Study to Test the Efficacy of the Vaccine GSK 249553 in Treating Non-small-cell Lung Cancer After Tumour Removal by Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00290355
First received: February 10, 2006
Last updated: April 11, 2013
Last verified: March 2013
  Purpose

Patients will receive injections of GSK 249553 vaccine . Appropriate tests will be performed to assess the safety of the treatment and its ability to induce an immune response.


Condition Intervention Phase
Lung Cancer, Non-Small Cell
Biological: GSK 249553 vaccine
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Phase IIB Study to Assess the Efficacy of GSK 249553 as Adjuvant Therapy Given to MAGE-3-Positive Patients With Non-Small-Cell Lung Cancer in Stage IB (T2/N0) or II (T1/N1 or T2/N1 or T3/N0), Who Have Had Complete Surgical Resection

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of days from surgical resection to the recurrence of NSCLC (all types of recurrence will be included) [ Time Frame: At the time of analysis ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Recurrence [ Time Frame: 6, 12, 18, 24 and 30 months after enrolment ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: At the time of analysis ] [ Designated as safety issue: No ]
  • Time to death [ Time Frame: At the time of analysis ] [ Designated as safety issue: No ]
  • Time to lung cancer death [ Time Frame: At the time of analysis ] [ Designated as safety issue: No ]
  • Lung-cancer-related death [ Time Frame: 30 months after enrolment ] [ Designated as safety issue: No ]
  • Antibodies to MAGE-3 and protein D [ Time Frame: At all points during treatment as specified in the study schedule ] [ Designated as safety issue: No ]
  • In vitro cellular immune response [ Time Frame: At all points during treatment as specified in the study schedule ] [ Designated as safety issue: No ]
  • Serum level of Cyfra21.1 and CEA [ Time Frame: At all points during treatment as specified in the study schedule ] [ Designated as safety issue: No ]
  • Level of plasma DNA and molecular characterisation by loss of heterozygosity and microsatellite instability [ Time Frame: At all points during treatment as specified in the study schedule. ] [ Designated as safety issue: No ]
  • Number of circulating tumour cells in the blood [ Time Frame: At all points during treatment as specified in the study schedule ] [ Designated as safety issue: No ]
  • MAGE-3 expression in circulating tumour cells in the blood [ Time Frame: At all points during treatment as specified in the study schedule ] [ Designated as safety issue: No ]
  • Gene expression profiles of primary and relapsed tumour samples [ Time Frame: At the time of resection ] [ Designated as safety issue: No ]
  • Proteomes of the patients' plasma [ Time Frame: At all points during treatment as specified in the study schedule ] [ Designated as safety issue: No ]
  • Solicited local and general signs and symptoms recorded by the patients on diary cards [ Time Frame: For a period of 7 days following each administration of vaccine/placebo ] [ Designated as safety issue: No ]
  • Unsolicited non-serious adverse events [ Time Frame: Reported at any time until 30 days following the most recent administration of vaccine/placebo ] [ Designated as safety issue: No ]
  • All serious adverse events [ Time Frame: At any time during the study ] [ Designated as safety issue: No ]
  • Haematological, biochemical and urinalysis parameters [ Time Frame: At regular intervals during the study ] [ Designated as safety issue: No ]

Enrollment: 182
Study Start Date: May 2002
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vaccine Group
Not Applicable
Biological: GSK 249553 vaccine
Intramuscular injection, 13 doses
Placebo Comparator: Placebo Group
Not Applicable
Biological: Placebo
Intramuscular administration, 13 doses

Detailed Description:

This Phase IIb study will be conducted at centres in several European countries according to a multicentre, international, randomised, double-blind design. It will provide information about the clinical and immunological efficacy and the tolerability of GSK 249553 when this is administered to patients with stage IB, II NSCLC. The study treatment will be administered by intramuscular injection; first administration will take place 4-6 weeks after surgery. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent has been obtained prior to surgical tumour resection and prior to the performance of any other protocol-specific procedures.
  • At least 18 years of age at the time of resection.
  • Pathologically proven, surgically staged squamous or non-squamous IB, IIA or IIB NSCLC, and complete surgical resection.
  • The operative technique for resection of the patient's tumour involves at least a lobectomy or a sleeve lobectomy, conforming to all of the following criteria:

    1. Removal of all gross disease with negative resection margins, by lobectomy, sleeve resection, bilobectomy or pneumonectomy, based on intra-operative findings.
    2. The level of nodal sampling is at least as follows:

Levels 4, 7, 10 in both right upper and right middle lobes Levels 4, 7, 9, 10 in right lower lobe Levels 5, 6, 7 in left upper lobe Levels 7, 9, 10 in left lower lobe. or at the maximum defined as systematic radical mediastinal lymphadenectomy: all ipsilateral and easily accessible lymph-node levels must be removed, independently of the location of the primary tumour. The level of nodal sampling is as follows: Levels 2, 4, 7, 8, 9, 10 in right-sided tumours, Levels 5, 6, 7, 8, 9, 10 in left-sided tumours

  • Tumour shows expression of MAGE-3 antigen.
  • Recovered from surgery for at least 4 weeks and not more than 6 weeks.
  • ECOG performance status of ≤ 1 at the time of randomisation.
  • Laboratory criteria (all of the following must be fulfilled): adequate bone marrow reserve, adequate renal function, adequate hepatic function, serum bilirubin within normal range, negative HIV antibody test, negative HBV antigen test, negative HCV antibody test.
  • (For females): EITHER not of child-bearing potential OR sexually abstinent OR all of the following: negative urine/serum β-HCG pregnancy test, use of adequate contraceptive precautions for 30 days before first vaccination. Agree to continue such precautions for 2 months after completion of the course of vaccination.

Exclusion Criteria:

  • Received any anti-cancer specific treatment including radiotherapy, prior to surgery, unless the treatment was for previous malignancies allowed by the protocol, i.e., basal and localised squamous-cell skin carcinoma that has been successfully treated, or carcinoma in situ of the cervix (see exclusion criterion no. 10).
  • Candidate for post-surgery radiation therapy or any kind of anti-cancer-specific treatment.
  • Pregnant/lactating.
  • (For female patients of child-bearing potential): not agree to practice an effective method of contraception.
  • Uncontrolled bleeding disorder.
  • Autoimmune disease.
  • History of anaphylaxis or severe allergic reaction.
  • Undergone splenectomy or radiation to the spleen.
  • Received a major organ allograft.
  • Malignancies at other sites (except (i) basal and localised squamous-cell skin carcinoma that has been successfully treated, and (ii) carcinoma in situ of the cervix).
  • Concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
  • Uncontrolled congestive heart failure or hypertension.
  • Unstable heart disease or uncontrolled arrhythmia at the time of enrolment.
  • Psychiatric or addictive disorders that may compromise ability to give informed consent, or to comply with the trial procedures.
  • Any evidence of residual tumour after surgery.
  • Require concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents.
  • Received chemotherapy, immunotherapy related to NSCLC.
  • Need home oxygenation.
  • Received any investigational or non-registered drug or vaccine other than the study vaccine within the 30 days preceding the first dose of study vaccine, or plans to receive such a drug during the study period.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00290355

Locations
Latvia
GSK Investigational Site
Riga, Latvia, LV 1002
GSK Investigational Site
Rigas Rajons, Latvia, LV 2118
Norway
GSK Investigational Site
Oslo, Norway
Poland
GSK Investigational Site
Gdansk, Poland, 80-211
Spain
GSK Investigational Site
Barcelona, Spain, 08036
GSK Investigational Site
Madrid, Spain, 28035
GSK Investigational Site
Oviedo, Spain, 33006
GSK Investigational Site
Santander, Spain, 38008
GSK Investigational Site
Valencia, Spain, 46010
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Passlick B et al. MAGE-A3 Antigen-Specific Cancer Immunotherapeutic (ASCI) as adjuvant therapy in resected stage IB/II Non-Small Cell Lung Cancer (NSCLC): from proof-of-concept to Phase III trial (MAGRIT). Abstract presented at the European Multidisciplinary Conference in Thoracic Oncology (EMCTO), Lugano, Switzerland. 1-3 May 2009; 64 (suppl. 1):S45 (102PD).
Vansteenkiste J et al. Multi-center, double-blind, randomized, placebo-controlled Phase II study to assess the efficacy of recombinant MAGE-A3 vaccine as adjuvant therapy in stage IB/II MAGE-A3-positive, completely resected, Non-Small Cell Lung Cancer (NSCLC). Abstract presented at the 43rd Annual Meeting American Society of Clinical Oncology (ASCO), Chicago, IL. 1-5 June 2007.
Vansteenkiste J et al. Activity of MAGE-A3 cancer immunotherapeutic as adjuvant therapy in stage IB/II Non-Small Cell Lung Cancer (NSCLC): Final results of a multi-center, double-blind, randomized, placebo-controlled Phase II study. Abstract presented at the 12th Conference on Lung Cancer (WCLC), Seoul, Korea. 2-6 September 2007.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00290355     History of Changes
Other Study ID Numbers: 249553/004
Study First Received: February 10, 2006
Last Updated: April 11, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Latvia: Zalu Valsts Agentura
Norway: The Royal Norwegian Ministry of Health and Care Services
Poland: Ministerstwo Zdrowia
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Lithuania: SMCA (State Medicine Control Agency)
Spain: Bernat Soria
Estonia: ERC on Human Research of the University of Tartu
Italy: Comitato Etico IST (Istituto Nazionale per la Ricerca sul Cancro)
Germany: Paul-Ehrlich-Institut
Greece: National Drug Organisation

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 22, 2014