E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced unresectable or metastatic Renal Cell Cancer in patients who have received no previous systemic anti-cancer treatment |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10050513 |
E.1.2 | Term | Metastatic renal cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
To compare the efficacy and safety of BIBF 1120 and sunitinib to treat patients with Renal Cell Cancer. An additional objective of the 1199.26 study is to assess the effects of BIBF 1120 treatment on the QTcF interval.
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E.2.2 | Secondary objectives of the trial |
Efficacy
• Progression Free Survival.
• Objective Tumour response.
• Duration of Objective Response.
• Overall Survival.
• Time to Treatment Failure.
• Time to Progression.
ECG - BIBF 1120 patients only
- Change of the QTcF interval from baseline to each patients maximum dose of BIBF 1120 concentration.
- Time averaged QTcF interval over 1 to 12 hours.
Safety
- Frequency of all Adverse Events, including laboratory parameters, graded by NCI-CTCAEv3.
- Dose related dose reductions and discontinuation rates.
- Number and duration of hospital stays due to Adverse Events.
Pharmacokinetics
- PK characteristics of BIBF 1120 after a single dose and at steady state (Day 15). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with unresectable or metastatic Renal Cell Cancer, who have received no previous systemic anti-cancer treatment.
• Histological-confirmed diagnosis of renal cell cancer with clear cell component.
• Age ≥ 18 years.
• ECOG Performance Score 0 or 1.
• Life expectancy of at least 3 months
• Must have measurable disease according to RECIST, i.e. presence of at least one target lesion according to RECIST criteria in a previously non-irradiated area.
• Serum creatinine < 2 x ULN.
• Written informed consent consistent with ICH-GCP guidelines.
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E.4 | Principal exclusion criteria |
• Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study.
• Major injuries, bone fracture and/or surgery within past 4 weeks or/ and planned surgical procedures during the study period.
• Hypersensitivity to BIBF 1120, sunitinib or the excipients of the study drugs.
• Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 12 months, congestive heart failure > NYHA II, serious cardiac arrhythmia).
• LV-EF (left ventricular ejection fraction) by ECHO or MUGA below local limits of normal.
• Hepatic function: total bilirubin outside of normal limits; ALT and AST > 1.5x upper limit of normal (ULN) in patients without liver metastasis. For patients with liver metastasis: total bilirubin outside of normal limits, ALT and AST > 2.5x ULN.
• Coagulation parameters: international normalised ratio (INR) > 2, prothrombin time (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN.
• Absolute neutrophil count (ANC) < 1500/ml, Platelets <100000/ml, Haemoglobin <9.0 g/dl.
• History of clinically significant haemorrhagic or thromboembolic event in the past 6 months.
• Known inherited predisposition to bleeds or to thrombosis.
• History of clinically significant haemoptysis within the last 3 months (more than one tea- spoon of fresh blood per day)
• Therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous device) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325 mg per day).
• Previous treatment for RCC with targeted agents (in particular including any antibody and any VEGF/VEGFR, EGFR and mTOR inhibitors), immunotherapy [Interferon (IFNα) or Interleukin-2 (IL-2)] or chemotherapy.
• Treatment with other investigational drugs or participation in another clinical study within the past 4 weeks before start of therapy or concomitantly with this study.
• Patients unable to comply with the protocol.
• Pregnancy or breast feeding.
• Active alcohol or drug abuse.
• Women of child bearing potential, or men who are able to father a child, unwilling to use a medically acceptable form of contraception during the study period.
• Symptomatic central nervous system (CNS) metastatis or leptomeningeal disease as documented by CT, MRI or analysis of cerebrospinal fluid requiring radiotherapy, steroids or anticonvulsive treatment.
• Radiotherapy within the previous 4 weeks.
• QTcF interval > 500 ms at screening.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Progression Free Survival in patients treated with either sunitinib or BIBF 1120.
2. For patients treated with BIBF 1120 only - Change from baseline to endpoint (Day 15) of the QTcF interval at each point in time |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Progression Free Survival.
• Objective Response according to the Response Evaluation Criteria in Solid Tumours (RECIST).
• Duration of Objective Response.
• Overall Survival.
• Time to Treatment Failure.
• Time to Progression.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Until last randomised patient stops treatment. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
The effect of BIBF 1120 on QTcF interval. |
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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 | 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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |