E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cancer de pulmón de células no microcíticas.
To investigate in a randomized fashion if the addition of targeted IGF-1R blockade with R1507 has additional clinical benefit when combined with erlotinib in patients with advanced NSCLC who have failed at least one, but no more than two standard chemotherapy regimens. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
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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 |
To define the proportion of patients with PFS at 12 weeks with the combination of R1507 and erlotinib or a corresponding placebo and erlotinib in patients with advanced Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC) who have failed at least one standard chemotherapy regimen. |
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E.2.2 | Secondary objectives of the trial |
- Define the effect of adding R1507 to erlotinib on progression-free survival, overall survival, objective response rate, time to response, time to progressive disease and duration of response. - Define population PK of R1507 in combination with erlotinib. - Evaluate the safety profile of the combination of R1507 and erlotinib. - Explore the changes in pharmacodynamic markers in responders and non-responders. - Explore candidate biomarkers related to drug mechanism of action. - To explore two doses and schedules of R1507 combined with erlotinib in this setting. |
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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 |
"Proyecto de investigación del banco de muestras de Roche en asociación con el protocolo NO21160: Estudio aleatorizado, doble ciego para determinar el efecto de dos pautas posológicas de R1507 o placebo, ambos en combinación con erlotinib (Tarceva®), sobre la supervivencia libre de progresión en pacientes con cáncer de pulmón no microcítico avanzado que haya progresado de la enfermedad tras haber recibido primera o segunda línea de quimioterapia". Versión A del 25-4-08. Objetivo: Obtener una sola muestra de sangre de los pacientes incluidos que den su consentimiento, en asociación al estudio NO21160, para permitir futuros análisis farmacogenéticos y genéticos |
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E.3 | Principal inclusion criteria |
1. Male and female patients, age ?18 years 2. Able to comply with the protocol 3. Patients must be able to take oral medication 4. Histologically documented inoperable, locally advanced or metastatic (stage IIIB and stage IV) NSCLC. (NOTE: Sputum cytology alone is not acceptable). Tumors with mixed histology should be categorized according to the predominant cell type 5. Prior Treatment: Failed at least one, but no more than two standard chemotherapy regimens 6. Patients who have received maintenance chemotherapy between initial course of therapy (first line) and study entry may enter on the study provided they have not been treated with an agent that targets EGFR or IGF-1R 7. Formalin fixed paraffin embedded tumor tissue samples from initial or subsequent diagnosis representative of the disease must be available for shipment to Roche prior to randomization 8. Measurable disease according to RECIST 9. ECOG performance status 0-2 10. Life expectancy > 12 weeks 11. Adequate hematological function : ANC ?1.5 x 10 exp9/L; platelets ?100 x 10 exp9/L, Hb ?9 g/dL 12. INR ?1.5 and PTT ?1.5 x ULN unless receiving anticoagulant therapy 13. Adequate liver function: Serum bilirubin ?1.5 x ULN; transaminases ?2.5 x ULN (in case of liver metastases <5 x ULN) 14. Adequate renal function: Serum creatinine ? 1.5 X ULN 15. Serum calcium ? 1.1 X ULN 16. HbA1c ? 7% 17. Negative pregnancy test within 7 days of starting study treatment in pre-menopausal women and women < 2 years after the onset of menopause 18. Signed informed consent |
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E.4 | Principal exclusion criteria |
1. Patients must have had a head CT/MRI to evaluate for CNS metastasis within 28 days prior to enrollment. Patients with active CNS lesions are excluded. Patients with radiographically stable, asymptomatic previously irradiated lesions are eligible provided patients is ? 4 weeks beyond completing cranial irradiation and ? 3 weeks off corticosteroid therapy 2. Prior treatment with an investigational or commercial agent that acts via IGF-1R inhibition 3. Prior treatment with an agent that acts via EGFR targeting 4. Administration of any anti-cancer therapies other than those administered in this study during protocol treatment 5. Administration of high doses of systemic corticosteroids. High dose is considered as > 20 mg of dexamethasone a day (or equivalent) for > 7 consecutive days. Dexamethasone may induce CYP3A4 activity. CYP3A4 inhibitors and inducers may influence the plasma level of erlotinib 6. Prior irradiation: 1) Radiotherapy given within the last 4 weeks prior to first dose of study treatment. 2) Palliative radiotherapy for bone lesions outside the thoracic region within 2 weeks prior to the first dose of study treatment 7. Prior Surgery: Surgery (including open biopsy) or significant traumatic injury within the last 2 weeks prior to first dose of study treatment or anticipation of the need for major surgery during study treatment 8. Patients must have recovered from any toxic effects of previously administered therapies and must be randomly assigned to study treatment at least 21 days after chemotherapy (14 days after treatment with vinca alkaloids or gemcitabine) 9. Lactating women 10. Fertile men or women of childbearing potential not using effective methods to prevent pregnancy 11. Other active cancer requiring treatment 12. Known hypersensitivity to any of the study drugs or their excipients 13. Any disease (including psychotic disorders, drug abuse, active infection, uncontrolled hypertension, clinically significant cardiovascular disease for example CVA (? 6 months before randomization), myocardial infarction (? 6 months before randomization), unstable angina, NYHA ? grade 2 CHF, arrhythmia requiring medication, hepatic, renal or metabolic disease (including uncontrolled diabetes mellitus), metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related complications 14. History of allogeneic bone marrow transplantation or organ transplantation 15. Any known significant ophthalmologic abnormalities of the surface of the eye (the use of contact lenses is not recommended) 16. No dysphagia or active gastrointestinal disease or disorder that alters gastrointestinal motility or absorption; no lack of integrity of the gastrointestinal tract (e.g. as significant surgical resection of the stomach or small bowel). Patients unable to swallow intact tablets must be able to swallow tablets dissolved in water 17. Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to starting study treatment |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival at 12 weeks. PFS is defined as the time from start of treatment to first date of documented disease progression or death. This is a dichotomous endpoint, with patients categorized as alive and progression-free at 12 weeks or in progression or dead by 12 weeks. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Progression-free survival |
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.3 |
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 | 50 |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
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 |