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

Head and Neck Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00690872
• Other study ID #: CDR0000577971
• Secondary ID: SINGAPORE-07-27-
• Status: Recruiting
• Phase: Phase 2
• First received: June 4, 2008
• Last updated: June 26, 2009
• Start date: July 2008

Study information

• Verified date: June 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Biological:
• autologous Epstein-Barr virus-specific cytotoxic T lymphocytes

Drug:
• carboplatin

• gemcitabine hydrochloride

Genetic:
• polymerase chain reaction

Other:
• fluorescence activated cell sorting

• immunoenzyme technique

Locations

Country	Name	City	State
Singapore	National Cancer Centre - Singapore	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Centre, Singapore

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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			No
Secondary	Median PFS 2, defined as the time from the start of induction immunotherapy to radiological disease progression or death from any cause			No
Secondary	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			No
Secondary	Clinical benefit rate of immunotherapy, defined as the proportion of patients who achieve CR, PR, or stable disease			No