Sunitinib in Patients With Advanced Gastric Cancer and Treated With FOLFIRI (SUN-CASE)

PD Dr Markus Möhler

Status and phase

Completed

Phase 2

Conditions

Adenocarcinoma

Treatments

Drug: Placebo

Drug: Sunitinib

Study type

Interventional

Funder types

Other

Identifiers

NCT01020630

2009-02-SUN-Case

Details and patient eligibility

About

This trial will be conducted to evaluate the efficacy, safety and tolerability of SUNITINIB as add-on therapy with a widely used second-line palliative FOLFIRI chemotherapy in patients with chemo-refractory advanced or metastatic adenocarcinoma of stomach or lower esophagus (mGC).

There is a clear scientific rationale for the use of Sunitinib to treat patients with mGC. Despite recent therapeutic advances, the median overall survival (OS) in patients with mG is still ≤ 12 months. Therefore, newer agents with novel mechanisms of action are desperately needed for treatment of these patients.

Full description

In parallel to the efforts in front-line therapy, second-line protocols like irinotecan-based regimens have been established in clinical trials for those patients. As many patients are still in good performance status and present with low tumor burden after failure of first-line chemotherapy, they clearly benefit from second-line treatment.

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.

The safety and efficacy of Sunitinib as single agent for the treatment of mGC has been determined and support the proposed clinical study with FOLFIRI in combination with Sunitinib in the treatment of patients with mGC.

Patients included in this trial suffer from advanced or metastatic adenocarcinoma of stomach or lower esophagus. They have failed to respond at least to one standard palliative first-line therapy (based on docetaxel and/or cisplatin plus 5-FU). Irinotecan/FA/5-FU can be determined as one established second-line treatment to be available for these patients.

Taken together, treatment of those patients with Sunitinib combined with standard chemotherapy FOLFIRI offers the chance to benefit from a new innovative therapy with acceptable side effects.

Enrollment

91 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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 criteria patients aged 18 years and older
karnofsky index 100 - 70 %
Life expectancy > 12 weeks
Adequate hematological, hepatic and renal functions
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)

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
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
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 ; 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; 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