| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Locally advanced (stage IIIb with supraclavicular lymph node metastases or malignant pleural or pericardial effusion), metastatic or recurrent non squamous non-small cell lung cancer (NSCLC) |
|
| 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 |
|
| 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 assess the efficacy measured by progression free survival (PFS), of the combination of bevacizumab and pemetrexed as maintenance therapy versus bevacizumab alone, after a first line chemotherapy with cisplatin/pemetrexed and bevacizumab. |
|
| E.2.2 | Secondary objectives of the trial |
bevacizumab alone as maintenance therapy, measured by response rates, disease control rates, duration of response, and overall survival (OS).
To assess the safety of the combination of bevacizumab and pemetrexed as first line treatment and in maintenance therapy.
To assess quality of life (QOL) during maintenance therapy comparing bevacizumab in combination with pemetrexed versus bevacizumab alone.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Age ≥ 18 years.
- 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 non-squamous NSCLC.
- At least 1 unidimensionally measurable lesion meeting RECIST criteria (at least 10 mm in longest diameter [LD] by spiral computerized tomography [CT] scan, or at least 20 mm by standard techniques). Positron emission tomography (PET) scans and ultrasounds may not be used for tumor measurements.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2.
- Life expectancy ≥16 weeks.
- Adequate hematological function:
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L AND
Platelet count ≥ 100 x 109/L AND
Hemoglobin ≥ 9 g/dL (may be transfused to maintain or exceed this level).
- Adequate liver function:
Total bilirubin < 1.5 x upper limit of normal (ULN) AND
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 2.5 x ULN in patients without liver metastases; < 5 x ULN in patients with liver metastases.
- Adequate renal function:
Calculated creatinine clearance according to the formula of Cockroft and Gault ≥ 50 mL/min AND
Urine dipstick for proteinuria < 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.
- International normalized ratio (INR) ≤ 1.5 and activated prothrombin time (aPPT) ≤ 1.5 x ULN within 7 days prior to enrolment.
- Female patients should not be pregnant or breast-feeding. Female patients with childbearing potential should agree to use effective, non hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) during the study and for a period of at least 6 months following the last administration of study drugs. Female patients with an intact uterus (unless amenorrhoeic for the last 24 months) must have a negative serum pregnancy test within 7 days days prior to enrolment into the study.
- Fertile male patients must agree to use effective contraception during the study and for a period of at least 6 months following the last administration of study drugs. |
|
| E.4 | Principal exclusion criteria |
1.Mixed, non-small cell and small cell tumors or mixed adenosquamous carcinomas with predominant squamous component.
2.Prior chemotherapy or treatment with other systemic anti-cancer agent for lung cancer (including monoclonal antibodies or tyrosine kinase inhibitors), except for adjuvant chemotherapy if completed more than 3 years before enrolment.
3.Malignancies other than NSCLC within 5 years before randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, DCIS treated surgically with curative intent.
4.History of haemoptysis ≥ grade 2 (bright red blood of at least 2.5 mL within prior 3 months).
5.Evidence of tumor invading major blood vessels.
6.Radiotherapy to any site for any reason within 28 days prior to enrolment, except for palliative radiotherapy to bone lesions within 14 days prior to enrolment.
7.Surgery (including open biopsy), significant traumatic injury within prior 28 days or anticipatied need for major surgery during study treatment.
8.Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to first bevacizumab dose.
9.Current or recent (within 10 days prior to first dose of bevacizumab) use of aspirin (> 325 mg/day), or full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes. Prophylactic use of anticoagulants is allowed.
10.Patient unable or unwilling to take folic acid, vitamin B12 or corticosteroids.
11.Clinically detectable third-space fluid collections, e.g. ascites or pleural effusions that cannot be controlled prior to study entry.
12.History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
13.Uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg).
14.Clinically significant (i.e. active) cardiovascular disease, e.g., CVA (≤ 6 months before enrolment), MI (≤ 6 months before enrolment), unstable angina, CHF NYHA Class ≥ II, serious cardiac arrhythmia requiring medication that might interfere with administration of the study treatment, or not controlled by medication.
15.Non-healing wound, active peptic ulcer or bone fracture.
16.History of abdominal fistula, GI perforation or intra abdominal abscess within 6 months of enrolment.
17.Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment.
18.Known hypersensitivity to bevacizumab, any of its excipients, or any of the study drugs.
19.Evidence of other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression free survival, defined as the time period from randomization to the date of first occurrence of investigator assessed disease progression. |
|
| 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) | Information not present in EudraCT |
| 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) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| 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
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 18 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| 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 | 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
|
|
| 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 | 3 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 3 |
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