E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic non small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. |
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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 | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
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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 demonstrate that the combination of sunitinib plus erlotinib is superior to erlotinib plus placebo in prolonging the overall survival (OS) for advanced/metastatic NSCLC patients who have received 1 to 2 prior chemotherapy regimens. |
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E.2.2 | Secondary objectives of the trial |
To compare measures of antitumor response [progression-free survival (PFS); overall response rate (ORR)] and duration of tumor control [duration of response (DR)] between both treatment arms.
To compare the safety and tolerability of erlotinib plus sunitinib versus erlotinib plus placebo in this patient population.
To assess patient reported outcomes.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically proven diagnosis of NSCLC with evidence of disease that is recurrent (after treatment for Stage IIIB with malignant effusion or Stage IV NSCLC) and for which erlotinib treatment is clinically indicated. 2. Prior treatment with 1 or 2 chemotherapy regimens (including a platinum based regimen) for advanced disease (Stage IIIB with malignant effusion or Stage IV NSCLC).] 3. Disease progression during or after first-line chemotherapy 4. Measurable or nonmeasurable disease. 5. Male or female, 18 years of age or older. 6. ECOG performance status 0 or 1. 7. Resolution of all acute toxic effects of prior therapy or surgical procedures to Grade <=1 (except alopecia). 8. Adequate organ function as defined by the following criteria: • Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) <=2.5 x upper limit of normal (ULN), or AST and ALT <=5 x ULN if liver function abnormalities are due to underlying malignancy • Total serum bilirubin <=1.5 x ULN • Serum albumin >=3.0 g/dL • Absolute neutrophil count (ANC) >=1500/mL • Platelets >=100,000/mL • Hemoglobin >=9.0 g/dL • Serum creatinine <=1.5 x ULN 9. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment. 10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. |
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E.4 | Principal exclusion criteria |
1. Prior treatment with any receptor tyrosine kinase inhibitors (including but not limited to sunitinib, erlotinib, and gefitinib), VEGF inhibitors (with the exception of bevacizumab), or other angiogenesis inhibitors (including but not limited to thalidomide). 2. Treatment with sunitinib and/or erlotinib if it is contraindicated according to the local prescribing information. 3. Major surgery within 4 weeks of study treatment. At least 7 days should elapse since minor surgical procedure including placement of an access device or fine needle aspiration. 4. Tumor (any histology) that involves a major blood vessel (eg, no aortic involvement). 5. Major radiation therapy within 4 weeks of study treatment except palliative radiotherapy to non target metastatic lesions. 6. Systemic anticancer therapy within 4 weeks of starting the study treatment. 7. Prior treatment with a platinum based regimen as adjuvant therapy following resection for early stage NSCLC. 8. Prior high dose chemotherapy requiring hematopoietic stem cell rescue. 9. Prior radiation therapy to >25% of the bone marrow. 10. Evidence of hemoptysis <4 weeks of starting study treatment. Patients with blood tinged or blood streaked sputum will be permitted on study if the hemoptysis amounts to less than 5 mL of blood per episode and less than 10 mL of blood per 24 hour period in the best estimate of the Investigator. 11. Presence or history of brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. 12. Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell carcinoma or squamous cell skin cancer, or carcinoma in situ of the cervix uteri. 13. Any of the following within the 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolism. 14. Ongoing cardiac dysrhythmias of NCI CTCAE grade >=2, atrial fibrillation of any grade, or QTc interval >450 msec for males or >470 msec for females. 15. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy). 16. Severe dry eye syndrome, Sjogren's syndrome, severe exposure keratopathy, bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis, or clinically significant gastrointestinal abnormalities including uncontrolled inflammatory disease (eg, Crohn's or ulcerative colitis). 17. Known human immunodeficiency virus infection. 18. Current treatment on another clinical trial. 19. Pregnancy or breastfeeding. Female patients, who are pregnant or nursing, or men and women of reproductive potential who are unwilling or unable to use adequate contraception to prevent pregnancy during the program. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to study entry. 20. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the Investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the Investigator, would make the patient inappropriate for entry into this study. 21. Current treatment with therapeutic doses of coumarin derivative anticoagulants, such as warfarin (however, low dose up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). If currently receiving prophylaxis, PT or INR must be <1.5 times the ULN. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | 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 |
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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 | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 150 |
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 | 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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At the end of the study or at withdrawal, scheduled visits should be performed. For further details please refer to section 6 of the protocol. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 16 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 20 |