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

NCT02578641 | Completed Phase 3 Results DMC

• 1 other identifier: FF01
• Study Type: interventional
• Target: 330
• Locations: 5 countries
• Sites: 30

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".

Conditions

Nasopharyngeal Carcinoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) of Subjects With Advanced Nasopharyngeal Carcinoma.

  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.

  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.

Secondary Outcomes (4)

• 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.

• 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.

• 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.

• 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.

Study Arms (2)

Arm A

EXPERIMENTAL

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

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

Arm B

ACTIVE COMPARATOR

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)

Interventions

autologous EBV specific Cytotoxic T cells BIOLOGICAL

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.

Arm A

combination IV gemcitabine and IV carboplatin (AUC2) DRUG

4 cycles for Arm A and 6 cycles for Arm B

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Tessa Therapeutics: lead

Study Sites (30)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California Davis Health

Sacramento, California, 95817, United States

Location

UCSF HDF Comprehensive Cancer Center

San Francisco, California, 94143, United States

Location

Stanford Cancer Center

Stanford, California, 94305, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Baylor Scott & White

Dallas, Texas, 75204, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Site MY-03

George Town, Pulau Pinang, Malaysia

Location

Site MY-06

George Town, Pulau Pinang, Malaysia

Location

Site MY-07

Johor Bahru, Malaysia

Location

Site MY-01

Kuala Lumpur, Malaysia

Location

Site MY-04

Kuala Lumpur, Malaysia

Location

Site MY-05

Kuala Lumpur, Malaysia

Location

Site MY-08

Kuala Lumpur, Malaysia

Location

Site SG-11

Singapore, Singapore

Location

Site SG-12

Singapore, Singapore

Location

Changhua Christian Hospital

Changhua, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan

Location

Taichung Veterans General Hospital

Taichung, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Linkou Chang Gung Memorial Hospital

Taoyuan District, Taiwan

Location

Site TH-42

Bangkok, Thailand

Location

Site TH-43

Bangkok, Thailand

Location

Site TH-41

Chiang Mai, Thailand

Location

Site TH-44

Khon Kaen, Thailand

Location

Site TH-47

Lopburi, Thailand

Location

Site TH-45

Ubon Ratchathani, Thailand

Location

Site TH-46

Udon Thani, Thailand

Location

Related Publications (1)

• Toh HC, Yang MH, Wang HM, Hsieh CY, Chitapanarux I, Ho KF, Hong RL, Ang MK, Colevas AD, Sirachainan E, Lertbutsayanukul C, Ho GF, Nadler E, Algazi A, Lulla P, Wirth LJ, Wirasorn K, Liu YC, Ang SF, Low SHJ, Tho LM, Hasbullah HH, Brenner MK, Wang WW, Ong WS, Tan SH, Horak I, Ding C, Myo A, Samol J. Gemcitabine, carboplatin, and Epstein-Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial. Ann Oncol. 2024 Dec;35(12):1181-1190. doi: 10.1016/j.annonc.2024.08.2344. Epub 2024 Sep 4.

  PMID: 39241963 DERIVED

Related Links

• Sponsor

MeSH Terms

Conditions

Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nose Neoplasms; Head and Neck Neoplasms; Epstein-Barr Virus Infections

Interventions

Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Skull Neoplasms; Bone Neoplasms; Bone Diseases; Musculoskeletal Diseases; Nose Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Khong-Bee Kang, Senior Manager Clinical Development
• Organization: Tessa Therapeutics

kangkhongbee@tessacell.com

+65 6978 6594

Study Officials

• Han Chong TOH

  National Cancer Centre Singapore (NCCS)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2015
• First Posted: October 19, 2015
• Study Start: July 1, 2014
• Primary Completion: February 28, 2022
• Study Completion: February 28, 2022
• Last Updated: June 28, 2023
• Results First Posted: June 28, 2023

Record last verified: 2023-06

Locations

US (7); TW (7); MY (7); TH (7); SG (2)