| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Chemorefractory metastatic adenocarcinoma of stomach, esophagogastric junction and lower esophagus (Barrett carcinoma) | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10017758 | | E.1.2 | Term | Gastric cancer | |
| 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 is to evaluate the antitumor activity of SUNITINIB administered as a single agent in patients with metastatic gastric cancer refractory to cisplatin- and/or irinotecan-based chemotherapy | |
| E.2.2 | Secondary objectives of the trial | The secondary objectives are:
-Effects of SUNITINIB on the time to tumor progression and
-effects of SUNITINIB on survival (one-year survival and overall survival)
-Safety and tolerability of SUNITINIB | |
| 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 | 1. Determination of tyrosine kinase receptors and their soluble ligands (date and version as the main protocol). Objective: prospective analysis the expression of tyrosine kinase dependent receptor pathways and their soluble ligands before and during SUNITINIB therapy; correlation with clinical outcome, responses and survival times.
2. Dynamic contrast magnetic resonance tomography (date and version as the main protocol). Objective: Explorative analysis of the efficacy of SUNITINIB to influence the tumor microcirculation with its blood flow and arterial permeability.
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| E.3 | Principal inclusion criteria | 1.Male and female patients aged 18 years and older
2.Signed and dated informed consent of the patient before the start of specific protocol procedures
3.Histologically proven adenocarcinoma of stomach, esophagogastric junction or lower esophagus (Barrett carcinoma)
4.Measurable metastatic disease according to the RECIST (33). If locally recurrent disease, it must be associated with at least one measurable lymph node (> 20 mm by CT scan or > 10 mm with spiral CT)
5.Failure of prior palliative chemotherapy/chemotherapies (at least one Irinotecan- or Cisplatin-based). Failure is defined either by progression of disease or by significant toxicity that precludes further treatment
6.At least 3 weeks from previous chemotherapy at first dose of study drug
7.Resolution of all acute toxic side effects of prior therapy or surgical procedures to grade ≤ 1 NCI-CTC criteria (except for the laboratory values)
8.Adequate organ function as defined by the following criteria:
•Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) 2.5 x upper limit of normal (ULN), or AST and ALT 5 x ULN if liver function abnormalities are due to underlying malignancy
•Total serum bilirubin 1.5 x ULN
•Absolute neutrophil count (ANC) 1500/L
•Platelets 100,000/L
•Hemoglobin 8.0 g/dL without support of growth factors (previous administration of erythrocyte concentrate is allowed)
•Serum calcium 12.0 mg/dL
•Serum creatinine 2.0 x ULN
•Lipase/Amylase ≤ 2,5 x ULN
•All other laboratory values specified in chaper 7.6: resolution of all side effects of prior therapy or surgical procedure to grade < 3 NCI CTC
9.At least 4 weeks from any major surgery (at first dose of study drug)
10.Karnofsky Performance Status (KPS) ≥ 70
11.Life expectancy > 12 weeks
12.Patients must be able to swallow SUNITINIB capsules
13.Patients who understand the nature of the trial and are willing and able to comply with scheduled visits, treatment plans, laboratory tests and other study procedures
14.Female patients who are capable of bearing children must have a negative pregnancy test result (serum or urine) at study entry. All women included in the study must be surgically sterile or postmenopausal or agree to employ adequate birth control measures for the duration of the study and six months post-dosing. Male patients must be surgically sterile or must agree to use effective contraception during the study and six months post-dosing (for details see chapter 7.7).
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| E.4 | Principal exclusion criteria | 1.Other tumor type than adenocarcinoma (e.g., leiomyosarcoma, lymphoma) or a second cancer except in patients with squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix which has been effectively treated. Patients curatively treated and disease free for at least 5 years will be discussed with the sponsor before inclusion
2.Patients with known brain or leptomeningeal metastasis
3.Intake of non-permitted concomitant drugs (the coordinating investigator should be contacted to discuss the individual case), see chapter 5.4:
•Concomitant treatment with antiarrhythmics and drugs with dysrhythmic potential (ie, terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, and indapamide)
•Administration of potent CYP34A inhibitors during or within 7 days before start of SUNITINIB-treatment (e.g. ketoconazole, itraconazole, clarithromycin, erythromycin, diltiazem, verapamil, delavirdine, indinavir, saquinavir, ritonavir, atazanavir, nelfinavir, grapefruitjuice)
•Administration of potent CYP3A4 inducers during or within 12 days before start of SUNITINIB-treatment (e.g. dexamethason, rifampicin, rifabutin, carbamazepine, phenobarbital, phenytoin, St. John´s wort, efavirenz, tipranavir
•Ongoing treatment with therapeutic doses of anticoagulants such as Coumadin or heparins (however, low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed)
•Any other medicinal anticancer therapy during treatment phase except treatment with non-conventional therapies (e.g. herbs or acupuncture) and vitamins/mineral supplements, provided that they do not interfere with the study endpoint, in the opinion of the investigator
•Concurrent systemic immune therapy, chemo- or hormone therapy
•Concomitant or within a 4-week period administration (from first dose of study drug) of any other experimental drug under investigation (except of Irinotecan and Cetuximab) and participation in another clinical trial
4.Any prior radiotherapy of target lesions
5.Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (> hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis
6.Current history of chronic diarrhoea
7.Active disseminated intravascular coagulation, or patients prone to thromboembolism
8.Any of the following events (in any grade) prior to starting the trial treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
9.Known history of QT interval prolongation, ongoing QT prolongation (>450 msec for males or >470 msec for females), any cardiac ventricular dysrhythmias, atrial fibrillation of any grade
10.Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy)
11.Known human immunodeficiency virus (HIV) infection
12.Active uncontrolled infection
13.Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into the trial
14.Pregnant or lactating women
15.Known allergic/hypersensitivity reaction to any of the components of the treatment; or known drug abuse/alcohol abuse
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| E.5 End points |
| E.5.1 | Primary end point(s) | The primary endpoint is the objective response rate within the first six treatment cycles defined as the percentage of patients with a confirmed reduction in tumor size compared to baseline fulfilling the criteria for complete or partial response as defined in chapter 7.8.
The response is measured by CT.
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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 | 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 | 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) | No |
| E.8.2.2 | Placebo | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| 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 | 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 | Collection of data will be stopped one year after the recruitment of the last patient
Patients who responded to treatment (including Stable Disease) and are still on study medication at this timepoint will be treated within the study with SUNITINIB study medication until progression of disease or until untolerable side effects occur. The therapy will be supervised by the local investigator. | |
| 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 | 6 |
| 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 | 6 |
