E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically or cytologically confirmed diagnosis of gastric adenocarcinoma or gastroesophageal junction adenocarcinoma i.e. an adenocarcinoma with 50 extension in the stomach . Patients must present with stage IV disease not amenable to surgery, radiation, or combined modality therapy with curative intent. |
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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 | 10017940 |
E.1.2 | Term | Gastrointestinal carcinoma |
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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 |
To determine the antitumor activity of single-agent SU011248 at a dose of 50 mg orally once daily for 4 consecutive weeks repeated every 6 weeks in patients with advanced / metastatic gastric cancer, after failure of one prior chemotherapy regimen for advanced / metastatic disease. |
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E.2.2 | Secondary objectives of the trial |
. To assess measures of duration of tumor control . To evaluate the safety and tolerability of SU011248 . To explore the effects of SU011248 on patient reported outcomes of health related quality of life HRQOL and gastric cancer specific symptoms. . To evaluate SU011248 and SU012662 trough concentrations Ctrough and to correlate these plasma concentrations with activity and safety parameters . To explore the correlations of cancer biomarkers with cancer-and treatment-related outcomes |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial 1. Histologically or cytologically confirmed diagnosis of gastric adenocarcinoma or gastroesophageal junction adenocarcinoma i.e. an adenocarcinoma with 50 extension in the stomach . 2. Patients must present with stage IV disease not amenable to surgery, radiation, or combined modality therapy with curative intent. Patients previously undergoing local treatment surgery and/or radiation must have subsequently progressed or recurred. 3. Patients must present with disease progression or recurrence after treatment with one prior single agent or combination chemotherapy regimen for advanced / metastatic disease last dose / 4 weeks before study entry . Patients may have also received prior adjuvant therapy if recurrence occurred 6 months after adjuvant therapy completion. 4. Resolution of all acute toxic effects excluding alopecia of prior chemotherapy, or prior radiotherapy, or surgical procedure to National Cancer Institute NCI Common Terminology Criteria for Adverse Events CTCAE grade / 1. 5. Measurable disease according to RECIST. 6. Male or female, 18 years of age or older. 7. ECOG performance status / 1. 8. Adequate organ function as defined by the following criteria Absolute neutrophil count ANC / 1,500/ L Platelets / 100,000/ L Hemoglobin / 9.0 g/dL Serum aspartate aminotransferase AST; serum glutamate-oxalate transferase SGOT and serum alanine aminotransferase ALT; serum glutamate-pyruvate transferase SGPT / 2.5 x upper limit of normal ULN , / 5 x ULN if there is liver involvement secondary to tumor. Total serum bilirubin / 1.5 mg/dL / 2.2 mg/dL in presence of Gilbert s disease regardless of liver involvement secondary to tumor. Prothrombin time PT / 1.5 x ULN Serum creatinine / 1.5 x ULN. 9. Life-expectancy of / 3 months. 10. Signed and dated informed consent document indicating that the patient or legally acceptable representative has been informed of all pertinent aspects of the trial prior to enrollment. 11. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. |
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E.4 | Principal exclusion criteria |
Patients presenting with any of the following will not be included in the trial 1. More than one prior chemotherapy regimen for advanced / metastatic disease. 2. Major surgery or radiation therapy 4 weeks of starting the study treatment. Prior palliative radiotherapy to metastatic lesion s is permitted, provided there is at least one measurable lesion that has not been irradiated. 3. Prior radiation therapy to 25 of the bone marrow. 4. Presence of clinically relevant ascites i.e. requiring paracentesis and/or / NCI CTCAE Grade 2 weight loss. 5. NCI CTCAE Grade 3 hemorrhage 4 weeks of starting study treatment. 6. Inability to swallow oral medications, or presence of active inflammatory bowel disease, partial or complete bowel obstruction or chronic diarrhea. 7. Known brain metastases, or spinal cord compression, or carcinomatous meningitis baseline CT or magnetic resonance imaging MRI scan of the brain required only in case of clinical suspicion of central nervous system metastases . 8. Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri. 9. Any of the following within the 12 months prior to study drug administration severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, including transient ischemic attack, or pulmonary embolism. 10. Ongoing cardiac dysrhythmias of NCI CTCAE grade / 2, atrial fibrillation of any grade, or prolongation of the QTc interval to 450 msec for males or 470 msec for females. 11. Hypertension that cannot be controlled by medications blood pressure 150/90 mmHg despite optimal medical therapy . 12. Treatment with anticonvulsant agents and treatment with therapeutic doses of Coumadin currently or within 2 weeks prior to first day of SU011248 administration. Low dose coumadin for DVT prophylaxis is permitted up to 2 mg/day . Low molecular weight heparin is allowed. 13. Known human immunodeficiency virus HIV or acquired immunodeficiency syndrome AIDS -related illness. 14. Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test serum or urine within the 21 days prior to enrollment. 15. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study. 16. Prior treatment on a SU011248 trial. 17. Receipt of any investigational agent within 4 weeks prior to study entry. 18. Current treatment on another therapeutic clinical trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall confirmed objective response rate ORR as determined according to RECIST. |
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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 | No |
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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.8.5 | 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 |
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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
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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 | 0 |
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 | 0 |