E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Extensive or limited and sensitive or refractory SCLC after failure of first-line chemotherapy. |
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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 | 10041071 |
E.1.2 | Term | Small cell lung cancer stage unspecified |
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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 |
The primary objective is to demonstrate superiority in overall survival of amrubicin (40 mg/square metre administered as a 5-minute infusion once daily for 3 consecutive days starting on Day 1 of a 21-day course) compared with topotecan (1.5 mg/square metre administered as a 30-minute infusion once daily for 5 consecutive days starting on Day 1 of a 21-day course) in patients with extensive or limited and sensitive or refractory small cell lung cancer (SCLC) after failure of first-line chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
The important secondary objectives are to further characterize the clinical benefit of amrubicin compared with topotecan in terms of the following: • Objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST); • Progression-free survival (PFS); and • Duration of response. Additional secondary objectives are to assess or compare the effect of amrubicin relative to topotecan in terms of the following: • Time to tumor progression (TTP); • Quality of life (assessed using EuroQol [EQ-5D] and the Lung Cancer Symptom Scale [LCSS]); • Safety; and • Pharmacokinetics (plasma and whole blood concentrations) in amrubicin-treated patients only. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histological or cytological diagnosis of SCLC at study entry according to the International Association for the Study of Lung Cancer (IASLC) histopathologic classification. Mixed or combined subtypes according to the IASLC are not allowed;
2. SCLC that is either sensitive (defined as a response, including stable disease, to first-line platinum-based chemotherapy, with subsequent progression ≥ 90 days after completing first-line chemotherapy) or refractory (defined as progressive disease as best response to first-line platinum-based chemotherapy or progression < 90 days after completing first-line chemotherapy);
3. Extensive or limited disease; however, patients with limited disease who are candidates for local or regional salvage radiation therapy must have been offered such treatment prior to participation in this study;
4. Radiographically documented progression after first-line treatment with platinum-based chemotherapy;
5. No more than 1 prior chemotherapy regimen;
6. At least 18 years of age;
7. ECOG performance status of 0 or 1.
8. Measurable disease defined by modified RECIST as follows: a. Measurable disease: The presence of at least 1 measurable lesion, b. Measurable lesion: Lesions that can be accurately measured in at least 1 dimension with the longest diameter ≥ 20 mm using conventional techniques, or ≥ 10-16 mm, depending on reconstruction interval, using spiral computed tomography (CT) scans;
9. Adequate organ function including the following: a. Adequate bone marrow reserve: absolute neutrophil count (segmented and bands) (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, and hemoglobin ≥ 90 g/L, b. Hepatic: bilirubin ≤ 1.5 x the upper limit of normal (ULN), ALT and AST ≤ 3.0 x ULN, c. Renal: serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 60 mL/min, d. Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA);
10. Negative serum pregnancy test at the time of enrollment for females of childbearing potential;
11. For males and females of child-producing potential, use of effective contraceptive methods during the study;
12. Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, to understand and complete QoL forms, and agree to abide by the study restrictions and to return for the required assessments. |
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E.4 | Principal exclusion criteria |
Patients meeting any of the following criteria will be excluded from the study:
1. Pregnant or nursing females;
2. Chest radiotherapy with curative intent to the primary disease complex ≤ 28 days prior to first dose; cranial radiotherapy ≤ 21 days prior to first dose; radiotherapy to all other areas ≤ 7 days prior to first dose;
3. Prior anthracycline, topotecan or irinotecan treatment;
4. Treatment with any investigational agent within 28 days or standard chemotherapy within 21 days prior to first dose. Patients must have recovered from all acute adverse effects of prior therapies, excluding alopecia;
5. Patients with previous malignancy treated with chemotherapy and/or radiation (except in situ carcinoma of the cervix, localized low-grade prostate cancer, adequately treated non-melanomatous skin cancer, or ductal carcinoma in situ [DCIS] of the breast). Patients with a previous malignancy that was treated surgically at least 3 years prior and who have been in remission since that time will be allowed;
6. Concurrent severe or uncontrolled medical disease (eg, active systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the ability of the patient to complete the study;
7. Symptomatic central nervous system metastases. Patients with asymptomatic brain metastases are allowed. The patient must be stable for ≥ 2 weeks after radiotherapy ; if the patient is on corticosteroids, the dose of corticosteroids must have been stable for ≥ 2 weeks prior to first dose of study treatment, or be in the process of being tapered;
8. Suspected, diffuse idiopathic interstitial lung disease or pulmonary fibrosis not related to prior treatment.
9. Patients with known history of seropositive human immunodeficiency virus (HIV) or patients who are receiving immunosuppressive medications that would, in the opinion of the investigator, increase the risk of serious neutropenic complications.
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival will be the primary endpoint for this study |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 71 |
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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The end of the trial is defined as the date the last patient dies or is lost to follow-up.
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 4 |