| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Inoperable NSCLC, stages IIIB and IV |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10029521 |
| E.1.2 | Term | Non-small cell lung cancer stage IIIB |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10029522 |
| E.1.2 | Term | Non-small cell lung cancer stage IV |
|
| 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 |
|
| E.2.2 | Secondary objectives of the trial |
• Progression free survival, defined as the duration of time from first study treatment until progression or death from any cause as documented by the investigator.
• Overall survival, defined as the duration of time from first study treatment until death from any cause.
• Duration of response defined as timeframe from first response (CR or PR) until progression from best response.
• Overall toxicity according to NCI-CTC criteria.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Histologically or cytologically documented inoperable, locally advanced (Stage IIIB with supraclavicular lymph node metastases or malignant pleural or pericardial effusion), metastatic (Stage IV) or recurrent NSCLC other than squamous cell (i.e. adenocarcinoma or large-cell carcinoma, tumours of mixed histology should be categorized by the predominant cell type)
• At least 1 measurable lesion according to RECIST criteria
• ECOG performance score 0 or 1
• Life expectancy greater than 12 weeks
• Adequate organ functions in accordance with standard criteria (heart, kidney and liver functions as well as hematopoetic functions) as follows:
• Absolute neutrophile count (ANC) ≥ 1.500/µl AND platelet count ≥ 100.000/µl AND hemoglobin ≥ 9 g/dl (may be transfused to meet or exceed this level)
• Bilirubin ≤ 1,5 x ULN AND alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) ≤ 2,5 x ULN in patients without liver metastases; ≤ 5 x ULN in patients with liver metastases
• Creatinine clearance ≥ 60 ml/min, serum creatinine ≤ 1,25 x ULN AND proteinuria Dipstick < 2+. Patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤1 g of protein in 24 hours
• INR ≤1,5 and PTT ≤1,5 x ULN within 7 days prior to enrolment
• Age between 18 and 70 years.
• Ability to understand and comply with requirements of study protocol and trial participation
• Patients of child-bearing potential must have a negative pregnancy test at study entry and must agree to using a reliable means of contraception (e.g. physical barrier, contraceptive pill or patch, spermicide and barrier, or IUD) for the duration of the treatment including 2 months thereafter
• Signed informed consent
|
|
| E.4 | Principal exclusion criteria |
• Mixed, non-small cell and small cell tumours or mixed adenosquamous carcinomas with a predominant squamous component.
• History of haemoptysis, defined as bright red blood of at least half a teaspoon in the 3 months prior to enrolment.
• Evidence of tumour invading major blood vessels on imaging. The investigator or the local radiologist must exclude evidence of tumour that is fully contiguous with, surrounding, or extending into the lumen of a major blood vessel (e.g. pulmonary artery or superior vena cava).
• Previous neoadjuvant/adjuvant chemotherapy.
• Previous radiotherapy.
• Serious uncontrolled coagulation disorder or thrombo-embolic complications (history of embolisms or thromboses) within 6 months prior to study start or history of serious bleeding complications (haemorrhage).
• Major surgical procedures within 4 weeks prior to study entry or planned major surgical procedures throughout the course of the study. Patients must have fully recovered from any surgical procedures conducted prior to 4 weeks before study entry.
• Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion.
• Concurrent or recent (within 10 days) anticoagulant therapy. Prophylactic use of anticoagulants is allowed.
• Current acetylsalicylic acid medication > 325 mg or concurrent treatment with non-steroidal anti-inflammatory drugs (NSAIDs) known to affect platelets.
• Known hypersensitivity against any of the applied drugs or their excipients.
• History of other malignancies within 5 years prior to study entry, except for adequately treated in situ carcinoma of the cervix; basal or squamous cell skin cancer.
• History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance.
• Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg)
• Patients with a history of severe cardiac disease; e.g. NYHA Functional Class III or IV heart failure, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, or unstable angina.
• Non-healing wound, active peptic ulcer or bone fracture.
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment.
• Pregnant or breast feeding women. Women of child-bearing potential not using effective contraception. Men who do not agree to use effective contraception during the study and for a period of 60 days following the last administration of bevacizumab.
• Any co-existing medical condition that, in the investigator’s judgement, would preclude participation in the study or compromise patient’s ability to give informed consent.
• Treatment with any other investigational product or participation in another clinical study within 28 days prior to study start.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary objective of this proof-of-concept study is to determine the objective response rate in patients with unresectable, stage IIIB and IV non-small cell lung carcinoma treated with the combination cisplatin, docetaxel and bevacizumab. This response rate will be compared to historical data from the ECOG4599 and AVAiL trials. |
|
| 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 | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | No |
| 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 | Information not present in EudraCT |
| 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
|
| last visit of the last subject |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| 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 | 3 |
| 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 |
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