E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously Untreated Extensive Stage Small Cell Lung Cancer (SCLC) |
|
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 | 10041067 |
E.1.2 | Term | Small cell lung cancer |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part 1: To identify a dose of AMG 479 in combination with etoposide plus carboplatin and/or etoposide plus cisplatin and of AMG 102 in combination with etoposide plus carboplatin and/or etoposide plus cisplatin that can be administered safely and is tolerated as determined by the incidence of dose-limiting toxicity (DLT) Part 2: To estimate the relative treatment effect of AMG 479 (at the dose selected in Part 1), and of AMG 102 (at the dose selected in Part 1), and of placebo plus platinum-based chemotherapy (etoposide plus carboplatin and/or etoposide plus cisplatin, as determined in part 1) compared with placebo plus chemotherapy, as measured by the respective hazard ratios (HR) for overall survival (OS). |
|
E.2.2 | Secondary objectives of the trial |
Part 1: To evaluate safety as assessed by the incidence of adverse events and laboratory abnormalities not defined as DLT To evaluate safety as assessed by the incidence of anti-AMG 479 antibody formation and anti-AMG 102 antibody formation To evaluate pharmacokinetics (PK) as assessed by the maximum observed serum concentration (Cmax) and the minimum observed serum concentration (Cmin) for AMG 479 and for AMG 102 Part 2: To evaluate clinical benefit as assessed by the objective response rate (ORR) as measured by modified Response Evaluation Criteria in Solid Tumors (RECIST), duration of response (DOR), time to progression (TTP), progression-free survival (PFS), median OS (mOS), and OS rates at 10, 12, 24 and 36 months To evaluate safety as assessed by the incidence of adverse events and laboratory abnormalities For remaining secondary objectives and for exploratory objectives please see the protocol |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Disease related • Histologically or cytologically confirmed SCLC • Extensive disease, defined by at least one of the following criteria: - No limited disease (ie, no disease confined to the ipsilateral hemithorax, which can be safely encompassed within a tolerable radiation field) - Extrathoracic metastases - Malignant pericardial or pleural effusion - Contralateral hilar adenopathy • Measurable or non-measurable disease, as defined by modified RECIST (see Appendix E) • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (see Appendix I) • Life expectancy (with therapy) ≥ 3 months Demographic • Woman or man ≥ 18 years old Ethical • Before any study-specific procedure, the appropriate written informed consent must be obtained (see Section 12.1) Laboratory • Hematological function (within 3 days prior to enrollment), as follows: - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L - Platelet count ≥ 100 x 109/L - Hemoglobin ≥ 9 g/dL • Partial thromboplastin time (PTT) ≤ 1.2 x upper limit of normal (ULN) and international normalized ratio (INR) ≤ 1.5 • Renal function, as follows: - Creatinine (Cr) clearance (CrCl) ≥ 60 mL/minute (min); calculated by Cockcroft-Gault formula (see Appendix D) as follows: Male CrCl = (140 - age) x (weight in Kg) / (serum Cr x 72) Female CrCl = (140 - age) x (weight in Kg) x 0.85 / (serum Cr x 72) • Hepatic function, as follows: - Aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN if attributable to liver metastases) - Alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if attributable to liver metastases) - Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 x ULN if attributable to bone and/or liver metastases) - Bilirubin ≤ 1.5 x ULN (≤ 3 x ULN for subjects with UGT1A1 promoter polymorphism ie, Gilbert syndrome, confirmed by genotyping or Invader UGT1A1 molecular assay prior to enrollment) • Adequate glycemic function, for subjects with known diabetes (Type 1 or 2), as follows: - Must be controlled with a glycosylated hemoglobin (HgbA1c) of ≤ 8.0% - Documented fasting blood sugars ≤ 160 mg/dL. Diabetic subjects who have recently had their glycemic control regimens adjusted and have documented fasting blood glucose concentrations ≤ 160 mg/dL may be considered, regardless of HgbA1c value, if per investigator discretion are considered to have adequate glycemic function • Negative pregnancy test (urine or serum) within 7 days prior to enrollment (women of child-bearing potential only) General • Plan to begin protocol specific therapy ≤ 7 days after enrollment |
|
E.4 | Principal exclusion criteria |
Disease Related • Symptomatic or untreated CNS metastasis - Subjects with CNS metastases that are both definitively treated and stably controlled are eligible if all of the following apply: 1) definitive therapy has been administered (surgery and/or radiation therapy); 2) there is no additional treatment planned for brain metastases; 3) the subject is clinically stable; and 4) the subject is off corticosteroids or on a stable dose of corticosteroids for at least 2 weeks prior to enrollment • Any prior or synchronous malignancy, except: - Malignancy treated with curative intent and with no known active disease present for ≥ 3 years prior to enrollment and felt to be at low risk for recurrence by the treating physician - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease - Adequately treated cervical carcinoma in situ without evidence of disease - Prostatic intraepithelial neoplasia without evidence of prostate cancer Cancer Therapy • Prior chemotherapy, chemo-radiation or investigational agent for the treatment of SCLC - Prior palliative radiotherapy to sites of distant metastasis is allowed (if completed ≥ 7 days prior to enrollment) - Prior treatment of CNS metastasis is allowed (as defined in Section 4.2.1) • Currently or previously treated with biological, immunological or other anti-tumor therapies for SCLC • Prior radiotherapy to > 25% of the bone marrow Medications/ Treatments • Recent infection requiring systemic anti-infective treatment that was completed ≤ 14 days prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection) Medical Conditions • History of bleeding diathesis • Current serious or non-healing wound or ulcer • Known positive test for human immunodeficiency virus, hepatitis C, chronic or active hepatitis B • Any clinically significant medical or psychiatric condition, co-morbid disease, addictive disorder, or laboratory abnormality (eg, cardiovascular disease or chronic obstructive pulmonary disease), which may increase the risks associated with study participation or study treatments or could interfere with the safe delivery of study treatment or increase risk of toxicity • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures • Major surgical procedure within 28 days prior to enrollment, or not yet recovered from major surgery • Minor surgical procedures within 7 days prior to enrollment, or not yet recovered from minor surgery Note: uncomplicated placement of vascular access device, fine needle aspiration, thoracocentesis or paracentesis ≥ 3 days prior to enrollment is acceptable General • Inability to tolerate IV drug administration • Subject is currently enrolled in or has not yet completed at least 30 days prior to enrollment since ending other investigational device or clinical study(s) • Subject of child-bearing potential is evidently pregnant (eg, positive human chorionic gonadotropin test) or is breast feeding • Woman or man with partner of childbearing potential not consenting to use adequate contraceptive precautions ie, double barrier contraceptive methods (eg, diaphragm plus condom), or abstinence during the course of the study and for 3 months after the last study drug administration for women, and 6 months for men • Subject has known sensitivity to any of the products to be administered during the study • Subject is not able to tolerate IV drug infusions • Subject unwilling or unable to comply with study requirements • Subject will not be available for follow-up assessments • Subject previously enrolled in this study |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Part 1: ▪ The incidence of adverse events and clinical laboratory abnormalities defined as DLT Part 2: ▪ OS |
|
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 | Yes |
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) | Yes |
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 | Yes |
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 | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Part 1 is open label, Part 2 is double blind placebo controlled |
|
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 |
|
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
|
The end of the clinical study is when all subjects have completed the study treatment and long term follow up (up to a maximum of 36 months from the date the last subject is randomised). This will allow long term assessment of disease status and survival. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |