Gemcitabine and Carboplatin Followed By Laboratory-Treated T Lymphocytes in Treating Patients With Metastatic or Locally Recurrent Epstein-Barr Virus-Positive Nasopharyngeal Cancer

This study is currently recruiting participants.
Verified June 2009 by National Cancer Institute (NCI)
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00690872
First received: June 4, 2008
Last updated: June 26, 2009
Last verified: June 2009
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Biological: autologous Epstein-Barr virus-specific cytotoxic T lymphocytes
Drug: carboplatin
Drug: gemcitabine hydrochloride
Genetic: polymerase chain reaction
Other: fluorescence activated cell sorting
Other: immunoenzyme technique
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Median PFS 2, defined as the time from the start of induction immunotherapy to radiological disease progression or death from any cause [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
  • Clinical benefit rate of immunotherapy, defined as the proportion of patients who achieve CR, PR, or stable disease [ Designated as safety issue: No ]

Estimated Enrollment: 35
Study Start Date: July 2008
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00690872

Locations
Singapore
National Cancer Centre - Singapore Recruiting
Singapore, Singapore, 169610
Contact: Toh Han Chong, MD, MBBS, MRCP    65-6436-8172      
Sponsors and Collaborators
National Cancer Centre, Singapore
Investigators
Principal Investigator: Toh Han Chong, MD, MBBS, MRCP National Cancer Centre, Singapore
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00690872     History of Changes
Other Study ID Numbers: CDR0000577971, SINGAPORE-07-27-NPC
Study First Received: June 4, 2008
Last Updated: June 26, 2009
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Gemcitabine
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on April 17, 2014