Head and Neck CancerPhase 2NCT00690872
Gemcitabine and Carboplatin Followed By Laboratory-Treated T Lymphocytes in Treating Patients With Metastatic or Locally Recurrent Epstein-Barr Virus-Positive Nasopharyngeal Cancer
A Phase 2 study testing autologous Epstein-Barr virus-specific cytotoxic T lymphocytes, carboplatin and gemcitabine hydrochloride in people with Head and Neck Cancer, run by National Cancer Centre, Singapore at 1 site in Singapore.
Trial summary
RATIONALE: 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 21 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- autologous Epstein-Barr virus-specific cytotoxic T lymphocytes, carboplatin and gemcitabine hydrochloride
- How many people
- 35 participants
- Where
- 1 siteSingapore
- Study dates
- Jul 2008to Dec 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Biopsy-proven nasopharyngeal carcinoma (NPC)
- WHO type 2/3 disease
- Metastatic or locally recurrent disease
- Epstein-Barr virus (EBV)-positive disease as confirmed by in situ hybridization assay or PCR amplification for EBV-encoded RNA expression
- Radiologically measurable disease
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy > 3 months
- ANC > 1,200/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 8 g/dL
- Bilirubin < 2 times upper limit of normal (ULN)
- AST and ALT < 3 times ULN
- Creatinine clearance ≥ 40 mL/min
- Corrected calcium normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No concurrent severe illness, including any of the following:
- Chronic obstructive pulmonary disease
- Ischemic heart disease
- Active congestive cardiac failure
- Active angina pectoris
- Uncontrolled arrhythmia
- Uncontrolled hypertension
- No concurrent severe infections
- HIV negative
PRIOR CONCURRENT THERAPY:
- No more than one line of prior chemotherapy for metastatic disease
- No prior gemcitabine hydrochloride
- Prior platinum agents allowed
- At least 1 month since prior investigational therapy
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
National Cancer Centre - Singapore
Singapore, 169610
Toh Han Chong, MD, MBBS, MRCP, 65-6436-8172
About this study
Official title: Phase II Trial Evaluating Efficacy of a Strategy Employing Combination Gemcitabine and Carboplatin Chemotherapy Followed by EBV-Specific Cytotoxic T-Lymphocytes in Patients With Metastatic or Locally Recurrent EBV-Positive Nasopharyngeal Carcinoma
RATIONALE: 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 T lymphocytes 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.
PURPOSE: This phase II trial is studying how well giving gemcitabine and carboplatin together with laboratory-treated T lymphocytes works in treating patients with metastatic or locally recurrent Epstein-Barr virus-positive nasopharyngeal cancer.
Read the detailed description
OBJECTIVES:
Primary
- To determine progression-free survival (PFS 1) of patients with metastatic or locally recurrent Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma treated with gemcitabine hydrochloride and carboplatin followed EBV-specific cytotoxic T-lymphocytes (CTL).
Secondary
- To determine progression-free survival (PFS 2) of these patients during the immunotherapy portion of this study.
- To determine the clinical benefit rate of EBV-specific CTL in these patients.
- To determine the tolerability of EBV-specific CTL therapy in these patients.
- To demonstrate persistence of EBV-specific immune response in these patients.
OUTLINE: Patients undergo collection of peripheral blood mononuclear cells (PBMC) from which T cells are purified, co-cultured with irradiated autologous Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTLs), and expanded in vitro for the establishment of cytotoxic T-cell lines.
- Chemotherapy: Patients receive gemcitabine hydrochloride IV over 30 minutes and carboplatin IV over 60 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of course 2, patients undergo evaluation for response. Patients with progressive disease proceed directly to induction immunotherapy. Patients with stable disease (SD), partial response (PR), or complete response (CR) receive 2 additional courses of chemotherapy and then proceed to induction immunotherapy.
- Induction immunotherapy: Beginning 14-28 days after the completion of chemotherapy, patients receive EBV-specific CTLs IV over 1-10 minutes on days 1 and 14. Six weeks after the second infusion, patients undergo evaluation for response. Patients who demonstrate clinical benefit (i.e., CR, PR, SD) to induction immunotherapy proceed to maintenance immunotherapy.
- Maintenance immunotherapy: Patients receive EBV-specific CTLs IV over 1-10 minutes. Treatment repeats every 1-3 months for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection at baseline and prior to each course of induction immunotherapy and maintenance immunotherapy. Samples are analyzed for EBV CTL frequency by immune function assays (i.e., tetramer analysis, enzyme-linked immunospot, and cytotoxic T-lymphocyte precursor assays); for specificity of response by cytotoxicity assays (in patients for whom the appropriate reagents are available); and for evaluation of EBV DNA by polymerase chain reaction. In addition, T-cells are isolated from blood samples for fluorescence-activated cell sorter analysis and for extraction of RNA.
After completion of study therapy, patients are followed at least every 2 months until disease progression.
- Conditions
- Head and Neck Cancer
- Being tested
- autologous Epstein-Barr virus-specific cytotoxic T lymphocytes, carboplatin, gemcitabine hydrochloride, polymerase chain reaction, fluorescence activated cell sorting
- Keywords
- recurrent lymphoepithelioma of the nasopharynx, recurrent squamous cell carcinoma of the nasopharynx, stage IV lymphoepithelioma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
autologous Epstein-Barr virus-specific cytotoxic T lymphocytesBiological
carboplatinDrug
polymerase chain reactionGenetic
fluorescence activated cell sortingOther
immunoenzyme techniqueOther
What is being measured
The primary outcome is the main question the study is designed to answer.
Median progression-free survival (PFS 1), defined as the time from study enrollment to the time of radiological disease progression or death from any cause
Secondary outcomes (3)
Median PFS 2, defined as the time from the start of induction immunotherapy to radiological disease progression or death from any cause
Response rate, defined as the proportion of patients who achieve a complete response (CR) or partial response (PR) after 4 courses of chemotherapy and the proportion of patients who achieve a further response after immunotherapy
Clinical benefit rate of immunotherapy, defined as the proportion of patients who achieve CR, PR, or stable disease
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2008 (estimated)
- Study startJul 2008
- Primary completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Centre, Singapore
- Sponsor type
- University, hospital or other
- Investigators
- Toh Han Chong, MD, MBBS, MRCP, Principal investigator, National Cancer Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00690872
- Sponsor's protocol ID
- CDR0000577971
- Other IDs
- SINGAPORE-07-27-NPC
- Status last verified
- Jun 2009
- First submitted
- 4 Jun 2008
- Last updated
- 29 Jun 2009
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial Evaluating Efficacy of a Strategy Employing Combination Gemcitabine and Carboplatin Chemotherapy Followed by EBV-Specific Cytotoxic T-Lymphocytes in Patients With Metastatic or Locally Recurrent EBV-Positive Nasopharyngeal Carcinoma
- ClinicalTrials.gov ID
- NCT00690872
- Acronym / sponsor ID
- CDR0000577971
- Conditions
- Head and Neck Cancer
- Keywords
- recurrent lymphoepithelioma of the nasopharynx, recurrent squamous cell carcinoma of the nasopharynx, stage IV lymphoepithelioma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- National Cancer Centre, SingaporeUniversity, hospital or other
- Study start
- Jul 2008
- Primary completion
- Dec 2014 (estimated)
- First posted
- 5 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: 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 T lymphocytes 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.
PURPOSE: This phase II trial is studying how well giving gemcitabine and carboplatin together with laboratory-treated T lymphocytes works in treating patients with metastatic or locally recurrent Epstein-Barr virus-positive nasopharyngeal cancer.
Detailed description
OBJECTIVES:
Primary
- To determine progression-free survival (PFS 1) of patients with metastatic or locally recurrent Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma treated with gemcitabine hydrochloride and carboplatin followed EBV-specific cytotoxic T-lymphocytes (CTL).
Secondary
- To determine progression-free survival (PFS 2) of these patients during the immunotherapy portion of this study.
- To determine the clinical benefit rate of EBV-specific CTL in these patients.
- To determine the tolerability of EBV-specific CTL therapy in these patients.
- To demonstrate persistence of EBV-specific immune response in these patients.
OUTLINE: Patients undergo collection of peripheral blood mononuclear cells (PBMC) from which T cells are purified, co-cultured with irradiated autologous Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTLs), and expanded in vitro for the establishment of cytotoxic T-cell lines.
- Chemotherapy: Patients receive gemcitabine hydrochloride IV over 30 minutes and carboplatin IV over 60 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of course 2, patients undergo evaluation for response. Patients with progressive disease proceed directly to induction immunotherapy. Patients with stable disease (SD), partial response (PR), or complete response (CR) receive 2 additional courses of chemotherapy and then proceed to induction immunotherapy.
- Induction immunotherapy: Beginning 14-28 days after the completion of chemotherapy, patients receive EBV-specific CTLs IV over 1-10 minutes on days 1 and 14. Six weeks after the second infusion, patients undergo evaluation for response. Patients who demonstrate clinical benefit (i.e., CR, PR, SD) to induction immunotherapy proceed to maintenance immunotherapy.
- Maintenance immunotherapy: Patients receive EBV-specific CTLs IV over 1-10 minutes. Treatment repeats every 1-3 months for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection at baseline and prior to each course of induction immunotherapy and maintenance immunotherapy. Samples are analyzed for EBV CTL frequency by immune function assays (i.e., tetramer analysis, enzyme-linked immunospot, and cytotoxic T-lymphocyte precursor assays); for specificity of response by cytotoxicity assays (in patients for whom the appropriate reagents are available); and for evaluation of EBV DNA by polymerase chain reaction. In addition, T-cells are isolated from blood samples for fluorescence-activated cell sorter analysis and for extraction of RNA.
After completion of study therapy, patients are followed at least every 2 months until disease progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| autologous Epstein-Barr virus-specific cytotoxic T lymphocytes | Biological | – |
| carboplatin | Drug | – |
| gemcitabine hydrochloride | Drug | – |
| polymerase chain reaction | Genetic | – |
| fluorescence activated cell sorting | Other | – |
| immunoenzyme technique | Other | – |
Primary outcome
Median progression-free survival (PFS 1), defined as the time from study enrollment to the time of radiological disease progression or death from any cause
3 secondary outcomes
Median PFS 2, defined as the time from the start of induction immunotherapy to radiological disease progression or death from any cause
Response rate, defined as the proportion of patients who achieve a complete response (CR) or partial response (PR) after 4 courses of chemotherapy and the proportion of patients who achieve a further response after immunotherapy
Clinical benefit rate of immunotherapy, defined as the proportion of patients who achieve CR, PR, or stable disease
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Toh Han Chong, MD, MBBS, MRCP principal investigator
National Cancer Centre, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing autologous Epstein-Barr virus-specific cytotoxic T lymphocytes, carboplatin and gemcitabine hydrochloride in people with Head and Neck Cancer, run by National Cancer Centre, Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: status not confirmed, as of the sponsor's last update on 29 Jun 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median progression-free survival (PFS 1), defined as the time from study enrollment to the time of radiological disease progression or death from any cause. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jun 2009.