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

NCT00483366 | Completed Phase 1

• 2 other identifiers: 0163-06-FBP30CA036727
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (2)

• 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.

  By the end of cycle 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.

  By the end of cycle 2.

Secondary Outcomes (1)

• Antitumor activity

  Following response assessment.

Study Arms (1)

Imatinib/Gemcitabine/Capecitabine

OTHER

Patients 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.

Drug: capecitabine; Drug: gemcitabine hydrochloride; Drug: imatinib mesylate; Genetic: mutation analysis; Genetic: nucleic acid sequencing; Genetic: polymerase chain reaction

Interventions

capecitabine DRUG

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

Also known as: Xeloda

Imatinib/Gemcitabine/Capecitabine

gemcitabine hydrochloride DRUG

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

Also known as: Gemzar

Imatinib/Gemcitabine/Capecitabine

imatinib mesylate DRUG

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

Also known as: Gleevec

Imatinib/Gemcitabine/Capecitabine

mutation analysis GENETIC

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.

Imatinib/Gemcitabine/Capecitabine

nucleic acid sequencing GENETIC

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.

Imatinib/Gemcitabine/Capecitabine

polymerase chain reaction GENETIC

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.

Imatinib/Gemcitabine/Capecitabine

Eligibility Criteria

• Age: 19 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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:

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Nebraska: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, 68198-6805, United States

Location

MeSH Terms

Interventions

Capecitabine; Gemcitabine; Imatinib Mesylate; Base Sequence; Polymerase Chain Reaction

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena; Nucleic Acid Amplification Techniques; Genetic Techniques; Investigative Techniques

Study Officials

• Ralph Hauke, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

• Elizabeth C. Reed, MD

  University of Nebraska

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2007
• First Posted: June 7, 2007
• Study Start: August 15, 2006
• Primary Completion: January 30, 2009
• Study Completion: March 29, 2011
• Last Updated: September 23, 2024

Record last verified: 2024-09

Locations

US (1)