Sunitinib in Patients With Advanced Gastric Cancer and Treated With FOLFIRI

Adenocarcinoma Clinical Trial

— SUN-CASE  

Official title:

A Randomized, Placebo-controlled Phase II Trial Investigating SUNITINIB Versus Placebo in Patients With Chemorefractory Advanced Adenocarcinoma of the Stomach or Lower Esophagus Treated With Chemotherapy FOLFIRI

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01020630
• Other study ID #: 2009-02-SUN-Case
• Status: Completed
• Phase: Phase 2
• First received: November 23, 2009
• Last updated: May 13, 2014
• Start date: November 2009
• Est. completion date: July 2013

Study information

• Verified date: May 2014
• Source: Johannes Gutenberg University Mainz
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: July 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma

Intervention

Drug:
• Sunitinib
Sunitinib will be orally administered at 25 mg once daily (in the morning without regards to meals) for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks.
• Placebo
Placebo will be orally administered once daily (in the morning without regards to meals) for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks.

Locations

Country	Name	City	State
Germany	Gesundheitszentrum St. Marien	Amberg
Germany	Helios Klinikum Berlin-Buch	Berlin
Germany	Universitätsmedizin Berlin Charite	Berlin
Germany	Evangelisches Krankenhaus Bielefeld	Bielefeld
Germany	Kliniken Essen-Mitte	Essen
Germany	Universitätsklinikum Essen	Essen
Germany	Krankenhaus Nordwest	Frankfurt
Germany	Martin-Luther-Universität Halle-Wittenberg	Halle
Germany	MVZ für Innere Medizin in Hamburg-Eppendorf	Hamburg
Germany	Universitätsklinikum des Saarlandes	Homburg
Germany	Klinikum Ludwigsburg Medizinische Klinik I	Ludwigsburg
Germany	Universitätsmedizin Mainz, 1. Med. Klinik	Mainz	Rheinland-Pfalz
Germany	Technische Universität München	München
Germany	Universitätsklinikum Rostock Klinik für Innere Medizin	Rostock
Germany	Leopoldina-Krankenhaus der Stadt Schweinfurt gGmbH	Schweinfurt
Germany	Klinikum Weiden	Weiden

Sponsors (1)

Lead Sponsor	Collaborator
PD Dr Markus Möhler

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint is the Progression-free survival (PFS) according to RECIST V1.1.		Average time period: up to one year (participants are followed until progression or death)	No
Secondary	Objective response rate (CR + PR) according to RECIST		Average time period: up to one year (participants are followed until progression or death)	No
Secondary	Safety and tolerability		one year	Yes