Phase I Study of Imatinib, Gemcitabine and Capecitabine in Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of gemcitabine hydrochloride and capecitabine when combined with imatinib mesylate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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
- •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)
研究组 & 干预措施
Imatinib/Gemcitabine/Capecitabine
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.
干预措施: capecitabine (Drug)
Imatinib/Gemcitabine/Capecitabine
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.
干预措施: gemcitabine hydrochloride (Drug)
Imatinib/Gemcitabine/Capecitabine
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.
干预措施: imatinib mesylate (Drug)
Imatinib/Gemcitabine/Capecitabine
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.
干预措施: mutation analysis (Genetic)
Imatinib/Gemcitabine/Capecitabine
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.
干预措施: nucleic acid sequencing (Genetic)
Imatinib/Gemcitabine/Capecitabine
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.
干预措施: polymerase chain reaction (Genetic)
结局指标
主要结局
Maximum tolerated dose of gemcitabine hydrochloride and capecitabine when combined with imatinib mesylate
时间窗: By the end of cycle 2
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.
Dose-limiting Toxicity
时间窗: By the end of cycle 2.
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.
次要结局
- Antitumor activity(Following response assessment.)