GC-SU-2006 (SUNITINIB)

An Open-Label, Multicenter Phase II Trial of SUNITINIB for Patients With Chemo-Refractory Metastatic Gastric Cancer

Rekrutierung

Die Studie rekrutiert aktuell Patienten.

Studiendesign

open-label, multi-center, Phase II

Studienziel

Primary Outcomes: Objective response rate (CR + PR). Secondary Outcomes: Progression-free survival; 1-year survival; Overall survival; Safety and tolerability

Synopsis

This trial will be conducted to evaluate the efficacy, safety and tolerability of SUNITINIB as a second-line palliative therapy in metastatic gastric cancer. Despite the efforts in front-line therapy, second-line protocols have not yet been established in randomized clinical trials for those patients. However, as many patients are still in good performance status and present with low tumor burden after failure of first-line chemotherapy, they may clearly benefit from second-line treatment. Even more, increasingly more metachronic metastatic patients urge for new platinum-free therapeutic options due to the fast-growing use of (neo-) adjuvant platin-based protocols. So far, only sparse data on chemotherapy are available after failure of platin-based protocols. Nearly only irinotecan-containing combinations have properly been analyzed, and produced excellent response rates and survival times of up to 30% and 7.6 months, respectively. However, Irinotecan has not been approved yet for this indication. In addition, as irinotecan-containing regimen has been submitted for approval for first-line therapy, second-line regimens in irinotecan-refractory patients have not been evaluated in any trial. Thus, there is an urgent need to establish new second-line treatment options for both, cisplatinum- or irinotecan-combination refractory patients with advanced or metastatic gastric cancer. Sunitinib inhibits the receptor tyrosine kinases (RTKs) involved in tumor proliferation and angiogenesis, specifically the VEGFR, PDGFR, KIT, FLT-3, and RET. The VEGF pathway has been shown to be a significant factor in metastatic gastric cancer. In gastric carcinoma cells, VEGF ligands and its receptors are definitely involved in the process of tumor progression. KDR and Flt-1 are expressed widely and VEGF stimulated KDR-positive tumor cell growth directly. The ligand VEGF-C has also been shown to be involved in progression of human gastric carcinoma, particularly via lymphangiogenesis. In addition, peritoneal metastases of some cancers such as gastric cancers were largely dependent on VEGF. Therefore patients with chemo-refractory metastatic gastric cancer might benefit from VEGFR inhibitory therapy with SUNITINIB.

Einschlusskriterien

  • Signed and dated informed consent of the patient before the start of specific protocol procedures
  • Histologically proven adenocarcinoma of stomach, esophagogastric junction or lower esophagus (Barrett carcinoma)
  • 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)
  • Failure of one prior palliative chemotherapy (Irinotecan- or Cisplatin-based). Failure is defined either by progression of disease or by significant toxicity that precludes further treatment
  • At least 3 weeks from previous (Irinotecan- or Cisplatin-based) chemotherapy at first dose of trial drug
  • Female patients who are capable of bearing children must have a negative pregnancy test result (serum or urine) at trial entry. All women included in the trial must be surgically sterile or postmenopausal or agree to employ adequate birth control measures for the duration of the trial and six months post-dosing. Male patients must be surgically sterile or must agree to use effective contraception during the trial and six months post-dosing
  • Resolution of all acute toxic side effects of prior therapy or surgical procedures to grade ≤ 1 NCI-CTC (except for the laboratory values)
  • 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/microL, platelets ≥ 100,000/microL, 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 chapter 7.6: resolution of all side effects of prior therapy or surgical procedure to grade < 3 NCI CTC
  • At least 4 weeks from any major surgery (at first dose of trial drug)
  • Karnofsky Performance Status (KPS) ≥ 70
  • Life expectancy > 12 weeks
  • Patients must be able to swallow SUNITINIB capsules

Ausschlusskriterien

  • 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
  • Patients with known brain or leptomeningeal metastasis
  • More than one palliative chemotherapy before start of trial
  • 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)
  • Any prior radiotherapy of target lesions
  • Current history of chronic diarrhoea
  • Active disseminated intravascular coagulation, or patients prone to thromboembolism
  • 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
  • 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
  • Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy)
  • Known human immunodeficiency virus (HIV) infection
  • Active uncontrolled infection
  • 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 trial participation or trial drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into the trial
  • Pregnant or lactating women
  • Known allergic/hypersensitivity reaction to any of the components of the treatment; or known drug abuse/alcohol abuse

ClinicalTrials

Die Studie ist bei ClinicalTrials.gov unter der Registrierungsnummer NCT00411151 angemeldet.
Studieninformationen bei ClinicalTrials.gov

Studienassistentin

Frau Gröger, Telefon: 06131 17-5543

Studienleiter

Herr Dr. habil. Markus Möhler

Leiter der klinischen Prüfung

Herr Dr. habil. Markus Möhler
I. Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität Mainz
Tel. 06131 17-5712
E-Mail