Adjuvant therapy in patients with MAGE-A3-positive Non-Small Cell Lung Cancer (NSCLC) and who have had complete surgical resection MedDRA version: 14.1 Level: PT Classification code 10029520 Term: Non-small cell lung cancer stage IIIA System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecif
Conditions
Sponsors
GlaxoSmithKline Biologicals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female patient with completely resected, pathologically proven stage IB, II or IIIA NSCLC according to AJCC Version 6.0. 2.Written informed consent for MAGE-A3 expression screening and the gene expression signature testing on tumor biopsy has been obtained from the patient prior to shipment of the sample for MAGE-A3 expression and the gene expression signature testing (before or just after surgical resection), and written informed consent for the complete study has been obtained prior to the performance of any other protocol-specific procedure. 3.Patient is 18 years of age or older at the time of signature of the first informed consent form. 4.The patient's tumor shows expression of MAGE-A3 gene. Note: Analysis will be performed on formalin-fixed paraffin-embedded tissue samples. 5.The surgical technique for resection of the patient's tumor is anatomical, involving at least a lobectomy or a sleeve lobectomy. 6.The mediastinal lymph node sampling is done according to study protocol guidelines. 7.The patient is free of metastasis, as confirmed by a negative baseline computer tomogram (CT scan) of the chest, upper abdomen and CT scan or MRI of the brain. Other examinations should be performed as clinically indicated. Note that brain CT scans or brain MRI performed no more than 12 weeks prior to first treatment administration do not have to be repeated unless clinically indicated (i.e., new clinical signs or symptoms suggestive of brain metastases). 8.ECOG performance status of 0, 1 or 2 at the time of randomization. 9.Adequate bone-marrow reserve, adequate renal function and adequate hepatic function as assessed by standard laboratory criteria, and defined as: Absolute neutrophil count: > or = 1.0 x 109/L Platelet count: > or = 75 x 109/L Serum creatinine: =65 years) yes F.1.3.1 Number of subjects for this age range 1056
Exclusion criteria
Exclusion criteria: 1.The primary tumor was removed by segmentectomy or wedge resection. 2.The patient shows any evidence of residual tumor after surgery. 3.The patient has received any anti-cancer specific treatment, including radiotherapy, immunotherapy, chemotherapy or neo-adjuvant chemotherapy, except: - For the treatment of previous malignancies as allowed by the protocol (i.e., non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years), - Administration of adjuvant platinum-based chemotherapy for the treatment of the current NSCLC is allowed between surgery and randomization. 4.The patient has previous or concomitant malignancies, except effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years and highly likely to have been cured. 5.History of allergic disease or reactions likely to be exacerbated by any component of the study investigational product. 6.The patient has an autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded. 7.The patient requires concomitant treatment with any immunosuppressive agent, or with systemic corticosteroids prescribed for chronic treatment (more than 7 consecutive days). Note: The use of prednisone, or equivalent, <0.5 mg/kg/day (absolute maximum 40 mg/day), or inhaled corticosteroids or topical steroids is permitted. 8.The patient has received a major organ allograft. 9.The patient is known to be HIV-positive. 10.The patient has an uncontrolled bleeding disorder. 11.The patient has uncontrolled congestive heart failure or hypertension, unstable heart disease (coronary artery disease or myocardial infarction) or uncontrolled arrhythmia at the time of enrolment. 12.The patient needs home oxygenation. 13.The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the trial procedures. 14.The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk. 15.The patient has received any investigational or non-registered medicinal product other than the study medication within the 30 days preceding the first dose of study medication, or plans to receive such a drug during the study period. 16.For female patients: the patient is pregnant or lactating.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Overall survival, defined as interval from randomization to the date of death, irrespective of the cause of death. •Lung cancer specific survival, defined as the interval from randomization to the date of death due to lung cancer. •Disease-free survival at 2, 3, 4 and 5 years. •Disease-free specific survival (only lung cancerrelated events will be taken into account. ;Timepoint(s) of evaluation of this end point: At predefined timepoints | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this Phase III study is to demonstrate the clinical efficacy (in terms of disease-free survival) of recMAGE-A3 + AS15 versus placebo in NSCLC after complete surgical resection. three co-primary objectives are considered: •Objective A: Efficacy in the overall population; •Objective B: Efficacy in the population of patients who did not receive adjuvant chemotherapy (no-CT population). •Objective C: Efficacy in the population of patients presenting the potentially favourable gene signature.;Secondary Objective: •To evaluate and compare recMAGE-A3 + AS15 ASCI versus placebo with respect to efficacy in patients who received adjuvant chemotherapy and in patients who do not present the favourable gene signature. •To evaluate and compare recMAGE-A3 + AS15 ASCI versus placebo with respect to safety and other clinical and biological indicators of safety and efficacy in the overall population, in patients who received adjuvant chemotherapy, in patients who did not receive this chemotherapy, in patients presenting the potentially favourable gene signature and in patients who do not present this signature. •To validate the predictive value of the gene sigature by evaluating the association between treatment outcome (DFS) and gene signature status. •To evaluate and compare the changes in health-related quality of life (utility) in patients treated with recMAGE-A3 + AS15 ASCI compared to those treated with placebo using the EuroQol-5D questionnaire (EQ-5D). ;Primary end point(s): The primary efficacy endpoint will be disease-free survival (DFS). DFS is defined as the interval from the date of randomization to the date of the first objective evidence of recurrence or to the date of death, if before recurrence. All types of recurrence will be included. These include local, regional and distant metastasis and second primary lung tumors, as follows: •Local recurrence, defined as a tumour within the same lung or at the bronchial stump, •Regiona | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czech Republic, Estonia, Finland, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Netherlands, Norway, Poland, Russian Federation, Singapore, Slovenia, Spain, Sweden, Switzerland, Taiwan, Thailand, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Disclosure Advisor
GlaxoSmithKline Biologicals Belgium
Outcome results
None listed