| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| metastatic or locally advanced pancreatic cancer |
|
| 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 | 10033575 |
| E.1.2 | Term | Pancreas cancer |
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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 |
| The primary objective of this study is to evaluate whether the addition of sunitinib to gemcitabine prolongs the progression-free survival (PFS) compared to gemcitabine alone in patients with advanced pancreatic cancer. |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives are the characterization of additional efficacy outcomes and safety in the experimental arm sunitinib and gemcitabine and their exploratory comparison with the gemcitabine alone arm. Secondary efficacy endpoints are:
- objective response (OR)
- time-to-progression (TTP)
- overall survival (OS)
- time-to-treatment-failure (TTF)
- safety
Secondary safety endpoints are adverse events according to CTC AE v3.0, SAEs.
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Evaluation of gene expression changes in peripheral blood during chemotherapy with gemcitabine as potential biomarkers for its efficacy
As of April 2010 a separate sub-study, in the german study sites only, shall be conducted:
The aim of this sub-study is to evaluate gene expression changes in peripheral blood cells during chemotherapy with gemcitabine as potential biomarkers for its efficacy.
The nucleoside analogue gemcitabine has become a major drug for treatment of several malignancies, in particular for pancreatic cancer for which it is regarded as standard first-line therapy. Despite of the very poor prognosis for pancreatic cancer, there is a wide variability in the clinical efficacy of gemcitabine treatment with some patients living several years. The reasons for that are largely unknown and remain to be elucidated in order to facilitate therapy optimization and possibly further drug development. The attempt of this sub-study is to identify biomarkers which might account for the wide inter-individual response rates seen with gemcitabine treatment (Tibaldi et al. 2008; Kwon et al. 2006). More specifically, an analyze of changes in genexpression of selected target genes in whole blood of patients during therapy in relation to baseline status, i.e. acquired gemcitabine resistance,will be conducted. Until now, such analyses have mainly been performed in tumour tissue (Bergman et al. 2005; Ohhashi et al. 2008), but barely in peripheral blood which is accessible also during therapy. Expression of genes significantly changed during therapy should be correlated with outcome of the patients to assess relevance as therapeutic biomarker. In positive case, DNA genotyping of candidate genes should be performed to identify genetic markers predictive for therapeutic outcome of gemcitabine therapy. If such DNA markers could be identified they would help to decide which kind of therapy is expected to be effective for an individual patient.
Candidate genes include gemcitabine uptake and metabolism (e.g., DCK, CDA), DNA repair (ERCC1), apoptosis induction (e.g., BAX) and some distinct genes for which relation with gemcitabine function will be discovered during the next five years. Thorough genotyping by determination of tagging SNPs will be done for one or more genes with correlation between expression and therapy efficacy.
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|
| E.3 | Principal inclusion criteria |
(1) Adult males and females: over 18 years of age.
(2) Patients who suffer from locally advanced or metastatic pancreatic cancer
(3) Patients with measurable disease (at least one uni-dimensionally measurable target lesion by CT-scan or MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST).
(4) ECOG 0 or 1
(5) Signed written informed consent.
(6) White blood cell count (WBC) 3x10*9/L with neutrophils 1.5 x 10*9/L, platelet count 100x10*9/L, hemoglobin 5.6 mmol/L (9 g/dL).
(7) Total bilirubin 2 x upper limit of normal.
(8) AST and ALT 2.5 x upper limit of normal, or 5 x upper limit of normal in case of liver metastases.
(9) Serum creatinine 1.5 x upper limit of normal
(10) Anticoagulation treatment with heparin or low molecular weight heparin (LMWH): Patients will be allowed to participate provided that close monitoring of at least weekly evaluations are performed.
(11) Normal ECG without QT prolongation (QTc < 450 msec).
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|
| E.4 | Principal exclusion criteria |
(12) Resectable pancreatic cancer
(13) Previous chemotherapy (for adjuvant or metastatic disease)
(14) Any contraindication for gemcitabine chemotherapy regimen.
(15) Any investigational drug within the 30 days before inclusion.
(16) Prior use of sunitinib or other multitarget tyrosine kinase inhibitor
(17) Known or suspected allergy or hypersensitivity reaction to any of the components of study treatments.
(18) Pregnancy (absence to be confirmed by beta-hCG test) or lactation period.
(19) Men or women of child-bearing potential who are sexually active and unwilling to use a medically acceptable method of contraception from the start of treatment up 6 months after end of treatment.
(20) Clinically symptomatic brain or meningeal metastasis. (known or suspected)
(21) Cardiac arrhythmias requiring anti-arhythmics (excluding beta blockers or digoxin).
(22) History of any of the following cardiac events within the past 6 months:
- myocardial infarction (including severe/unstable angina)
- coronary/peripheral artery bypass graft
- symptomatic congestive heart failure (CHF) > NYHA Class II
- cerebrovascular accident or transient ischemic attack
- pulmonary embolism
(23) uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 90 mm Hg despite the use of 3 anti-hypertensive drugs
(24) Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease or chronic diarrhea
(25) Previous malignancy (other than pancreatic cancer) in the last 5 years except basal cell cancer of the skin, pre-invasive cancer of the cervix or superficial bladder tumor [Ta, Tis and T1].
(26) History of organ allograft
(27) Significant disease which, in the investigator`s opinion would exclude the patient from the study.
(28) Patients with seizure and epileptic disorder or other conditions requiring medication (such as phenytoin, carbamazepin, phenobarbital)
(29) Patients requiring long-term cortisone therapy
(30) Patients requiring oral anticoagulation treatment (such as marcoumar)
(31) Legal incapacity or limited legal capacity
(32) Known alcohol or drug abuse.
(33) Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent.
(34) Current fistula formation.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression-free-survival (PFS) |
|
| 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 | 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 11 |
| 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 | 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
| |
| 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 | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
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