Last updated: 07/17/2024 17:38:33
Study to test the efficacy of the vaccine GSK 249553 in treating non-small-cell lung cancer after tumour removal by surgery
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: 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.
Primary purpose:
Prevention
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
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:
Percentage of patients with disease recurrence
Timeframe: At 6, 12, 18, 24 and 30 months after enrolment
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
Number of Participants who Died - Overall Survival (OS)
Timeframe: Over a median follow-up time of 44 months post-Dose 1
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)
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)
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)
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)
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)
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)
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
Number of patients reporting Non-small-cell Lung Cancer (NSCLC) recurrence by gene signature
Timeframe: Over a median follow up time of 86 months
Number of subjects with any and Grade 3 solicited local symptoms
Timeframe: During the 8-day (Days 0-7) post-vaccination period, across doses
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
Number of subjects with any unsolicited adverse events (AEs)
Timeframe: Within the 31-day (Days 0-30) post-vaccination period
Number of subjects with serious adverse events (SAEs)
Timeframe: Throughout the study (Day 0 - Month 86)
Number of subjects with normal and abnormal urinalysis parameters
Timeframe: At Month 6, Month 12, Month 18, Month 24 and Month 30
Number of subjects with normal and abnormal hematological parameters
Timeframe: At Month 6, Month 12, Month 18, Month 24 and Month 30
Number of subjects with normal and abnormal biochemical parameters
Timeframe: At Month 6, Month 12, Month 18, Month 24 and Month 30
Interventions:
Biological/vaccine: GSK 249553 vaccine
Biological/vaccine: Placebo
Enrollment:
182
Observational study model:
Not applicable
Primary completion date:
2011-19-07
Time perspective:
Not applicable
Clinical 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. 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.
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.
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. 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.
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.
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.
Medical condition
Lung Cancer, Non-Small Cell
Product
SB249553
Collaborators
Not applicable
Study date(s)
May 2002 to July 2011
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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.
- 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.
Inclusion and exclusion 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: a) Removal of all gross disease with negative resection margins, by lobectomy, sleeve resection, bilobectomy or pneumonectomy, based on intra-operative findings. b) 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.
Trial location(s)
Location
GSK Investigational Site
Kaiserslautern, Rheinland-Pfalz, Germany, 67655
Status
Study Complete
Location
GSK Investigational Site
Hemer, Nordrhein-Westfalen, Germany, 58675
Status
Study Complete
Location
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
Status
Study Complete
Location
GSK Investigational Site
Udine, Friuli-Venezia-Giulia, Italy, 33100
Status
Study Complete
Location
GSK Investigational Site
Villingen-Schwenningen, Baden-Wuerttemberg, Germany, 78050
Status
Study Complete
Location
GSK Investigational Site
Freiburg, Baden-Wuerttemberg, Germany, 79106
Status
Study Complete
Location
GSK Investigational Site
Grosshansdorf, Schleswig-Holstein, Germany, 22927
Status
Study Complete
Location
GSK Investigational Site
Halle (Saale), Sachsen-Anhalt, Germany, 06114
Status
Study Complete
Location
GSK Investigational Site
Witten, Nordrhein-Westfalen, Germany, 58455
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69126
Status
Study Complete
Location
GSK Investigational Site
Pordenone, Friuli-Venezia-Giulia, Italy, 33170
Status
Study Complete
Location
GSK Investigational Site
Delmenhorst, Niedersachsen, Germany, 27753
Status
Study Complete
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2011-19-07
Actual study completion date
2011-19-07
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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