contact: Khaleda Khan 626-256-4673 kkhan@coh.org | |
| Principal Investigator: Erminia Massarelli, MD | |
| University of California Davis Health | Recruiting |
| Sacramento, California, United States, 95817 | |
| Contact: Steffany Lim 916-734-0561 sllim@ucdavis.edu | |
| Contact: Patsy Betita-Pasquinelli 916-734-8409 ppasquinelli@ucdavis.edu | |
| Principal Investigator: Mehrdad Abedi, MD | |
| UCSF HDF Comprehensive Cancer Center | Recruiting |
| San Francisco, California, United States, 94143 | |
| Contact: Audrey Humphries 415-502-3569 Audrey.Humphries@ucsf.edu | |
| Principal Investigator: Alain Algazi, MD | |
| Stanford Cancer Center | Recruiting |
| Stanford, California, United States, 94305 | |
| Contact: Elizabeth Winters 650-721-6509 ewinters@stanford.edu | |
| Principal Investigator: Dimitrios A. Colevas, MD | |
| United States, Massachusetts | |
| Massachusetts General Hospital | Recruiting |
| Boston, Massachusetts, United States, 02215 | |
| Contact: Jami L Brown 617-724-9190 Jbrown56@mgh.harvard.edu | |
| Contact: Vasselina Toncheva (617) 726-4270 VTONCHEVA@PARTNERS.ORG | |
| Principal Investigator: Lori J Wirth, MD | |
| United States, Texas | |
| Baylor Scott & White | Recruiting |
| Dallas, Texas, United States, 75204 | |
| Contact: Delia Graham 214-820-5424 Delia.Graham@BSWHealth.org | |
| Principal Investigator: Eric S Nadler, MD | |
| 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-03 | Recruiting |
| George Town, Penang, Malaysia | |
| Site MY-06 | Recruiting |
| George Town, Penang, 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 | |
| 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 | 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 | 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 | |
| Study Chair: | Han Chong TOH | National Cancer Centre Singapore (NCCS) |
Additional Information:
| Responsible Party: | Tessa Therapeutics |
| ClinicalTrials.gov Identifier: | NCT02578641 History of Changes |
| Other Study ID Numbers: |
FF01 |
| First Posted: | October 19, 2015 Key Record Dates |
| Last Update Posted: | August 8, 2019 |
| Last Verified: | August 2019 |
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Nasopharyngeal Carcinoma (NPC) NPC immunotherapy Nasopharyngeal Cancer Nose Cancer |
Cell therapy Head and Neck Cancer Cytotoxic T cells chemotherapy Epstein-Barr Virus |
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Carcinoma Nasopharyngeal Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Nasopharyngeal 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 |