E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-small cell lung cancer |
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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 | 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 |
Phase I: To determine the safety and tolerability of erlotinib in combination with MK-0646 in patients with recurrent NSCLC. Phase II: To evaluate the effect of the combination of erlotinib and MK-0646 on PFS in patients with recurrent NSCLC.
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E.2.2 | Secondary objectives of the trial |
Radiological: To quantify response rate (RR) by response criteria in solid tumors (RECIST) criteria.
Clinical: To determine overall survival (OS).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient has histologically or cytologically documented, unresectable, locally advanced or metastatic Stage IIIB/IV NSCLC that has relapsed after chemotherapy/chemoradiotherapy. 2. Patient has a pre-study, diagnostic formalin fixed paraffin-embedded tumor tissue sample available for correlative studies. - Sample is OPTIONAL in the Phase I portion of the study. - Sample is REQUIRED in the Phase II portion of the study. 3. Patient has measurable disease based on RECIST criteria. 4. Patient has had at least one systemic chemotherapy regimen for recurrent or metastatic disease. 5. Patient is male or female, and 18 years of age on the day of signing informed consent. 6. Patient has a performance status 0-2 on the ECOG Performance Scale. 7. Patient must have adequate organ function as indicated by the following laboratory values: - ANC greater than or equal to 1,500/μl; Platelet greater than or equal to 100,000/ μl; Hemoglobin greater than or equal to 9 g/dL; Creatinine <1.5mg/ml; T.bilirubin ≤ ULN, AST/ALT ≤ 1.5x ULN, etc. 8. Female patient of childbearing potential has a negative serum/urine pregnancy test at baseline, 9. Male and female patients, as well as their partners, must agree to use adequate contraception during therapy with MK-0646 alone or in combination with erlotinib. Note that simultaneous use of two reliable forms of contraception is recommended for the entire study period and ending 28±2 days after the last dose of study drug. 10. Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent. |
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E.4 | Principal exclusion criteria |
1. Patient who has had chemotherapy or therapeutic radiotherapy within 2 weeks, or biological therapy such as bevacizumab (Avastin ) within 4 weeks, prior to entering the study or who has not recovered from adverse events due to agents administered more than 4 weeks earlier to at least grade 1 or baseline. 2. Patient who has received prior EGFR TKI inhibitor/anti-EGFR mAb therapy or prior IGF-1R - TKI inhibitor/anti-IGF-1R mAb therapy. 3. Patient who has received more than 2 prior systemic chemotherapy regimens for recurrent or metastatic disease. 4. Patient who has not completed radiotherapy with complete resolution of toxicities at least 2 weeks prior to beginning this study. 5. Patient is currently participating or has participated in a study with an investigational compound or device within 30 days (or 5 half-lives of the investigational compound) of initial dosing with study drug. 6. Patients with active central nervous system (CNS) metastases and/or carcinomatous meningitis are excluded. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 3 months prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids or on a stable dose of steroids. 7. Patient with a primary central nervous system tumor. 8. Patient has known hypersensitivity to the components of study drug or its analogs. 9. Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate. 10. Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 11. Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse. 12. Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study. 13. Patient is known to be Human Immunodeficiency Virus (HIV)-positive. 14. Patient has active Hepatitis A, B or C. 15. Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible. 16. Patient with a history of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localizedprostate carcinoma with PSA <1.0; or who has undergone potentially curative therapy with no evidence of that disease for five years, or who is deemed at low risk for recurrence by his/her treating physician. 17. Patient is concurrently using growth hormone (GH), or growth hormone inhibitors. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The difference in progression-free survival (PFS) between treatment groups. |
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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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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 | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
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 | 3 |