Clinical trial NCT00601510: Imatinib, Capecitabine, and Cisplatin in Treating Patients With Unresectable or Metastatic Stomach Cancer
Official title: A Phase I Study of Capecitabine, Cisplatin and Imatinib in Patients With Unresectable or Metastatic Gastric Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastric Cancer
Keywords: stage III gastric cancer
stage IV gastric cancer
Lead sponsor: Technical University of Munich
Sponsor class: OTHER
First posted: 2008-01-28
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Imatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as capecitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imatinib together with combination chemotherapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of imatinib when given together with capecitabine and cisplatin in treating patients with unresectable or metastatic stomach cancer.

Detailed description: OBJECTIVES:

Primary

* To determine the maximum tolerable dose and assess the safety and tolerability of imatinib mesylate in combination with capecitabine and cisplatin in patients with unresectable or metastatic gastric cancer.

Secondary

* To assess the preliminary antitumor activity of this regimen in these patients.
* To assess the response with regard to the expression and/or mutation of the tyrosine kinase receptors PDGF-R and c-kit in gastric cancer.

OUTLINE: This is a dose-escalation study of imatinib mesylate.

Patients receive oral imatinib mesylate once daily on days -4 to 21 in course 1 and on days 1-21 in all subsequent courses, oral capecitabine twice daily on days 1-14, and cisplatin IV on day 1. Courses repeat every 3 weeks\* for 12 months in the absence of disease progression or unacceptable toxicity.

NOTE: \*First course is 25 days.

After completion of study therapy, patients are followed every 3 weeks.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed gastric cancer

  * Unresectable and/or metastatic disease
* Incurable with any conventional multimodality approach by interdisciplinary assessment of the local tumor board
* Immunohistochemical documentation of c-kit (CD117) and PDGF-R overexpression by tumor if obtainable (preferably on a tumor sample taken within 6 weeks of study entry)
* At least one evaluable site of disease according to RECIST criteria
* No known brain metastasis or CNS disorder that might alter study compliance or may worsen during or following therapy

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* WBC ≥ 3,000/μL
* ANC ≥ 2,000/μL
* Platelet count ≥ 100,000/μL
* Hemoglobin ≥ 9.0 g/dL
* Total bilirubin \< 2 times upper limit of normal (ULN)
* SGOT and SGPT \< 2.5 times ULN (5 times ULN if hepatic metastases present)
* Glomerular filtration rate ≥ 60 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective barrier contraception during and for up to 3 months after completion of study treatment
* No known or documented hypersensitivity against fluoropyrimidines, tyrosine kinase inhibitors, cisplatin, other platinums, or their respective derivatives
* No gastrointestinal disorder that might affect the gastrointestinal absorption of capecitabine or imatinib mesylate or ability to swallow for the oral administration of capecitabine or imatinib mesylate
* At least 5 years since prior primary malignancy except if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or carcinoma in situ of the cervix
* No other concurrent malignant disease
* No NYHA class III-IV cardiac disease (i.e., congestive heart failure or myocardial infarction within the past 6 months)
* No severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection)
* No known neuropathy, impaired hearing, history of seizures, and/or psychiatric disorder that might alter study compliance or may worsen during or following therapy
* No documented dihydropyrimidine dehydrogenase deficiency
* No known chronic liver disease (i.e., chronic active hepatitis or cirrhosis)
* No known diagnosis of HIV infection or other serious uncontrolled infections
* No significant history of non-compliance to medical regimens or inability to grant reliable informed consent

PRIOR CONCURRENT THERAPY:

* No chemotherapy or investigational agents within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C) unless the disease is rapidly progressing
* No prior radiotherapy to ≥ 25% of the bone marrow
* No major surgery within the past 2 weeks
* No concurrent warfarin or acetaminophen

  * Therapeutic anticoagulation using heparin or low-molecular weight heparin allowed
* No concurrent sorivudine or related substances
* No other concurrent anticancer agents, including chemotherapy and biologic agents
* No other concurrent investigational drugs

Primary outcomes:
measure: Safety
measure: Tolerability
measure: Overall tumor response as assessed by RECIST
Secondary outcomes:
measure: Time to progression of disease
measure: Overall survival
measure: Quality of life
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Klinikum Rechts Der Isar - Technische Universitaet Muenchen
Study officials:
affiliation: Technical University of Munich
name: Matthias Ebert, MD
role: STUDY_CHAIR
References:
citation: Mayr M, Becker K, Schulte N, Belle S, Hofheinz R, Krause A, Schmid RM, Rocken C, Ebert MP. Phase I study of imatinib, cisplatin and 5-fluoruracil or capecitabine in advanced esophageal and gastric adenocarcinoma. BMC Cancer. 2012 Dec 10;12:587. doi: 10.1186/1471-2407-12-587.