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Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00483366

Imatinib Mesylate, Gemcitabine, and Capecitabine in Treating Patients With Advanced Solid Tumors

A Phase 1 study testing capecitabine, gemcitabine hydrochloride and imatinib mesylate in people with Unspecified Adult Solid Tumor, Protocol Specific, run by University of Nebraska at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages 19 to 120 years
What is being tested?
capecitabine, gemcitabine hydrochloride and imatinib mesylate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
15 Aug 2006to 29 Mar 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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:
  • Leptomeningeal disease
  • Bone lesions
  • 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 steroids
  • 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 syndrome)
  • AST and ALT ≤ 2.5 times ULN
  • Creatinine < 1.5 times ULN
  • 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 capecitabine
  • 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 recovered
  • More than 4 weeks since prior packed red blood cell transfusions
  • Concurrent bisphosphonate therapy allowed for skeletal metastases provided therapy is started before study entry

Who cannot join

  • Not pregnant or nursing/negative pregnancy test
  • No active serious infections
  • No known allergy or hypersensitivity to study drugs or their formulation
  • No comorbidity or condition which 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 prior radiotherapy to ≥ 25% of the bone marrow
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  • 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)
  • 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
  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site
  • UNMC Eppley Cancer Center at the University of Nebraska Medical Center

    Omaha, Nebraska, 68198-6805

Other trials in United States

About this study

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

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

PURPOSE: This phase I trial is studying the side effects and best dose of gemcitabine and capecitabine when given together with imatinib mesylate in treating patients with advanced solid tumors.

Read the detailed description

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

Being tested
capecitabine, gemcitabine hydrochloride, imatinib mesylate, mutation analysis, nucleic acid sequencing
Keywords
unspecified adult solid tumor, protocol specific

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • capecitabineDrug

    Also called Xeloda

    Dose level Capecitabine

    -1 400 mg/m2 bid

    0 500 mg/m2 bid

    1. 500 mg/m2 bid
    2. 600 mg/m2 bid
    3. 600 mg/m2 bid
    4. 725 mg/m2 bid
    5. 725 mg/m2 bid
    6. 850 mg/m2 bid
    7. 850 mg/m2 bid
  • gemcitabine hydrochlorideDrug

    Also called Gemzar

    Dose level Gemcitabine

    -1 400 mg/m2 0 450 mg/m2

    1. 550 mg/m2
    2. 550 mg/m2
    3. 675 mg/m2
    4. 675 mg/m2
    5. 825 mg/m2
    6. 825 mg/m2
    7. 1000 mg/m2
  • imatinib mesylateDrug

    Also called Gleevec

    Dose level Imatinib

    -1 400 mg/d 0 400 mg/d

    1. 400 mg/d
    2. 400 mg/d
    3. 400 mg/d
    4. 400 mg/d
    5. 400 mg/d
    6. 400 mg/d
    7. 400 mg/d
  • mutation analysisGenetic

    C-kit mutations will be assessed on existing paraffin-embedded blocks by Polymerase Chain Reaction and direct sequencing of both juxtamembrane domains (exons 9 and 11) and the tyrosine kinase domain (exons 13 and 17). Every ABI sequence will be compared to a NCBI Human KIT gene nucleotide sequence and will be blast using a NCBI Standard Nucleotide Blast Search to determine the presence of mutation within a particular exon.

  • nucleic acid sequencingGenetic

    C-kit mutations will be assessed on existing paraffin-embedded blocks by Polymerase Chain Reaction and direct sequencing of both juxtamembrane domains (exons 9 and 11) and the tyrosine kinase domain (exons 13 and 17). Every ABI sequence will be compared to a NCBI Human KIT gene nucleotide sequence and will be blast using a NCBI Standard Nucleotide Blast Search to determine the presence of mutation within a particular exon.

  • polymerase chain reactionGenetic

    C-kit mutations will be assessed on existing paraffin-embedded blocks by Polymerase Chain Reaction and direct sequencing of both juxtamembrane domains (exons 9 and 11) and the tyrosine kinase domain (exons 13 and 17). Every ABI sequence will be compared to a NCBI Human KIT gene nucleotide sequence and will be blast using a NCBI Standard Nucleotide Blast Search to determine the presence of mutation within a particular exon.

Study groups in NCT00483366
Study groupRoleWhat they receive
Imatinib/Gemcitabine/CapecitabineOtherPatients will be accrued on cohorts of three per dose level starting at dose level 0. Accrual to higher dose levels will depend on toxicity occurrence. Dose limiting toxicity (DLT) will be determined after cycle two for each patient. Schema: Imatinib days 1 - 5 and days 8 - 12 Gemcitabine on days 3 and 10 Capecitabine on days 1 - 14 Doses: Imatinib 400 mg/d fixed dose Gemcitabine 450 mg/m2; 550 mg/m2; 675 mg/m2; 825 mg/m2; 1000 mg/m2 Capecitabine 500 mg/m2; 600 mg/m2 bid; 725 mg/m2; 850 mg/m2 Treatment cycle: 21-days Treatment duration: Until disease progression or unacceptable toxicity defined in protocol.
Receives: Drug: capecitabine; Drug: gemcitabine hydrochloride; Drug: imatinib mesylate; Genetic: mutation analysis; Genetic: nucleic acid sequencing; Genetic: polymerase chain reaction

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

    Measured: By the end of cycle 2

  2. Dose-limiting Toxicity

    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.

    Measured: By the end of cycle 2.

Secondary outcomes (1)
  1. Antitumor activity

    Deidentified melanoma samples will be sent to our collaborator at Ohio State, Dr. Christopher Corless, who is a recognized expert in this field. Renal cell samples will be assayed here at our institution

    Measured: Following response assessment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2007 (estimated)
  2. Study start15 Aug 2006
  3. Primary completion30 Jan 2009
  4. Study completion29 Mar 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00483366
Sponsor's protocol ID
0163-06-FB
Other IDs
P30CA036727
Status last verified
Sep 2024
First submitted
6 Jun 2007
Last updated
23 Sep 2024
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing capecitabine, gemcitabine hydrochloride and imatinib mesylate in people with Unspecified Adult Solid Tumor, Protocol Specific, run by University of Nebraska at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose of gemcitabine hydrochloride and capecitabine when combined with imatinib mesylate (time frame: By the end of cycle 2). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2024.

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