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

Phase 3

Completed

Conditions: Nasopharyngeal Carcinoma

Interventions: Biological: autologous EBV specific Cytotoxic T cells
Drug: combination IV gemcitabine and IV carboplatin (AUC2)

Registration Number: NCT02578641

Lead Sponsor: Tessa Therapeutics

Brief 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".

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). \*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.

As of 1 May 2020, patients who have not received the first infusion of EBV-specific CTLs, will instead continue to receive a total of 6 cycles combination of Gemcitabine (1000 mg/m2) and carboplatin (AUC2) on Days 1, 8, 15 every 28 days

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 330

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	combination IV gemcitabine and IV carboplatin (AUC2)	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. As of 1 May 2020, patients who have not received the first infusion of EBV-specific CTLs, will instead continue to receive a total of 6 cycles combination of Gemcitabine (1000 mg/m2) and carboplatin (AUC2) on Days 1, 8, 15 every 28 days
Arm B	combination IV gemcitabine and IV carboplatin (AUC2)	6 cycles of combination IV gemcitabine (1000 mg/m2) and IV carboplatin (AUC2) on Days 1, 8, 15 every 28 days.
Arm A	autologous EBV specific Cytotoxic T cells	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. As of 1 May 2020, patients who have not received the first infusion of EBV-specific CTLs, will instead continue to receive a total of 6 cycles combination of Gemcitabine (1000 mg/m2) and carboplatin (AUC2) on Days 1, 8, 15 every 28 days

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS) of Subjects With Advanced Nasopharyngeal Carcinoma.	From randomization until death, assessed up to 7 years. Survivors and lost to follow-up subjects were censored at the date of last contact. Survival follow-up was done every 12 weeks from end of treatment.	Efficacy of EBV-CTL following first line chemotherapy was compared to chemotherapy alone in terms of OS of subjects with advanced nasopharyngeal carcinoma. Overall survival was defined as the duration in months from the day of randomization until death from any cause for a subject known to be deceased, or censored at the last contact date that a subject was known to be alive or lost to follow-up.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR) of Subjects With Advanced Nasopharyngeal Carcinoma.	From randomization until End of Treatment, an average of 13 months for the gemcitabine+carboplatin and EBVCTL arm and 6 months for the gemcitabine+carboplatin only arm.	Overall response rate was assessed by sites using computed tomography/magnetic resonance imaging based on RECIST version 1.1, which defined Complete Response (CR) as disappearance of all lesions and pathologic lymph nodes; Partial Response (PR) as \>=30% decrease in the sum of the longest diameter (SLD) of target lesions, no new lesions, no progression of non-target lesions; Stable disease (SD) as no PR and no progressive disease (PD); PD as \>=20% increase SLD compared to smallest SLD or progression of non-target lesions or new lesions. The ORR for each treatment arm was comprised of the proportion of subjects who achieved a best overall response of CR or PR while on treatment (until End of Treatment visit), taking as reference the tumor measurement at baseline. Subjects who achieved CR or PR are responders, otherwise are non-responders.
Clinical Benefit Rate (CBR) of Subjects With Advanced Nasopharyngeal Carcinoma.	From randomization until End of Treatment, an average of 13 months for the gemcitabine+carboplatin and EBVCTL arm and 6 months for the gemcitabine+carboplatin only arm.	Clinical benefit rate (CBR) was assessed using computed tomography/magnetic resonance imaging based on RECIST version 1.1., which defined CR as disappearance of all lesions and pathologic lymph nodes; PR as \>=30% decrease in the sum of the longest diameter (SLD) of target lesions, no new lesions, no progression of non-target lesions; SD as no PR and no PD; PD as \>=20% increase SLD compared to smallest SLD or progression of non-target lesions or new lesions. CBR was defined as the proportion of subjects who achieved CR, PR, or SD while on treatment (until End of Treatment visit), taking as reference the tumor measurement at baseline.
Progression-free Survival (PFS) of Subjects With Advanced Nasopharyngeal Carcinoma.	From randomization until first occurrence of disease progression or death of any cause, whichever occurred first, assessed up to 7 years. Subjects who received subsequent anti-cancer therapy were censored at the date of last tumor assessment.	Progression-free survival was defined as the duration from randomization to the first occurrence of documented disease progression \[based on imaging results\] or death from any cause, whichever occurred first.
Best Overall Response (BOR) of Subjects With Advanced Nasopharyngeal Carcinoma.	From randomization until End of Treatment, an average of 13 months for the gemcitabine+carboplatin and EBVCTL arm and 6 months for the gemcitabine+carboplatin only arm.	Best overall response (BOR) was assessed using computed tomography/magnetic resonance imaging based on RECIST version 1.1., which defined CR as disappearance of all lesions and pathologic lymph nodes; PR as \>=30% decrease in the sum of the longest diameter (SLD) of target lesions, no new lesions, no progression of non-target lesions; SD as no PR and no PD; PD as \>=20% increase SLD compared to smallest SLD or progression of non-target lesions or new lesions. The BOR of each treatment arm consisted of CR, PR, SD, PD, NE, and NA while on treatment (until End of Treatment visit), taking as reference the tumor measurement at baseline. The ORR was comprised of the proportion of subjects who achieved a BOR of CR or PR.

Trial Locations

Locations (30): Site MY-04
🇲🇾
Kuala Lumpur, Malaysia
Taichung Veterans General Hospital
🇨🇳
Taichung, Taiwan
Site TH-45
🇹🇭
Ubon Ratchathani, Thailand
Site MY-03
🇲🇾
George Town, Penang, Malaysia
Site MY-06
🇲🇾
George Town, Penang, Malaysia
Site MY-01
🇲🇾
Kuala Lumpur, Malaysia
Site MY-05
🇲🇾
Kuala Lumpur, Malaysia
Changhua Christian Hospital
🇨🇳
Changhua, Taiwan
Taipei Veterans General Hospital
🇨🇳
Taipei, Taiwan
Site MY-07
🇲🇾
Johor Bahru, Malaysia
Site TH-44
🇹🇭
Khon Kaen, Thailand
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
Site TH-43
🇹🇭
Bangkok, Thailand
Site SG-11
🇸🇬
Singapore, Singapore
City of Hope National Medical Center
🇺🇸
Duarte, California, United States
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Stanford Cancer Center
🇺🇸
Stanford, California, United States
UCSF HDF Comprehensive Cancer Center
🇺🇸
San Francisco, California, United States
University of California Davis Health
🇺🇸
Sacramento, California, United States
Baylor Scott & White
🇺🇸
Dallas, Texas, United States
Site MY-08
🇲🇾
Kuala Lumpur, Malaysia
Site SG-12
🇸🇬
Singapore, Singapore
Kaohsiung Chang Gung Memorial Hospital
🇨🇳
Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳
Taichung, Taiwan
Linkou Chang Gung Memorial Hospital
🇨🇳
Taoyuan, Taiwan
Site TH-41
🇹🇭
Chiang Mai, Thailand
Site TH-42
🇹🇭
Bangkok, Thailand
Site TH-47
🇹🇭
Lopburi, Thailand
Site TH-46
🇹🇭
Udon Thani, Thailand