E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adjuvant therapy in patients with MAGE-A3-positive Non-Small Cell Lung Cancer (NSCLC) and who have had complete surgical resection |
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E.1.1.1 | Medical condition in easily understood language |
Non-Small Cell Lung Cancer after surgery |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029520 |
E.1.2 | Term | Non-small cell lung cancer stage IIIA |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029518 |
E.1.2 | Term | Non-small cell lung cancer stage II |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029517 |
E.1.2 | Term | Non-small cell lung cancer stage I |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
•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 potentially favourable gene signature. •To evaluate and compare recMAGE-A3 + AS15 ASCI versus placebo with respect to safety and other clinical and biological indicators of 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 expression signature and in patients who do not present this signature. •To validate the predictive value of the gene signature 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).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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: < or = 1.5 times the Upper Limit of Normal (ULN) < or = 3.0 times the ULN if due to platinum adjuvant chemotherapy Total bilirubin: < or = 1.5 times the ULN Alanine transaminase (ALAT): < or = 2.5 times the ULN 10.If the patient is female, she must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post menopausal, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to administration of study treatment, have a negative pregnancy test and continue such precautions during all study treatment period and for 2 months after completion of the injection series. 11.In the view of the investigator, the patient can and will comply with the requirements of the protocol.
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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, •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. In addition, all deaths occurring without prior documentation of tumor recurrence will be considered as an event (and will not be censored in the statistical analysis) as this approach is less prone to introducing bias. If no event (recurrence or death) occurs by the time of the analysis, then the time to event will be censored at the date of the last assessment of the patient in question. Any new primary cancer will not be considered as recurrence and should be reported as SAE. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 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 cancer related events will be taken into account) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 230 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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 |
Netherlands |
Norway |
Poland |
Russian Federation |
Singapore |
Spain |
Sweden |
Switzerland |
Taiwan |
Thailand |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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For each patient, the study treatment phase ends at Visit 14. It will then be followed by follow-up visits up to 5 years after the first study treatment administration. The end of trial is defined as the last follow-up visit of the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 9 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |