clinical trial for treatment of advanced cancer of the lower esophagus and stomach, with the Sunitinib or Placebo in addition to standard therapy

• Conditions: Chemo-refractory advanced or metastatic adenocarcinoma of stomach or lower esophagus; MedDRA version: 14.1Level: LLTClassification code 10001173Term: Adenocarcinoma of esophagusSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10007474Term: Carcinoma stomachSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2009-014336-38-DE
• Lead Sponsor: niversitätsmedizin der Johannes Gutenberg-University Mainz

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-08-20
• Last Update Posted: 23 September 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

•Signed and dated informed consent before the start of specific protocol procedures;
•Histological proven gastric adenocarcinoma including adenocarcinoma of the esophagogastric junction or lower esophagus;
•Failure of any prior chemotherapy (docetaxel and/or platinum-based chemotherapy); but patient has not previously received FOLFIRI treatment;
•Measurable metastatic disease according to the RECIST 1.1 criteria. 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);
•Age: = 18 years;
•Karnofsky index 100 – 70 %
•Life expectancy > 12 weeks;
•Adequate hematological, hepatic and renal functions: ANC = 1.5 x 109/L, platelets = 100 x 109/L; creatinine = 2 x UNL; total bilirubin = 3 x UNL, AST (SGOT) and ALAT (SGPT) = 3 x UNL; in case of liver metastases: total bilirubin = 6 x UNL, AST (SGOT) and ALAT (SGPT) = 6 x UNL;
•At least 3 weeks from previous docetaxel– and/or platinum-based chemotherapy;
•Recovery from hematological side effects (CTC grade < 1) and non-hematological side effects (CTC grade = 1) of any prior therapy (except oxaliplatine induced neuropathy CTC grade = 2);
•Able to comply with scheduled assessments and with management of toxicity;

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

Exclusion Criteria

•History of another primary malignancy =3 years, with the exception of non-melanoma skin cancer and in situ carcinoma of the uterine cervix;
•Any prior palliative radiotherapy of the target lesions;
•Concurrent treatment with any other medicinal anti-cancer therapy;
•Prior treatment with a VEGF, VEGFR or RTK inhibitor, or prior enrolment on this study (some inhibitors may be allowed after obtaining Sponsor approval);
•Known allergic/hypersensitivity reaction to any of the components of the treatment;
•Treatment with potent CYP3A4 inhibitor within 7 days of Sunitinib/placebo dosing or with potent CYP3A4 inducer within 12 days of Sunitinib/placebo dosing; except dexamethasone for the prevention of chemotherapy induced emesis;
•Other serious illness or medical conditions within the last 12 months prior to study drug administration:
-Unstable cardiac disease despite treatment; myocardial infarction within 12 months prior to study entry; congestive heart failure NYHA grade 3 and 4;
-Hypertension that cannot be controlled by medication (>150/100 mmHg) despite optimal medical therapy;
-Ongoing cardiac dysrhythmias of NCI CTCAE grade = 2, atrial fibrillation of any grade, or QTc interval >450 msec for males or >470 msec for females;
-History of significant neurologic or psychiatric disorders including dementia or seizures;
-Active uncontrolled infection;
-History of clinically significant bleeding within the past 6 months, including hemoptysis or haematuria, or underlying coagulopathy;
-Active disseminated intravascular coagulation;
-Cerebrovascular accident including transient ischemic attack;
-Pulmonary embolus;
-Bowel obstruction or chronic diarrhoea, history or presence of inflammatory enteropathy or extensive intestinal resection (> hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis;
-Peptic ulcer disease;
-History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrolment, unless affected area has been removed surgically;
•Known deficit in DPD;
•Hypercalcemia not controlled by bisphosphonates;
•Contraindications to the use of atropine;
•Pregnant or lactating women; female patients who are pregnant or lactating or men and women of reproductive potential not willing or not able to employ an effective method of birth control/contraception to prevent pregnancy during treatment and for 3 months after discontinuing study treatment;
•Known drug abuse/alcohol abuse;
•Current, recent, or planned participation in an experimental treatment drug study other than this protocol;
•Major surgical procedure, open biopsy or significant traumatic injury within 4 weeks before starting treatment; anticipation of need for major surgical procedure (e.g. impending bowel obstruction) during the course of the study;
•History of other medical or psychiatric condition, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the patient at high risk from treatment complications.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to evaluate the progression-free survival (PFS) according to RECIST 1.1 in patients with chemo-refractory advanced or metastatic adenocarcinoma of stomach or lower esophagus and FOLFIRI-based chemotherapy.;Secondary Objective: •Objective response rate (CR + PR)<br>•Tumor control rate<br>•Duration of disease stabilisation<br>•1-year overall survival<br>•Overall survival<br>•Safety and tolerability of placebo-controlled combination therapy in comparison to standard second line therapy<br>;Primary end point(s): Progression-free survival (PFS) according to RECIST 1.1;Timepoint(s) of evaluation of this end point: The response to treatment is measured by computer tomography (CT) after every cycle.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Objective response rate (CR + PR) according to RECIST 1.1<br>•1-year survival<br>•Safety (according to NCI-CTCAE V4.0) and tolerability<br>•Progression-free survival rate: The time from first intake/dose of trial medication to first documentation of objective tumour progression or to death due to any cause, whichever occurs first.<br>•1-year survival: rate of subjects surviving for at least one year after first intake/dose of trial medication.<br>•Overall survival: the time between first applications of trial medication to date of death due to any cause. <br><br>;Timepoint(s) of evaluation of this end point: The response to treatment is measured by computer tomography (CT) after every cycle.