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

GlaxoSmithKline182 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

182

Conditions

Lung Cancer, Non-Small Cell

Interventions

GSK 249553 vaccineBIOLOGICAL

Intramuscular injection, 13 doses

PlaceboBIOLOGICAL

Intramuscular administration, 13 doses

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (62)

Outcomes

Primary Outcomes

Number of Patients Reporting Confirmed Non-small-cell Lung Cancer (NSCLC) Recurrence

Types of recurrence included local, regional and distant metastasis and second primary lung tumours, and comprised: Local recurrence, defined as a tumour within the same lung or at the bronchial stump; Regional recurrence, involving a clinically or radiologically manifest disease in the mediastinum or in supraclavicular nodes; and Distant recurrence, i.e., any tumour arising in the contralateral lung or outside the hemithorax. The time to recurrence was defined as the interval from the date of surgical resection to the date of recurrence. The latter was defined as the date of the first study assessment at which new lesion(s) were found and confirmed by appropriate imaging.

Time frame: Over a median follow-up time of 28 months post-Dose 1

Secondary Outcomes

Percentage of Patients With Disease Recurrence

Time frame: 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)

Data from ClinicalTrials.gov

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GSK Investigational Site

Brussels, Belgium

GSK Investigational Site

Edegem, Belgium

GSK Investigational Site

Ghent, Belgium

GSK Investigational Site

Leuven, Belgium

GSK Investigational Site

Tallinn, Estonia

GSK Investigational Site

Tartu, Estonia

GSK Investigational Site

Helsinki, Finland

GSK Investigational Site

Tampere, Finland

GSK Investigational Site

Pessac, France

GSK Investigational Site

Rennes, France

...and 52 more locations

Time frame: Over a median follow-up time of 44 months post-Dose 1

Number of Participants Who Died - Overall Survival (OS)

Overall Survival (OS) was based on total number of deaths, irrespective of cause of death. Non-small-cell Lung Cancer Overall Survival (NSCLC-OS) was based on total number of deaths due to lung cancer; deaths due to other or to unknown causes were censored appropriately.

Time frame: Over a median follow-up time of 44 months post-Dose 1

Number of Subjects Seropositive Against MAGE-A3

A seropositive subject was defined as a subject whose antibody concentration was greater than or equal to (≥) 27.000 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

Time frame: 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

Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

Number of Subjects Seropositive Against Protein D (PD) Antigens

A seropositive subject was defined as a subject whose antibody concentration was greater than or equal to (≥) 100.000 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

Anti-protein D (Anti-PD) Antibody Concentrations

Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

Number of Subjects With Cell-mediated Immunity (CMI) Cluster of Differentiation (CD) 4+ Response

Responders were patients with at least 5x10-⁶ increase in minimal CD4 precursor frequency versus baseline. Any = at least one post treatment time point.

Time frame: 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

Responders were patients with at least 5x10-⁶ increase in minimal CD8 precursor frequency versus baseline. Any = at least one post treatment time point.

Number of Subjects With Cell-mediated Immunity (CMI) CD4+ or CD8+ Response

Responders are patients with at least 5x10-⁶ increase in minimal CD4 or CD8 precursor frequency versus baseline. Any = at least one post treatment time point.

Time frame: 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

Types of recurrence included local, regional and distant metastasis and second primary lung tumours, and comprised: Local recurrence, defined as a tumour within the same lung or at the bronchial stump; Regional recurrence, involving a clinically or radiologically manifest disease in the mediastinum or in supraclavicular nodes; and Distant recurrence, i.e., any tumour arising in the contralateral lung or outside the hemithorax. Gene expression profiling was performed by qRT-PCR in primary tumor samples taken at the time of resection of the tumor, and thus before any study treatment. Gene signature positive (GS+) and negative (GS-) profiles were assessed with a 61-set gene signature (GS) and a classifier which were defined in the Phase II melanoma EORTC 16032-18031 study.

Time frame: Over a median follow up time of 86 months

Number of Subjects With Any and Grade 3 Solicited Local Symptoms

Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.

Time frame: 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

Assessed solicited general symptoms were fatigue, headache, myalgia, nasea, rigors/chills, sweating/diaphoresis, temperature \[defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], vomiting. Any = occurrence of the symptom regardless of intensity grade. Grade 4 Fatigue = Bedridden or disabling. Grade 4 Headache, Myalgia = Disabling. Grade 3 Nausea = No significant intake, requiring i.v. fluids. Grade 3 Rigors/Chills = Not responsive to narcotic medication. Grade 2 Sweating/Diaphoresis = Frequent or drenching. Grade 4 Vomiting = Requiring parenteral nutrition; or physiologic consequences requiring intensive care; haemodynamic collapse. Grade 3 fever = fever higher than (\>) 40.0 °C for more than 24 hours. Related = symptom assessed by the investigator as related to the vaccination.

Time frame: During the 8-day (Days 0-7) post-vaccination period, across doses

Number of Subjects With Any Unsolicited Adverse Events (AEs)

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

Time frame: Within the 31-day (Days 0-30) post-vaccination period

Number of Subjects With Serious Adverse Events (SAEs)

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

Time frame: Throughout the study (Day 0 - Month 86)

Number of Subjects With Normal and Abnormal Urinalysis Parameters

The parameters analysed were Protein, Red Blood Cells (RBC) and White Blood Cells (WBC), with respect to normal laboratory ranges. The subjects were grouped by status at baseline.

Time frame: At Month 6, Month 12, Month 18, Month 24 and Month 30

Number of Subjects With Normal and Abnormal Hematological Parameters

The parameters analysed were Basophils (BAS), Eosinophils (EOS), Haemoglobin (HGB), Lymphocytes (LYM), Monocytes (MON), Neutrophils (NEU), Platelets (PLA), Red Blood Cells (RBC), Sedimentations rate (SED) and White Blood Cells (WBC), with respect to normal laboratory ranges. The subjects were grouped by status at baseline.

Time frame: At Month 6, Month 12, Month 18, Month 24 and Month 30

Number of Subjects With Normal and Abnormal Biochemical Parameters

The parameters analysed were Albumin (ALB), Bicarbonate (BIC), Blood urea nitrogen (BUN), Calcium (CAL), Chloride (CHL), Cholesterol (CHO), Creatinine (CREA), Glucose (GLU), Magnesium (MAG), Phosphate (PHO), Potassium (POT), Sodium (SOD), Total protein (TPROT), Total bilirubin (TBIL), Triglycerides (TRIG) and Uric acid (UAC), with respect to normal laboratory ranges. The subjects were grouped by status at baseline.

Time frame: At Month 6, Month 12, Month 18, Month 24 and Month 30