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Phase I Study of Imatinib, Gemcitabine and Capecitabine in Patients With Solid Tumors

Phase 1
19 Years
Open (Enrolling)
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase I Study of Imatinib, Gemcitabine and Capecitabine in Patients With Solid Tumors



- Determine the maximum tolerated dose of gemcitabine hydrochloride and capecitabine when
combined with imatinib mesylate in patients with advanced solid tumors.

- Determine the toxicity of this regimen in these patients.


- Explore the antitumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of gemcitabine and capecitabine.

Patients receive oral imatinib mesylate once daily on days 1-5 and 8-12, gemcitabine
hydrochloride IV on days 3 and 10, and oral capecitabine twice daily on days 1-14. Treatment
repeats every 21 days for at least 2 courses in the absence of progressive disease or
unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and
capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the
dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Existing paraffin-embedded tissue blocks from patients diagnosed with melanoma or renal cell
carcinoma will be assessed for c-kit mutations by polymerase chain reaction and direct
sequencing of both juxtamembrane domains (exons 9 and 11) and tyrosine kinase domain (exon
13 and 17). (Begins 12-11-2008)

PROJECTED ACCRUAL: Closed to patient accrual 12/11/2008.

Inclusion Criteria


- Histologically confirmed solid tumor, meeting 1 of the following criteria:

- Failed standard therapy and subsequent line therapy

- Disease for which no standard therapy exists

- Any number of prior therapies are allowed provided standard treatment options have
either been exhausted or are unable to be administered, in the opinion of the
treating physician

- Measurable or nonmeasurable disease

- Measurable disease is defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm
by CT scan or ≥ 10 mm by spiral CT scan

- Nonmeasurable disease is defined as all other lesions, including small lesions
(< 20 mm by conventional techniques or < 10 mm by spiral CT scan) and truly
nonmeasurable lesions, including the following:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural or pericardial effusion

- Lymphangitis cutis/pulmonis

- Abdominal masses that are not confirmed and followed by imaging techniques

- Cystic lesions

- Brain metastases allowed provided both of the following are true:

- Patient has undergone resection and/or radiotherapy and does not require

- No evidence of disease progression by CT scan or MRI at least 4 weeks after
completion of steroids, surgery, and/or radiotherapy


- ECOG performance status 0-2

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 8.5 g/dL (epoetin alfa supplementation allowed)

- Bilirubin ≤ 1.5 times upper limit of normal (ULN) (except if due to Gilbert's

- AST and ALT ≤ 2.5 times ULN

- Creatinine < 1.5 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier method contraception during and for 3
months after completion of study treatment

- Must be able to tolerate oral intake for the administration of imatinib mesylate and

- No active serious infections

- No known allergy or hypersensitivity to study drugs or their formulation

- No comorbidity or condition which, in the opinion of the investigator, would preclude
study participation

- No other primary malignancy within the past 5 years except basal cell skin cancer,
cervical carcinoma in situ, or another primary malignancy that is not currently
clinically significant or requires active intervention

- No other malignant disease

- No New York Heart Association class III-IV cardiac disease

- No congestive heart failure

- No myocardial infarction within the past 6 months

- No known chronic liver disease (e.g., chronic active hepatitis or cirrhosis)

- No known HIV infection


- See Disease Characteristics

- Prior treatment with gemcitabine hydrochloride, capecitabine, or imatinib mesylate
allowed provided all three drugs were not used in combination simultaneously

- Prior radiotherapy allowed provided the lesion treated is not used to assess response
and has not demonstrated progression after treatment

- At least 2 weeks since prior radiotherapy

- More than 2 weeks since prior major surgery

- At least 4 weeks since prior systemic therapy (6 weeks for nitrosoureas) and

- More than 4 weeks since prior packed red blood cell transfusions

- No prior radiotherapy to ≥ 25% of the bone marrow

- No concurrent anticoagulation therapy with warfarin

- Therapeutic anticoagulation with low-molecular weight heparin or heparin allowed

- Mini-dose warfarin (e.g., 1 mg/day) for prophylaxis of central venous catheter
thrombosis allowed at the discretion of the treating physician

- No other concurrent anticancer agents, including chemotherapy and biologic agents

- No other concurrent investigational drugs

- No concurrent routine systemic corticosteroid therapy (corticosteroid therapy may
only be administered after consultation with the principal investigator)

- Concurrent bisphosphonate therapy allowed for skeletal metastases provided therapy is
started before study entry

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of gemcitabine hydrochloride and capecitabine when combined with imatinib mesylate

Outcome Description:

Cohorts of 3 starting at dose level 0. The imatinib dose is fixed. The dose of capecitabine is initially fixed and the dose of gemcitabine is increased 1 dose level. For the subsequent cohort, the dose of gemcitabine will be fixed and the dose of capecitabine advanced to the next dose level. 3 patients will be treated on the initial schedule. If no dose-limiting toxicities related to drug are observed and no patients require dose mods by the end of cycle 2, then 3 patients will be treated on the next schedule.

Outcome Time Frame:

By the end of cycle 2

Safety Issue:


Principal Investigator

Ralph Hauke, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Nebraska


United States: Federal Government

Study ID:




Start Date:

August 2006

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms



UNMC Eppley Cancer Center at the University of Nebraska Medical Center Omaha, Nebraska  68198-7680