| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
MET DIAGNOSTIC−POSITIVE NON−SMALL CELL LUNG CANCER
(NSCLC) |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025054 |
| E.1.2 | Term | Lung cancer non-small cell stage IIIB |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025055 |
| E.1.2 | Term | Lung cancer non-small cell stage IV |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025048 |
| E.1.2 | Term | Lung cancer non-small cell recurrent |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 study is to determine whether the combination of onartuzumab + erlotinib is superior (in terms of overall survival) to placebo + erlotinib after standard platinum-based chemotherapy in patients with Met diagnostic−positive NSCLC.
|
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are as follows:
• To evaluate and compare the efficacy in terms of progression free survival (PFS) and objective response rate (ORR) between the two treatment groups
• To evaluate and compare the safety and tolerability of onartuzumab + erlotinib versus placebo + erlotinib in patients with Met diagnostic−positive NSCLC
• To evaluate the impact of onartuzumab on patient-reported outcome (PRO) measures of quality of life
• To evaluate the pharmacokinetics of onartuzumab
• To evaluate serum levels and incidence of anti-therapeutic antibodies (ATAs) against onartuzumab and to explore the potential relationship of the immunogenicity response with pharmacokinetics, safety, and efficacy
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
DNA REPOSITORY SUBSTUDY IN ASSOCIATION WITH MetMAb STUDY OAM4971g
OAM4971g (DNA Substudy), 11 July 2011
Objective:
The primary objective of this study is to perform exploratory analyses to generate hypotheses identifying genes associated with treatment response, toxicity, or disease risk. If such genetic hypotheses are identified, they may be tested in future clinical studies within this therapeutic area |
|
| E.3 | Principal inclusion criteria |
• Signed, written informed consent prior to any study-specific screening procedure Note: All patients will be required to sign an updated informed consent that will provide them with information about the results of the interim analysis in order to continue receiving study treatment after the completed interim analysis.
• Male or female, 18 years of age or older
• ECOG performance status of 0–1
• Histologically or cytologically confirmed incurable Stage IIIB/IV NSCLC tumour
• Met diagnostic-positive status (≥50% of tumour cells with membrane and/or cytoplasmic staining at moderate to high intensity) and results of EGFR-activating mutation testing, as determined by the central laboratory
• Radiographic evidence of disease (measurable disease not mandatory)
• Prior treatment with at least one platinum-based line of treatment for locally advanced, unresectable/inoperable disease or metatstatic disease, and no more than one additional line of chemotherapy treatment
|
|
| E.4 | Principal exclusion criteria |
• More than 30 days of exposure to an investigational or marketed agent that can act by EGFR inhibition, or a known EGFR-related toxicity resulting in dose modifications (such as gefitinib, erlotinib, cetuximab)
• Pleural effusion, pericardial fluid, or ascites requiring drainage every other week or more frequently
• Brain metastasis or spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated central nervous system metastases or spinal cord compression without evidence of clinically stable disease for ≥ 14 days
• History of another malignancy in the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other malignancies with an expected curative outcome
• Life expectancy less than 12 weeks
• Radiographically evident ILD, as evidenced by one or more of the following: interstitial pneumonia, pneumonitis, radiation pneumonitis, organising pneumonia, pulmonary fibrosis, acute respiratory distress syndrome, lung infiltration, or alveolitis, or a history of these conditions
• Granulocyte count < 1,500/mm3, platelet count < 100,000/mm3, or haemoglobin < 9.0 g/dL
• AST (SGOT), ALT (SGPT), alkaline phosphatase (ALP) > 2.5 × upper limit of normal (ULN)
• Total bilirubin > 1.5 × ULN
• Albumin ≤ 2.5 g/dL
• Uncontrolled hypercalcaemia (> 1.5 mmol/L ionized calcium, or corrected serum calcium > ULN), or symptomatic hypercalcaemia requiring continued use of bisphosphonate therapy
• Serum creatinine > 1.5 X ULN
• Significant history of cardiac disease
• Serious active infection at the time of randomisation or other serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment. This includes patients known to be HIV-positive or patients with known active hepatitis B or C
• Any inflammatory changes of the surface of the eye
• Clinically significant gastrointestinal abnormalities, including uncontrolled inflammatory gastrointestinal diseases
• Unable to take oral medication, need for intravenous feeding, prior surgical procedures affecting absorption, or active peptic ulcer disease
• Patients with uncontrolled diabetes mellitus, as evidenced by fasting serum glucose level > 200 mg/dL
• Any major surgery within 2 weeks prior to randomisation
• Pregnant or lactating women, or positive pregnancy test within 48 hours before starting study drug treatment
• Women of childbearing potential (< 1 year amenorrheic) or sexually active males who are not employing adequate contraception (or practicing complete abstinence)
• Inability to understand the local language(s) for which the EORTC QLQ-C30 and QLQ-LC13 questionnaires are available
• Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with study and follow-up procedures |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary analysis: when 364 deaths have occurred
Interim analysis: when 243 deaths have occurred |
|
| E.5.2 | Secondary end point(s) |
• Progression-free survival
• Objective response rate
• Health related quality of life
• Adverse events
• Laboratory results
• Pharmacokinetics
• Incidence of antibodies against MetMAb
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Primary analysis: when 364 deaths have occurred
Interim analysis: when 243 deaths have occurred |
|
| 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 | Yes |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability, QoL, Serum levels and incidence of anti-therapeutic antibodies (ATAs) against onartuzumab |
|
| 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Erlotinib + onartuzumab vs Erlotinib + Placebo |
|
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 59 |
| 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 |
| Belgium |
| Brazil |
| Canada |
| Chile |
| China |
| Croatia |
| France |
| Germany |
| Hong Kong |
| Hungary |
| Ireland |
| Israel |
| Italy |
| Japan |
| Korea, Republic of |
| Malaysia |
| Netherlands |
| Peru |
| Poland |
| Romania |
| Russian Federation |
| Serbia |
| South Africa |
| Spain |
| 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
|
| Patients will be followed for survival until about 67% of OS events in patients with EGFR mutation−positive NSCLC have been recorded in database or until Sponsor decides to discontinue OS fo-up.They receiving onartuzumab or control treatment at the time of the interim analysis will be allowed to continue at the discretion of the treating physician until disease progression,onset of treatment-limiting toxicity,or when the treating physician decides to discontinue treatment,whichever occurs first. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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