| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Non-small cell lung cancer (NSCLC) subjects with unresectable stage III disease |
|
| E.1.1.1 | Medical condition in easily understood language |
| Non-small cell lung cancer (NSCLC) |
|
| 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 | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10029519 |
| E.1.2 | Term | Non-small cell lung cancer stage III |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
Primary objective:
· To compare survival duration of all randomized subjects by treatment arm. |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives of this trial are to compare all randomized subjects by treatment arm for:
· Time to symptom progression (TTSP) as measured by the Lung Cancer Symptom Scale (LCSS).
· Time to progression (TTP) as determined by the investigator.
· One-, two- and three-year survival.
· Safety. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Both inpatient and outpatient, male and female subjects are eligible for randomization.
· Subject has given written informed consent before any study-related activities are carried out.
· Histologically or cytologically documented unresectable stage III NSCLC. All histological subtypes are acceptable, including bronchioalveolar carcinomas. Cancer stage must be confirmed and documented by computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET) scan.
· Documented stable disease or objective response, according to RECIST, after primary chemo-radiotherapy (either sequential or concomitant) for unresectable stage III disease, within 4 weeks (28 days) prior to randomization*.
· Receipt of concomitant or sequential chemo-radiotherapy, consisting of a minimum of two cycles of platinum-based chemotherapy and a minimum radiation dose of ≥ 50 Gy. Subjects must have completed the primary thoracic chemo-radiotherapy at least four weeks (28 days) and no later than 12 weeks (84 days) prior to randomization. Subjects who received prophylactic brain irradiation as part of primary chemo-radiotherapy are eligible.
· Geographically accessible for ongoing follow-up, and committed to comply with the designated visits.
· An ECOG performance status of 0-1.
· A platelet count ≥ 140 x 109/L; WBC ≥ 2.5 x 109/L and hemoglobin ≥ 90 g/L.
· ≥18 years of age.
* If imaging after primary chemo-radiotherapy was earlier than 4 weeks prior to randomization, it must be repeated within 4 weeks prior to randomization, and the results of the second restaging after end of primary chemo-radiotherapy must be compared with the first restaging after end of primary chemo-radiotherapy. Subjects that show progression between these two assessments are not eligible for this trial. |
|
| E.4 | Principal exclusion criteria |
Pre-Therapies:
· Undergone lung cancer specific therapy (including surgery) other than primary chemo-radiotherapy.
· Receipt of immunotherapy (e.g. interferons, tumor necrosis factor [TNF], interleukins, or biological response modifiers [granulocyte macrophage colony stimulating factor {GM-CSF}, granulocyte colony stimulating factor {G-CSF}, macrophage-colony stimulating factor {M-CSF}], monoclonal antibodies) within 4 weeks (28 days) prior to randomization. Note: Subjects who have received monoclonal antibodies for imaging are acceptable.
· Receipt of investigational systemic drugs (including off-label use of approved products) within 4 weeks (28 days) prior to randomization.
Disease Status:
· Metastatic disease.
· Malignant pleural effusion at initial diagnosis and/or at study entry.
· Past or current history of neoplasm other than lung carcinoma, except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix or other cancer curatively treated and with no evidence of disease for at least 5 years.
· Autoimmune disease
· A recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have hereditary or congenital immunodeficiencies.
· Any preexisting medical condition requiring chronic steroid or immunosuppressive therapy (steroids for the treatment of radiation pneumonitis are allowed).
· Known Hepatitis B and/or C.
Physiological Functions:
· Clinically significant hepatic dysfunction (i.e. Alanine aminotransferase [ALT] > 2.5 times normal upper limit [ULN]; or Aspartate aminotransferase [AST] > 2.5 times ULN; or bilirubin ≥ 1.5 x ULN).
· Clinically significant renal dysfunction (i.e. serum creatinine ≥ 1.5 x ULN).
· Clinically significant cardiac disease, e.g. New York Heart Association (NYHA) classes III-IV; uncontrolled angina, uncontrolled arrhythmia or uncontrolled hypertension, myocardial infarction in the previous 6 months as confirmed by an electrocardiogram (ECG).
· Splenectomy.
· Infectious process that in the opinion of the investigator could compromise the subject’s ability to mount an immune response.
Standard Safety:
· Pregnant or breast-feeding women, women of childbearing potential, unless using effective contraception as determined by the investigator. Subjects whom the investigator considers may be at risk of pregnancy will have a pregnancy test performed per institutional standard.
· Known drug abuse/alcohol abuse.
· Participation in another clinical study within the past 28 days.
· Requires concurrent treatment with a non-permitted drug.
· Known hypersensitivity to any of the study treatment ingredients.
· Legal incapacity or limited legal capacity.
· Any other reason that, in the opinion of the investigator precludes the subject from participating in the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary variable of this study is the survival duration. Survival will be measured as the number of months between the date of randomization and the date of death. Due to the clinical hold, survival will be analysed in the intention-to-treat (ITT) population (primary analysis) and in the per protocol (PP) population but excluding all subjects randomized during the 6 months (=26 weeks) prior to the clinical hold in both analysis populations. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Interim analysis at 353 and 529 events (deaths); final analysis at 705 events (deaths). |
|
| E.5.2 | Secondary end point(s) |
- Time To Symptom Progression (TTSP), as measured by the Lung Cancer Symptom Scale (LCSS)
- Time To Progression (TTP), as measured by the investigator.
- One-, two- and three-tear survival / Analysed at 1, 2, and 3 years post treatment onset.
- Safety / Assessed throughout, from first patient in until last patient out. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Time To Symptom Progression (TTSP), as measured by the Lung Cancer Symptom Scale (LCSS) / Same timepoint as primary endpoint.
- Time To Progression (TTP), as measured by the investigator / Same timepoint as primary endpoint.
- One-, two- and three-tear survival / Analysed at 1, 2, and 3 years post treatment onset.
- Safety / Assessed throughout, from first patient in until last patient out. |
|
| 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 | Yes |
| E.6.13 | Others | No |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 136 |
| 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 |
| Austria |
| Belgium |
| Brazil |
| Canada |
| China |
| Czech Republic |
| Denmark |
| France |
| Germany |
| Greece |
| Hungary |
| India |
| Ireland |
| Israel |
| Italy |
| Korea, Republic of |
| Mexico |
| Netherlands |
| Poland |
| Portugal |
| Romania |
| Russian Federation |
| Singapore |
| Slovakia |
| Spain |
| Sweden |
| Switzerland |
| Taiwan |
| United Kingdom |
| United States |
|
| 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
|
| Provided in the protocol, section 7.7.9. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 8 |
| 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 | 8 |
| 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 |
Print
