E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Platinum-refractory, locally advanced or metastatic non-small cell lung cancer (NSCLC) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.0 |
E.1.2 | Level | VTb |
E.1.2 | Classification code | 10061873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
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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 compare the progression-free survival (PFS) for SU011248 plus erlotinib versus placebo plus erlotinib in patients with platinum-refractory NSCLC. |
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E.2.2 | Secondary objectives of the trial |
• To compare the objective response rate (ORR) for SU011248 plus erlotinib versus placebo plus erlotinib as treatment for platinum-refractory NSCLC. • To compare measures of duration of tumor control and survival. • To compare the safety and tolerability of SU011248 plus erlotinib versus placebo plus erlotinib. • To evaluate the plasma pharmacokinetics of erlotinib and SU011248 and its active metabolite SU012662 when these drugs are co-administered. • To explore the relationships of cancer biomarkers with cancer- and treatment-related outcomes. • To compare patient reported outcomes (PRO) including health-related quality of life (HRQOL) and lung cancer-related symptoms in patients treated with SU011248 plus erlotinib versus placebo plus erlotinib. |
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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 |
TITLE: RANDOMIZED, DOUBLE-BLIND, PHASE 2 STUDY OF ERLOTINIB WITH OR WITHOUT SU011248 IN THE TREATMENT OF METASTATIC NON-SMALL CELL LUNG CANCER
Version and Date: Final - 2 September 2005
STUDY OBJECTIVES: The primary objective of this additional research component is to allow for the collection, storage, and use of samples to investigate possible associations between genetic variation in relation to response to the combination of erlotinib and SU011248 and in relation to characteristics of Non Small Cell Lung Cancer (NSCLC) and related conditions. Scientific information about these differences among groups of subjects can help researchers to better understand the response of subjects to investigational drugs such as SU011248 and to learn more about conditions such as NSCLC.
The second objective is to collect, store, and use the samples as controls in genetic investigations of the causes, natural history, and other aspects of important diseases and conditions for which Pfizer is researching new or improved drug therapies. |
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E.3 | Principal inclusion criteria |
1. Histologically proven diagnosis of NSCLC. 2. Disease that is locally advanced (Stage IIIB with malignant effusion), metastatic (Stage IV), or recurrent (after treatment for Stage IIIB with malignant effusion or Stage IV NSCLC). 3. Prior treatment with 1 or 2 chemotherapy regimens including a platinum-based regimen for advanced disease (Stage IIIB with malignant effusion or Stage IV). 4. Evidence of unidimensionally measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST). 5. Radiographic evidence of disease progression during or following treatment in the advanced disease setting confirmed by the Principal Investigator prior to enrollment in the study. 6. Formalin-fixed, paraffin-embedded tumor tissue available from patients enrolling into the randomized component of this study. (Paired samples collected at the time of the most recent recurrence and at the initial diagnosis are optimal, though samples collected at any time are acceptable). 7. Male or female, 18 years of age or older. 8. ECOG performance status 0 or 1. 9. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade ≤1 (except alopecia). 10. Adequate organ function as defined by the following criteria: • NCI CTCAE severity ≤ 2 for dyspnea • 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/µL • Platelets ≥100,000/µL • Hemoglobin ≥9.0 g/dL • Serum creatinine ≤1.5 x ULN 11. 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. 12. 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 >2 systemic chemotherapy-based regimens for advanced disease (Stage IIIB with malignant effusion or Stage IV). 2. Prior treatment with any receptor tyrosine kinase inhibitors, VEGF inhibitors, or other angiogenic inhibitors (including but not limited to SU011248, erlotinib, gefitinib, or thalidomide). Note: Patients previously treated with bevacizumab or an IGFR inhibitor will be considered eligible for study entry. 3. Major surgery, radiation therapy, or systemic therapy within 4 weeks of starting the study treatment. 4. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue. 5. Prior radiation therapy to >25% of the bone marrow. 6. 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. 7. History of or known brain metastases, spinal cord compression, carcinomatous meningitis, or new evidence of brain or leptomenengeal disease on screening CT or MRI scan. 8. Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma that has been adequately treated. 9. 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. 10. 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. 11. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy). 12. Ongoing treatment with therapeutic doses of warfarin (however low dose warfarin up to 2 mg daily for deep vein thrombosis prophylaxis is allowed during the Phase 2 component of this study but not during the lead-in portion). 13. Known human immunodeficiency virus (HIV) infection. 14. Current treatment on another therapeutic clinical trial. 15. Pregnancy or breastfeeding. 16. 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-Free Survival (PFS) |
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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 | Yes |
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 | Yes |
E.6.12 | Pharmacoeconomic | No |
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) | 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 | 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 | 12 |
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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Patients should continue to receive treatment as assigned at randomization until RECIST-defined disease progression or for up to 18 cycles. At the time of progression or after 18 cycles on study patients will be unblinded to treatment assignment and all patients offered continued access to SU011248 through participation on a separate protocol at the discretion of the investigator. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |