E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Small Cell Lung Cancer (phase 3b/4) |
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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 |
Evaluate progression-free survival (PFS) among all eligible patients (ITT population) treated with erlotinib plus ARQ 197 compared to erlotinib plus placebo |
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E.2.2 | Secondary objectives of the trial |
The below mentioned secondary objectives evaluation will be done for all valuable patients and additionally for patients subpopulations characterized by presence or absence k-ras mutations, EGFR associated tumors and c-Met overexpressions at the different combinations. All patients subpopulations will be compared for data regarding patients treated with ARQ 197 + erlotinib compared with patient treated placebo + erlotinib. - progression free survival (PFS) for IIT and subpopulations - overall survival (OS) for IIT and subpopulations - objective response rate (ORR) for IIT and subpopulations - objective response rate (ORR) for IIT patients treated with erlotinib plus placebo following the event of progression on-study and subsequent unblinded cross-over to receive open-label erlotinib plus ARQ 197. - further characterize the safety of ARQ 197 in combination with erlotinib. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Each patient must meet the following criteria to be enrolled in this study: 1. Provide signed and dated informed consent prior to study-specific screening procedures 2. ≥ 18 years old 3. Histologically or cytologically confirmed inoperable locally advanced or metastatic (stage IIIB/IV) NSCLC 4. ≥ one prior chemotherapy regimen (including adjuvant chemotherapy)(not to have included erlotinib or other EGFR inhibiting agent) 5. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (see Appendix 2) 7. Male or female patients of child-producing potential must agree to use double barrier contraception, oral contraceptives or avoidance of pregnancy measures during the study and for 90 days after the last day of treatment 8. Females of childbearing potential must have a negative serum pregnancy test 9. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN) 10. Total bilirubin ≤ 1.5 × ULN 11. Serum creatinine ≤ 1.5 × ULN 12. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L 13. Platelets ≥ 100 x 109/L 14. Confirmed availability of archival pathology samples (10 unstained paraffinembedded slides) or tissue block suitable for subsequent analysis of K-ras, EGFR, and c-Met |
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will be excluded from the study: 1. Previous receipt of erlotinib or other EGFR inhibiting therapy 2. Receipt of any anti-tumor treatment for NSCLC within 4 weeks (2 weeks for radiotherapy) prior to the start of designated treatment 3. Documented major surgical procedure within 4 weeks prior to randomization. 4. Symptomatic central nervous system metastases either considered in the opinion of investigator to be clinically unstable or which require steroids, anti-epileptics, or other symptom-relieving medications 5. Pregnant, breast-feeding, or refusing double barrier contraception, oral contraceptives or avoidance of pregnancy measures 6. Significant gastrointestinal disorder that, in opinion of Investigator, could interfere with the absorption of ARQ 197 and/or erlotinib (e.g. Crohn’s disease, small or large bowel resection, malabsorbtion syndrome) 7. Unable or unwilling to swallow the complete dose of erlotinib or ARQ 197 8. Any known contraindication to treatment with ARQ 197 or erlotinib 9. Any known hypersensitivity to any of component of ARQ 197 or erlotinib 10. Other malignancy within 5 years of randomization, with the exception of adequately treated intraepithelial carcinoma of the cervix uteri, prostate carcinoma with a PSA value < 0.2 ng/ml or basal or squamous cell carcinoma of the skin 11. Previously diagnosed grade 3 or 4 (CTCAE) bradycardia or other heart arrhythmia 12. Any other significant co-mormid condition that, in opinion of the Investigator, would impair study participation or cooperation 13. Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression of the disease |
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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 | 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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
after EOT patients will be unblinded and offered 2 options of treatment (see Addendum, section 2) |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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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After end of treatment subjects will be unblinded, and depending on the arm they will be offered 2 options of treatment, before the ARQ 197-299 (extension to ARQ 197/209) is approved. Subjects who choose to remain on erlotinib monotherapy will be removed following RECIST progression per CT or MRI evaluation using RECIST criteria 1.0. All subjects regardless of treatment arm will follow the same study visit schedule (see Section 3 of Addendum) |
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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 |