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Nasopharyngeal CarcinomaPhase 3VANCENCT02578641

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

A Phase 3 study testing autologous EBV specific Cytotoxic T cells and combination IV gemcitabine and IV carboplatin (AUC2) in people with Nasopharyngeal Carcinoma, run by Tessa Therapeutics at 30 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Nasopharyngeal Carcinoma
What is being tested?
autologous EBV specific Cytotoxic T cells and combination IV gemcitabine and IV carboplatin (AUC2)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
330 participants
Where
30 sitesin 5 countries
Study dates
Jul 2014to 28 Feb 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
Show all 22Show fewer
  • 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
  • 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

Trial locations and contacts

30 sites in 5 countries.

30 sites in 5 countries

United States7 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02215

  • Baylor Scott & White

    Dallas, Texas, 75204

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Baylor College of Medicine

    Houston, Texas, 77030

  • University of California Davis Health

    Sacramento, California, 95817

  • UCSF HDF Comprehensive Cancer Center

    San Francisco, California, 94143

  • Stanford Cancer Center

    Stanford, California, 94305

Other trials in United States

Malaysia7 sites

  • Site MY-03

    George Town, Pulau Pinang

  • Site MY-06

    George Town, Pulau Pinang

  • Site MY-07

    Johor Bahru

  • Site MY-01

    Kuala Lumpur

  • Site MY-04

    Kuala Lumpur

  • Site MY-05

    Kuala Lumpur

  • Site MY-08

    Kuala Lumpur

Other trials in Malaysia

Taiwan7 sites

  • Changhua Christian Hospital

    Changhua

  • Kaohsiung Chang Gung Memorial Hospital

    Kaohsiung City

  • China Medical University Hospital

    Taichung

  • Taichung Veterans General Hospital

    Taichung

  • National Taiwan University Hospital

    Taipei

  • Taipei Veterans General Hospital

    Taipei

  • Linkou Chang Gung Memorial Hospital

    Taoyuan

Other trials in Taiwan

Thailand7 sites

  • Site TH-42

    Bangkok

  • Site TH-43

    Bangkok

  • Site TH-41

    Chiang Mai

  • Site TH-44

    Khon Kaen

  • Site TH-47

    Lopburi

  • Site TH-45

    Ubon Ratchathani

  • Site TH-46

    Udon Thani

Other trials in Thailand

Singapore2 sites

  • Site SG-11

    Singapore

  • Site SG-12

    Singapore

Other trials in Singapore

About this study

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

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".

Read the 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

Being tested
autologous EBV specific Cytotoxic T cells, combination IV gemcitabine and IV carboplatin (AUC2)
Keywords
Nasopharyngeal Carcinoma (NPC), NPC, immunotherapy, Nasopharyngeal Cancer, Nose Cancer, Cell therapy, Head and Neck Cancer, Cytotoxic T cells, chemotherapy, Epstein-Barr Virus
Medical subject headings
Nasopharyngeal Carcinoma, Nasopharyngeal Neoplasms, Nose Neoplasms, Head and Neck Neoplasms, Epstein-Barr Virus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • autologous EBV specific Cytotoxic T cellsBiological

    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.

  • combination IV gemcitabine and IV carboplatin (AUC2)Drug

    4 cycles for Arm A and 6 cycles for Arm B

Study groups in NCT02578641
Study groupRoleWhat they receive
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 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
Receives: Biological: autologous EBV specific Cytotoxic T cells; Drug: 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.
Receives: Drug: combination IV gemcitabine and IV carboplatin (AUC2)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Progression-free Survival (PFS) of Subjects With Advanced Nasopharyngeal Carcinoma.

    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.

    Measured: 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.

  2. Overall Response Rate (ORR) of Subjects With Advanced Nasopharyngeal Carcinoma.

    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.

    Measured: 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.

  3. Clinical Benefit Rate (CBR) of Subjects With Advanced Nasopharyngeal Carcinoma.

    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.

    Measured: 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.

  4. Best Overall Response (BOR) of Subjects With Advanced Nasopharyngeal Carcinoma.

    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.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2015 (estimated)
  2. Study startJul 2014
  3. Primary completion28 Feb 2022
  4. Study completion28 Feb 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
330 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02578641
Sponsor's protocol ID
FF01
Acronym
VANCE
Status last verified
Jun 2023
First submitted
12 Oct 2015
Last updated
28 Jun 2023
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 39241963

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing autologous EBV specific Cytotoxic T cells and combination IV gemcitabine and IV carboplatin (AUC2) in people with Nasopharyngeal Carcinoma, run by Tessa Therapeutics at 30 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in United States, Malaysia, Taiwan, Thailand, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) of Subjects With Advanced Nasopharyngeal Carcinoma. (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02578641, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2023.

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