Clinical trial NCT00290355: Study to Test the Efficacy of the Vaccine GSK 249553 in Treating Non-small-cell Lung Cancer After Tumour Removal by Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer, Non-Small Cell
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-02-13
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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 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.

Primary outcomes:
measure: Number of Patients Reporting Confirmed Non-small-cell Lung Cancer (NSCLC) Recurrence
timeFrame: Over a median follow-up time of 28 months post-Dose 1
Secondary outcomes:
measure: Percentage of Patients With Disease Recurrence
timeFrame: At 6, 12, 18, 24 and 30 months after enrolment
measure: Number of Patients Reporting Confirmed Non-small-cell Lung Cancer (NSCLC) Recurrence or Death - Disease Free Survival (DFS)
timeFrame: Over a median follow-up time of 44 months post-Dose 1
measure: Number of Participants Who Died - Overall Survival (OS)
timeFrame: Over a median follow-up time of 44 months post-Dose 1
measure: Number of Subjects Seropositive Against MAGE-A3
timeFrame: At Day 0, Week 6, Week 12, Month 9, Month 18, Month 24, at Month 30 and at Follow-Up (FU) visit (Post Dose 13 at Month 42 for patients with full treatment course or Post last product dose + 12 months for the other patients)
measure: Anti- MAGE-A3 Antibody Concentrations
timeFrame: At Day 0, Week 6, Week 12, Month 9, Month 18, Month 24, at Month 30 and at Follow-Up (FU) visit (Post Dose 13 at Month 42 for patients with full treatment course or Post last product dose + 12 months for the other patients)
measure: Number of Subjects Seropositive Against Protein D (PD) Antigens
timeFrame: At Day 0, Week 6, Week 12, Month 9, Month 18, Month 24, at Month 30 and at Follow-Up (FU) visit (Post Dose 13 at Month 42 for patients with full treatment course or Post last product dose + 12 months for the other patients)
measure: Anti-protein D (Anti-PD) Antibody Concentrations
timeFrame: At Day 0, Week 6, Week 12, Month 9, Month 18, Month 24, at Month 30 and at Follow-Up (FU) visit (Post Dose 13 at Month 42 for patients with full treatment course or Post last product dose + 12 months for the other patients)
measure: Number of Subjects With Cell-mediated Immunity (CMI) Cluster of Differentiation (CD) 4+ Response
timeFrame: At Week 6, Week 12, Month 9, Month 18, Month 24, at Month 30 and at Follow-Up (FU) visit (Post Dose 13 at Month 42 for patients with full treatment course or Post last product dose + 12 months for the other patients)
measure: Number of Subjects With Cell-mediated Immunity (CMI) Cluster of Differentiation (CD) 8+ Response
timeFrame: At Week 6, Week 12, Month 9, Month 18, Month 24, at Month 30 and at Follow-Up (FU) visit (Post Dose 13 at Month 42 for patients with full treatment course or Post last product dose + 12 months for the other patients)
measure: Number of Subjects With Cell-mediated Immunity (CMI) CD4+ or CD8+ Response
timeFrame: At Week 6, Week 12, Month 9, Month 18, Month 24, at Month 30 and at Month 60
measure: Number of Patients Reporting Non-small-cell Lung Cancer (NSCLC) Recurrence by Gene Signature
timeFrame: Over a median follow up time of 86 months
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 8-day (Days 0-7) post-vaccination period, across doses
measure: Number of Subjects With Any, Grade 2/3/4 and Related Solicited General Symptoms
timeFrame: During the 8-day (Days 0-7) post-vaccination period, across doses
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: Within the 31-day (Days 0-30) post-vaccination period
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Throughout the study (Day 0 - Month 86)
measure: Number of Subjects With Normal and Abnormal Urinalysis Parameters
timeFrame: At Month 6, Month 12, Month 18, Month 24 and Month 30
measure: Number of Subjects With Normal and Abnormal Hematological Parameters
timeFrame: At Month 6, Month 12, Month 18, Month 24 and Month 30
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters
timeFrame: At Month 6, Month 12, Month 18, Month 24 and Month 30
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Edegem
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Pessac
country: France
facility: GSK Investigational Site
city: Rennes Cedex 09
country: France
facility: GSK Investigational Site
city: Freiburg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Heidelberg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Villingen-Schwenningen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Ebensfeld
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Gauting
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Offenbach
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Delmenhorst
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Hemer
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Witten
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Kaiserslautern
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Halle (Saale)
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Halle
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Grosshansdorf
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Bad Berka
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Marousi
country: Greece
facility: GSK Investigational Site
city: Rio-Patras
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Pordenone
country: Italy
facility: GSK Investigational Site
state: Friuli-Venezia-Giulia
city: Udine
country: Italy
facility: GSK Investigational Site
state: Friuli-Venezia-Giulia
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Perugia
country: Italy
facility: GSK Investigational Site
state: Umbria
city: Venezia
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Rigas Rajons
country: Latvia
facility: GSK Investigational Site
city: Riga
country: Latvia
facility: GSK Investigational Site
city: Vilnius
country: Lithuania
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Nijmegen
country: Netherlands
facility: GSK Investigational Site
city: Oslo
country: Norway
facility: GSK Investigational Site
city: Trondheim
country: Norway
facility: GSK Investigational Site
city: Checiny
country: Poland
facility: GSK Investigational Site
city: Gdansk
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Tuszyn
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Zakopane
country: Poland
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: La Coruña
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Oviedo
country: Spain
facility: GSK Investigational Site
city: Palma de Mallorca
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Hull
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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).
citation: 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.
citation: Vansteenkiste J et al. 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 evaluating the MAGE-A3 cancer immunotherapeutic. Abstract presented at The 14th European Cancer Conference (ECCO) (formerly ECCO14/ESTRO 26), Barcelona, Spain. 23-27 September 2007.
citation: 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.
citation: 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 42nd Annual Meeting American Society of Clinical Oncology (ASCO), Atlanta, GA. 2-6 June 2006.
citation: Vansteenkiste J et al. Phase II randomized study of MAGE-A3 immunotherapeutic as adjuvant therapy in stage IB/II Non-Small Cell Lung Cancer (NSCLC): 44 month follow-up, humoral and cellular immune response data. European Society for Medical Oncology (IASLC-ESMO) Abstract presented at the 1st European Lung Cancer Conference (ELCC), Geneva, Switzerland. 23-26 April 2008; 3 (4 suppl.1):S55-56.
citation: Zielinski M 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 17th European Conference on General Thoracic Surgery (ECGTS), Krakow, Poland. 31 May-3 June 2009.
citation: Zhu J, Yuan Y, Wan X, Yin D, Li R, Chen W, Suo C, Song H. Immunotherapy (excluding checkpoint inhibitors) for stage I to III non-small cell lung cancer treated with surgery or radiotherapy with curative intent. Cochrane Database Syst Rev. 2021 Dec 6;12(12):CD011300. doi: 10.1002/14651858.CD011300.pub3.
citation: Vansteenkiste J, Zielinski M, Linder A, Dahabreh J, Gonzalez EE, Malinowski W, Lopez-Brea M, Vanakesa T, Jassem J, Kalofonos H, Perdeus J, Bonnet R, Basko J, Janilionis R, Passlick B, Treasure T, Gillet M, Lehmann FF, Brichard VG. Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase II randomized study results. J Clin Oncol. 2013 Jul 1;31(19):2396-403. doi: 10.1200/JCO.2012.43.7103. Epub 2013 May 28.
citation: Ulloa-Montoya F, Louahed J, Dizier B, Gruselle O, Spiessens B, Lehmann FF, Suciu S, Kruit WH, Eggermont AM, Vansteenkiste J, Brichard VG. Predictive gene signature in MAGE-A3 antigen-specific cancer immunotherapy. J Clin Oncol. 2013 Jul 1;31(19):2388-95. doi: 10.1200/JCO.2012.44.3762. Epub 2013 May 28.