Chemotherapy in Treating Patients With Refractory Advanced Solid Tumors or Hematologic Cancer
A Phase I Trial of 17-N-Allylamino-17-Demethoxy Geldanamycin (17-AAG, NSC #330507) Daily X 5 in Patients With Advanced Cancer Therapeutic Protocol
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin in treating patients with refractory advanced solid tumors or hematologic cancers.
研究概览
详细说明
OBJECTIVES:
- Determine the maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) in patients with refractory or advanced solid tumors or hematologic malignancies.
- Evaluate the effects of this drug on the expression of signaling proteins present on an individual patient's cancer at the start of treatment and, if possible, post treatment.
OUTLINE: This is a two-phase, dose-escalation, multicenter study. Patients are stratified according to disease (chronic myelogenous leukemia [CML] or Philadelphia chromosome [Ph]+ acute lymphoblastic leukemia [ALL] vs solid tumor).
Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 60-90 minutes twice weekly. Courses repeat every 12 weeks in the absence of disease progression (after at least 2 courses for CML or Ph+ ALL patients) or unacceptable toxicity.
- Accelerated phase: Single patients receive escalating dose levels of 17-AAG until one patient experiences a first course grade 3 or greater toxicity or two different patients experience grade 2 toxicity during any course.
- Standard phase: Cohorts of 3-6 patients in each stratum receive escalating doses of 17-AAG 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.
PROJECTED ACCRUAL: Approximately 51 patients will be accrued for this study.
研究类型
阶段
- 阶段1
联系人和位置
学习地点
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California
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Los Angeles、California、美国、90095
- Jonsson Comprehensive Cancer Center, UCLA
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New York
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New York、New York、美国、10021
- Memorial Sloan-Kettering Cancer Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
DISEASE CHARACTERISTICS:
Diagnosis of 1 of the following:
Histologically confirmed advanced primary or malignant solid tumor refractory to standard therapy or for which no curative standard therapy exists
Progressive disease evidenced by 1 of the following:
Non-prostate cancer (including, but not limited to, breast, ovary, head and neck, non-small cell lung, bladder, kidney, colon, stomach, or malignant melanoma)
- Development of new lesions or an increase in existing lesions
- No increase in a biochemical marker (e.g., carcinoembryonic antigen, CA-15-3, or an increase in symptoms) as sole measure of disease
Prostate cancer (androgen independent) meeting the following criteria:
- Progressing metastatic disease on bone scan, CT scan, or MRI
Metastatic disease and rising prostate-specific antigen (PSA) values meeting 1 of the following criteria:
- At least 3 rising PSA values obtained at least 1 week apart = 2 rising values more than 1 month apart with at least 25% increase over the range of values
- Serum testosterone less than 30 ng/mL
- Castrate status should be maintained by medical therapies if orchiectomy has not been performed
- Progressive disease must be evident off antiandrogen therapy if received prior to study entry
- Registered to protocol MSKCC-9040
Cytologically confirmed chronic, accelerated, or blastic phase chronic myelogenous leukemia (CML) or Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) refractory to standard therapy or for which no curative therapy exists
Progressive disease evidenced by 1 of the following:
- Accelerated or blastic phase disease that is not responsive to standard therapy or loss of hematologic response to imatinib mesylate while remaining in chronic phase for CML
- Relapsed or refractory after treatment with standard chemotherapy and imatinib mesylate for Ph-positive ALL
- No active CNS or epidural tumor
Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Sex:
- Not specified
Menopausal status:
- Not specified
Performance status:
- Karnofsky 70-100%
Life expectancy:
- At least 6 months
Hematopoietic:
- WBC greater than 3,500/mm^3
- Platelet count greater than 100,000/mm^3
- No restrictions based on peripheral blood counts for CML and Ph-positive ALL
Hepatic:
- Bilirubin no greater than 1.2 times upper limit of normal (ULN)
- AST less than 1.5 times ULN
- Prothrombin time normal
Renal:
- Creatinine no greater than 1.5 times ULN OR
- Creatinine clearance greater than 60 mL/min
Cardiovascular:
- No myocardial infarction within the past 6 months
- Ejection fraction greater than 45% by radionuclide cardiac angiography
- No ventricular aneurysm or other abnormal wall motion
No reversible defect by thallium stress test if any of the following conditions are present:
- Ejection fraction less than 45% on radionuclide angiocardiography
- Worrisome but nonexclusive cardiovascular history
- Abnormal echocardiogram
Patients with the following history or clinical findings require additional diagnostic testing:
- Significant Q waves (greater than 3 mm or greater than one-third of the height of the QRS complex)
- ST elevation or depressions of greater than 2 mm that are not attributable to hypertension strain
- Absence of regular sinus rhythm
- Bundle branch block
- Requirement for diuretics for reasons other than hypertension or digoxin for reasons other than atrial fibrillation
- Prior mild to moderate congestive heart failure
- No New York Heart Association class III or IV heart disease
- No angina pectoris
- No uncontrolled hypertension or intermittent claudication
- No severe debilitating valvular disease
Pulmonary:
- No severe debilitating pulmonary disease
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active infection requiring IV antibiotics
- No symptomatic peripheral neuropathy grade 2 or higher
- No other severe medical conditions that would increase risk for toxicity
- No allergy to eggs or egg products
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 4 weeks since prior biologic therapy (including interferon for CML) and recovered
Chemotherapy:
- At least 4 weeks since prior chemotherapy (3 days for hydroxyurea for CML or ALL) and recovered
- No other concurrent chemotherapy
Endocrine therapy:
- See Disease Characteristics
- At least 4 weeks since prior endocrine therapy and recovered
Radiotherapy:
- At least 4 weeks since prior radiotherapy and recovered
- Concurrent radiotherapy to localized disease sites not being used to evaluate antitumor response allowed
- No concurrent radiotherapy to only measurable lesion
Surgery:
- See Disease Characteristics
- Prior orchiectomy allowed
- No concurrent surgery
Other:
- At least 3 days since prior imatinib mesylate for CML or ALL
- At least 4 weeks since prior investigational anticancer drugs and recovered
- At least 4 weeks since prior palliative treatment for metastatic disease
- No concurrent ketoconazole, warfarin, verapamil, miconazole, or erythromycin
- No other concurrent investigational drugs
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
合作者和调查者
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
- IV期肾细胞癌
- 复发性肾细胞癌
- IV期乳腺癌
- IIIA期乳腺癌
- 复发性乳腺癌
- IIIB期乳腺癌
- 复发性非小细胞肺癌
- III期膀胱癌
- 复发性膀胱癌
- IV期膀胱癌
- III期前列腺癌
- IV期前列腺癌
- 复发性前列腺癌
- IIIA期非小细胞肺癌
- IIIB期非小细胞肺癌
- IV期非小细胞肺癌
- 未指定的成人实体瘤,具体方案
- 未经治疗的转移性鳞状颈癌伴隐匿原发性
- 复发性转移性鳞状颈部癌伴隐匿性原发灶
- III期唇和口腔鳞状细胞癌
- III期唇基底细胞癌
- III期口腔疣状癌
- III期口腔粘液表皮样癌
- III期口腔腺样囊性癌
- IV期唇和口腔鳞状细胞癌
- IV期唇基底细胞癌
- IV期口腔疣状癌
- IV期口腔粘液表皮样癌
- IV期口腔腺样囊性癌
- 唇和口腔复发性鳞状细胞癌
- 唇部复发性基底细胞癌
- 复发性口腔疣状癌
- 复发性口腔黏液表皮样癌
- 复发性口腔腺样囊性癌
- III期口咽鳞状细胞癌
- III期口咽淋巴上皮瘤
- IV期口咽鳞状细胞癌
- IV期口咽淋巴上皮瘤
- 复发性口咽鳞状细胞癌
- 复发性口咽淋巴上皮瘤
- III期鼻咽鳞状细胞癌
- III期鼻咽淋巴上皮瘤
- IV期鼻咽鳞状细胞癌
- IV期鼻咽淋巴上皮瘤
- 复发性鼻咽鳞状细胞癌
- 复发性鼻咽淋巴上皮瘤
- 下咽部 III 期鳞状细胞癌
- 下咽部鳞状细胞癌 IV 期
- 下咽部复发性鳞状细胞癌
- III期喉鳞状细胞癌
- III期喉疣状癌
- IV期喉鳞状细胞癌
- IV期喉疣状癌
- 复发性喉癌
- 复发性喉癌
- III期鼻窦和鼻腔鳞状细胞癌
- III 期鼻窦和鼻腔中线致死性肉芽肿
- III期鼻窦和鼻腔感觉神经母细胞瘤
- IV 期鼻窦和鼻腔鳞状细胞癌
- IV 期鼻窦和鼻腔中线致死性肉芽肿
- IV 期鼻窦和鼻腔感觉神经母细胞瘤
- 鼻窦和鼻腔复发性鳞状细胞癌
- 鼻窦和鼻腔复发性中线致死性肉芽肿
- 鼻窦鼻腔复发性感觉神经母细胞瘤
- 复发性唾液腺癌
- III期唾液腺癌
- Ⅳ期唾液腺癌
- IV期结肠癌
- 复发性结肠癌
- III期卵巢上皮癌
- IV期卵巢上皮癌
- 复发性卵巢上皮癌
- III期结肠癌
- IIIC期乳腺癌
- 复发性黑色素瘤
- IV期黑色素瘤
- 慢性期慢性粒细胞白血病
- 母细胞期慢性粒细胞白血病
- 复发性慢性粒细胞白血病
- IV期胃癌
- 胃癌复发
- III期肾细胞癌
- III期黑色素瘤
- III期胃癌
- 复发性成人急性淋巴细胞白血病
- 卵巢肉瘤
- 加速期慢性粒细胞白血病
- 交界性卵巢表面上皮间质瘤
- 卵巢间质癌
- 复发性卵巢生殖细胞瘤
- III期卵巢生殖细胞瘤
- IV期卵巢生殖细胞瘤
- 鼻窦鼻腔复发性内翻性乳头状瘤
- 鼻窦鼻腔内翻性乳头状瘤Ⅲ期
- IV期鼻窦鼻腔内翻性乳头状瘤
其他相关的 MeSH 术语
其他研究编号
- 99-037
- CDR0000067267 (注册表标识符:PDQ (Physician Data Query))
- NCI-T99-0035
- UCLA-0206019
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