E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-small cell lung cancer (NSCLC) - patients with inoperable stage IIIb or IV NSCLC have a very poor prognosis, with overall survival of 4-8 months. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Information not present in EudraCT |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the activity of EPO906 administered once every 3 weeks to patients with advanced NSCLC |
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E.2.2 | Secondary objectives of the trial |
1. determine the time to progression (TTP), duration of overall response (OR) and stable disease, time to OR and overall survival of patients receiving EPO906 (q3w) 2. evaluate the activity of EPO906 (q3W) to NSCLC metastatic to brain patients, 3. assess the safety and tolerability of EPO906 (q3W) 4. assess the incidence and the severity of diarrhea in patients receiving EPO906 with intensive management of CID. 5. evaluate PK of EPO906 at the MTD level after a single dose and multiple doses 6. investigate tumor-specific mutations and compare gene expression changes in tumor cells with blood cells and plasma for biomarker development. 7. perform pharmacogenetic analyses with blood samples from patients who agree to participate in this part of the trial. 8. assess patient’s symptoms and quality of life (QoL). 9. capture the level of medical resource utilization during the treatment period. 10. assess patients’ expectations of treatment efficacy and side effects |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• Patients with histologic or cytologic confirmation of unresectable locally advanced or metastatic NSCLC (stage IIIB with pleural effusion only / stage IV) documented before first line therapy. • Prior treatment with a platinum-containing regimen • At least 18 years old • Performance status of 0-1 on the WHO scale. • Life expectancy equal or greater than 3 months. • NSCLC patients should have at least one measurable lesion as defined by modified RECIST criteria. If the patient has had previous radiation to the marker lesion(s), the lesion must have demonstrated progression since the radiation. • NSCLC patients with controlled brain metastases are eligible to be enrolled in the brain metastases cohort at the MTD. “Controlled brain metastases” patients are defined as patients who are neurologically stable, i.e. have not experienced an increase in dose of steroidal or anticonvulsive therapy for at least 14 days prior to study entry. • Patients with brain metastases must be verified to have metastases secondary to NSCLC based on histology of primary and by temporal sequence of events (note: these patients are eligible even if lung disease is quiescent). • Patients with brain metastases must show evidence of residual disease or progression of disease since prior radiological or surgical therapy. • Patients with brain metastases should have at least one bidimensionally measurable intracranial lesion of minimum diameter 2 cm. Multifocal disease is permitted, but the eligibility of BM patients presenting with more than 6 intracranial lesions should be discussed with Novartis prior to enrolling the patient. • Patients with adequate hematologic parameters and blood chemistry values as defined per protocol • Female patients must have a negative serum pregnancy test at screening. (Not applicable to patients with bilateral oophorectomy and/or hysterectomy or to those patients who are postmenopausal). • All patients of reproductive potential must agree to use an effective method of contraception during the study and three months following termination of treatment. • All patients must use a barrier method for contraception for sexual intercourse or avoid this for the first 5 days after EPO906 infusion |
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E.4 | Principal exclusion criteria |
• Patients who have received more than one prior chemotherapy regimen or any other systemic antineoplastic treatment including immunotherapy. • Patients who have received any investigational compound within the past 28 days or who are planning to receive other investigational drugs while participating in the study. • Patients with brain metastases who have received any prior chemotherapy regimen or any other systemic antineoplastic treatment for brain metastases. • Patients with brain metastases who have experienced a dose increase of 25% or more above previous dose, in concomitant steroidal or anticonvulsive therapy within 14 days prior to study entry. • Patients with brain metastases receiving steroidal or anticonvulsive therapy for whom a dose increase has been required within 14 days prior to start of study drug. • Patients with brain metastases who have leptomeningeal disease. • Patients with brain metastases who have extracranial metastases in more than two organs. • Patients with any peripheral polyneuropathy > Grade 1. • Patients with unresolved diarrhea > Grade 1. • Patients receiving hematopoietic growth factors except erythropoietin • Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or unstable cardiac or coronary artery disease. • Patients taking Coumadin® or other agents containing warfarin, with the exception of low dose Coumadin® (1 mg or less daily) administered prophylactically for maintenance of in-dwelling lines or ports. • Patients who have not recovered fully from surgery for any cause, including brain metastases patients who have had a biopsy or surgical resection of the brain tumor within 2 weeks prior to starting study drug or who are not fully recovered from any prior biopsy or surgical resection. • Patients who have received radiation therapy or chemotherapy within the last four weeks. Palliative radiotherapy of metastasis in extremities is allowed but such lesions cannot be used as tumor markers. • Patients with the presence of active or suspected acute or chronic uncontrolled infection, including abscess or fistulae. • Patients known to be HIV positive. • History of another malignancy within 3 years prior to study entry, except curatively treated non-melanotic skin cancer or cervical cancer in situ. • For patients enrolling in the brain metastases cohort, any of the following preclusions to MRI imaging: Cardiac pacemaker Ferromagnetic metal implants other than those approved as safe for use in MRI scanners Claustrophobia Obesity (exceeding the limits of scanning equipment) • Pregnant or lactating females. • A history of noncompliance to medical regimens or inability or unwillingness to return for all scheduled visits.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point for the second stage is to determine the activity of EPO906 administered once every 3 weeks to patients with advanced NSCLC, as defined by overall response rate (CR + PR) according to modified RECIST using Simon’s two-stage design |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 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.8.6 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 | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
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 | 2 |