Imatinib, Capecitabine, and Cisplatin in Treating Patients With Unresectable or Metastatic Stomach Cancer

This study has been completed.
Sponsor:
Information provided by:
Technische Universität München
ClinicalTrials.gov Identifier:
NCT00601510
First received: January 25, 2008
Last updated: March 18, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Gastric Cancer
Drug: capecitabine
Drug: cisplatin
Drug: imatinib mesylate
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Capecitabine, Cisplatin and Imatinib in Patients With Unresectable or Metastatic Gastric Cancer.

Resource links provided by NLM:


Further study details as provided by Technische Universität München:

Primary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]
  • Tolerability [ Designated as safety issue: Yes ]
  • Overall tumor response as assessed by RECIST [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression of disease [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Quality of life [ Designated as safety issue: No ]

Enrollment: 38
Study Start Date: November 2007
Study Completion Date: January 2012
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imatinib mesylate
Imatinib mesylate 300mg/day(maximum dose will be 800 mg) on day -4, -3, -2, -1, 1, 2, 3 through d21 in combination with capecitabine 1250 mg/m2 twice daily (d1-d14) and iv cisplatin 60mg/m2
Drug: capecitabine Drug: cisplatin Drug: imatinib mesylate

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00601510

Locations
Germany
Klinikum Rechts Der Isar - Technische Universitaet Muenchen
Munich, Germany, D-81675
Sponsors and Collaborators
Technische Universität München
Investigators
Study Chair: Matthias Ebert, MD Technische Universität München
  More Information

Additional Information:
No publications provided by Technische Universität München

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00601510     History of Changes
Other Study ID Numbers: CDR0000581134, KRDI-TUM-STI571, KRDI-TUM-GLIVEC-CSTI571BDE54, EU-20797, NOVARTIS-KRDI-TUM-STI571, EUDRACT-2006-005792-17
Study First Received: January 25, 2008
Last Updated: March 18, 2013
Health Authority: United States: Federal Government

Keywords provided by Technische Universität München:
stage III gastric cancer
stage IV gastric cancer

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Imatinib
Capecitabine
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 21, 2014