| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic pancreatic cancer (adenocarcinoma) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | PT |
| E.1.2 | Level | 7.1 |
| E.1.2 | Classification code | 10033610 |
|
| 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 demonstrate an increase in the duration of overall survival when bevacizumab is added to gemcitabine and erlotinib. |
|
| E.2.2 | Secondary objectives of the trial |
- To compare the Clinical Benefit Response (CBR) rate
- To compare the duration of Progression Free Survival (PFS)
- To compare the Disease Control Rate (DCR)
- To determine the safety and tolerability when bevacizumab is added to gemcitabine and erlotinib
- To determine the population pharmacokinetics of bevacizumab in the presence of gemcitabine and erlotinib |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Age ≥ 18 years
2. Able to comply with the protocol
3. Karnofsky Performance Status of ≥ 60%
4. Life expectancy of ≥ 8 weeks
5. Written informed consent
6. Histologically or cytologically documented pancreatic cancer (adenocarcinoma) with measurable or non-measurable metastatic disease (stage IV) according to the 6th edition of the TNM classification
7. Adequate bone marrow function: ANC ≥ 1.5 x 10[9]/L, platelet count ≥ 100 x 10[9]/L and Hb ≥ 9 g/dL
8. INR ≤ 1.5 and aPTT ≤ 1.5 x ULN within 7 days prior to randomisation
9. Adequate liver function:
- Serum (total) bilirubin ≤ 1.5 x ULN
- AST, ALT ≤ 2.5 x ULN in patients without liver metastases, ≤ 5 x ULN in patients with liver metastases
- Albumin ≥ 2.5 g/dL
10. Adequate renal function:
- Serum creatinine ≤ 2.0 mg/dL or 177 µmol/L
- Urine dipstick for proteinuria < 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline, who demonstrate ≤ 1 g of protein/24 hr on 24 hour urine collection
|
|
| E.4 | Principal exclusion criteria |
1. Local (Stage IA to IIB) pancreatic cancer and locally advanced (stage III) pancreatic cancer. Patients relapsing with metastatic disease, after initial diagnosis with local or locally advanced disease can be enrolled into this study
2. Previous adjuvant radiotherapy for pancreatic cancer, except for patients with progressive lesions outside the radiation port who completed the radiotherapy at least 6 months prior to study entry.
3. Less than (or equal to) six months since last adjuvant chemotherapy. Adjuvant therapy with gemcitabine (any dose > 350 mg/m[2]/week), EGFR-TKI or anti-VEGF based adjuvant therapy is not allowed. Patient must have recovered from all treatment related toxicities prior to randomisation and must have documented evidence of disease progression (metastatic) following adjuvant chemotherapy
4. Previous systemic therapy for metastatic pancreatic cancer
5. Other primary tumour (including primary brain tumours) within the last 5 years prior to randomisation, except for adequately treated carcinoma in situ of the cervix or basal cell skin cancer
6. Evidence of spinal cord compression or current evidence of CNS metastases (unless adequately treated). CT/MRI of the brain is mandatory (within 4 weeks prior to randomisation) in case of clinical suspicion or evidence of brain metastases
7. History or evidence, upon neurological exam, of other CNS disease (unless adequately treated with standard medical therapy), e.g. uncontrolled seizures
8. CT-scan based evidence of tumour invading major blood vessels (putting patients at risk of bleeding during study treatment)
9. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgery during the course of the study treatment
10. Current or recent (within 10 days of 1st dose of study treatment) chronic use of aspirin (>325 mg/day)
11. Current or recent (within 10 days of 1st dose of study treatment) chronic use of full therapeutic dose of oral or parenteral anticoagulants or thrombolytic agents
12. Uncontrolled hypertension or clinically significant (i.e. active) cardiovascular disease: CVA/stroke (≤ 6 months prior to randomisation), myocardial infarction (≤ 6 months prior to randomisation), unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
13. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
14. Non-healing wound, ulcer, or bone fracture, patients with oesophageal varices
15. Any known significant ophthalmologic abnormalities of the surface of the eye (the use of contact lenses is not recommended)
16. Inability to take oral medication, prior surgical procedures affecting absorption or resulting in the requirement for iv alimentation or parenteral nutrition with lipids
17. Pregnant or lactating females. Serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start
18. Men and women of childbearing potential (<2 years after last menstruation) not using effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile)
19. Current or recent (within the 30 days prior to starting study treatment) treatment with another investigational drug or participation in another investigational study
20. Evidence of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug, or patient at high risk from treatment complications
21. Known hypersensitivity to any of the study drugs or its ingredients |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary analysis of duration of survival will be performed after approximately 451
deaths have been observed. At this point in time, all efficacy and safety parameters will be analysed and a final study report will be written. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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) | 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 primary analysis of duration of survival will be performed after approximately 451 deaths have been observed. At this point in time, all efficacy and safety parameters will be analysed and a final study report will be written. |
|
| 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 | 9 |
| 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 | 9 |
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