A Phase I/II Trial of Weekly Paclitaxel In Combination With Ganetespib In Patients With Recurrent, Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Response Rate Defined as the Proportion of Patients With a Best Response of Complete Response (CR) or Partial Response (PR) Per RECIST v. 1.1 (Phase II)
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of ganetespib when given together with paclitaxel and to see how well they work in treating patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Ganetespib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving paclitaxel and ganetespib may be an effective treatment for ovarian, fallopian tube, or primary peritoneal cancer.
详细描述
PRIMARY OBJECTIVES:
I. Determine the recommended Phase II dose of ganetespib with weekly paclitaxel. (Phase I) II. Probability of surviving progression-free for at least 6 months after initiating therapy. (Phase II) III. Clinical response rate (partial and complete responses as defined by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria). (Phase II)
SECONDARY OBJECTIVES:
I. Determine the nature and degree of toxicity of ganetespib and weekly paclitaxel in this cohort of patients as measured by the frequency and severity of adverse reactions. (Phase I) II. Determine the nature and degree of toxicity of ganetespib and weekly paclitaxel in this cohort of patients as measured by the frequency and severity of adverse reactions encountered. (Phase II) III. Duration of progression-free survival. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of ganetespib followed by a phase II study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically or cytologically confirmed recurrent epithelial ovarian, fallopian tube or primary peritoneal cancers who have received up to two prior treatment regimens
- •Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria version (v.) 1.1
- •Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation, or extended therapy administered after completion of initial chemotherapy; patients must be considered platinum resistant or refractory according to standard Gynecologic Oncology Group (GOG) criteria, i.e., have had a treatment-free interval following platinum of less than 12 months, have persistent disease at the completion of primary platinum-based therapy or have progressed during platinum-based therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 -2
- •Leukocytes >= 3,000/mcL
- •Absolute neutrophil count >= 1,500/mcL
- •Platelets >= 100,000/mcL
- •Total bilirubin =< normal institutional limits
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) (serum glutamic oxaloacetic transaminase [SGOT]/serum glutamate pyruvate transaminase [SGPT]) =< 2 times institutional normal limits
- •Creatinine =< normal institutional limits OR
- •Creatinine clearance >= 60 Ml/min/1.73 m^2 for patients with creatinine levels above institutional normal
- •Ability and willingness to comply with scheduled visits, treatment plan, laboratory assessments and other study procedures
- •Ability to understand and willingness to sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) consent document
排除标准
- •Patients who have had surgery, chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have toxicity that has not recovered to =< grade 1 from adverse events due to agents administered more than 4 weeks earlier (with the exception of alopecia); patients may not be receiving any other investigational agents
- •Histologic diagnosis of a benign or borderline tumor ('tumor of low malignant potential') or of a malignant tumor of non-epithelial origin (such as a germ cell tumor, sex-cord stromal tumor) of the ovary, fallopian tube or peritoneum
- •Patients with known brain metastases
- •History of allergic reactions to Cremophor EL, paclitaxel or its components
- •Prior history of >= grade 2 neurotoxicity or any other toxicity requiring discontinuation of taxane therapy that has not resolved to =< grade 1, with the exception of alopecia
- •Diagnosis of another malignancy within two years before the first dose, or previously treated for another malignancy with evidence of residual disease, with the exception of a synchronous endometrial cancer; carcinoma in situ will not be considered as malignancy
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, known serious cardiac illness or psychiatric illness/social situations that would limit compliance with study requirements; known serious cardiac illness or medical conditions include, but are not limited to:
- •History of documented congestive heart failure (CHF), New York Heart Association (NYHA) class II/III/IV, with a history of dyspnea, orthopnea, or edema that requires current treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, beta blockers, or diuretics
- •NOTE: use of these medications for the treatment of hypertension is allowed
- •Screening QTc (QT interval corrected for heart rate) > 470 msec or history of QT (cardiac interval from start of Q wave to end of T wave) prolongation while taking other medications
- •High-risk uncontrolled arrhythmias (ventricular arrhythmias, high-grade atrioventricular [AV]-block, supra-ventricular arrhythmias that are not adequately rate-controlled)
- •Arrhythmias that require current treatment with the following anti-arrhythmic drugs: flecainide, moricizine, or propafenone
- •Current coronary artery disease with a history of myocardial infarction, angioplasty, or coronary bypass surgery within the preceding 6 months, or angina pectoris that has been symptomatic within the preceding 6 months
- •Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- •Pregnant or breast feeding
研究组 & 干预措施
Phase 1: 100 mg/m2 ganetespib, 80 mg/m2 paclitaxel
Patients receive paclitaxel IV over 1 hour and ganetespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Ganetespib escalation will follow a modified 3+3 design and escalate from 100mg/m2 to 125mg/m2 to 150mg/m2.
干预措施: paclitaxel (Drug)
Phase 1: 100 mg/m2 ganetespib, 80 mg/m2 paclitaxel
Patients receive paclitaxel IV over 1 hour and ganetespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Ganetespib escalation will follow a modified 3+3 design and escalate from 100mg/m2 to 125mg/m2 to 150mg/m2.
干预措施: ganetespib (Drug)
Phase 1: 100 mg/m2 ganetespib, 80 mg/m2 paclitaxel
Patients receive paclitaxel IV over 1 hour and ganetespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Ganetespib escalation will follow a modified 3+3 design and escalate from 100mg/m2 to 125mg/m2 to 150mg/m2.
干预措施: laboratory biomarker analysis (Other)
Phase I: 125 mg/m2 ganetespib, 80 mg/m2 paclitaxel
Patients receive paclitaxel IV over 1 hour and ganetespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Ganetespib escalation will follow a modified 3+3 design and escalate from 100mg/m2 to 125mg/m2 to 150mg/m2.
干预措施: paclitaxel (Drug)
Phase I: 125 mg/m2 ganetespib, 80 mg/m2 paclitaxel
Patients receive paclitaxel IV over 1 hour and ganetespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Ganetespib escalation will follow a modified 3+3 design and escalate from 100mg/m2 to 125mg/m2 to 150mg/m2.
干预措施: ganetespib (Drug)
Phase I: 125 mg/m2 ganetespib, 80 mg/m2 paclitaxel
Patients receive paclitaxel IV over 1 hour and ganetespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Ganetespib escalation will follow a modified 3+3 design and escalate from 100mg/m2 to 125mg/m2 to 150mg/m2.
干预措施: laboratory biomarker analysis (Other)
Phase I: 150 mg/m2 ganetespib, 80 mg/m2 paclitaxel
Patients receive paclitaxel IV over 1 hour and ganetespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Ganetespib escalation will follow a modified 3+3 design and escalate from 100mg/m2 to 125mg/m2 to 150mg/m2.
干预措施: paclitaxel (Drug)
Phase I: 150 mg/m2 ganetespib, 80 mg/m2 paclitaxel
Patients receive paclitaxel IV over 1 hour and ganetespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Ganetespib escalation will follow a modified 3+3 design and escalate from 100mg/m2 to 125mg/m2 to 150mg/m2.
干预措施: ganetespib (Drug)
Phase I: 150 mg/m2 ganetespib, 80 mg/m2 paclitaxel
Patients receive paclitaxel IV over 1 hour and ganetespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Ganetespib escalation will follow a modified 3+3 design and escalate from 100mg/m2 to 125mg/m2 to 150mg/m2.
干预措施: laboratory biomarker analysis (Other)
Phase II: MTD/MED of ganetespib, 80 mg/m2 paclitaxel
Paclitaxel IV given over 1 hour at 80 mg/m2 days 1, 8 and 15 of a 28-day cycle. PLUS ganetespib IV at MTD/MED from Phase I on days 1, 8 and 15 of a 28-day cycle.
干预措施: paclitaxel (Drug)
Phase II: MTD/MED of ganetespib, 80 mg/m2 paclitaxel
Paclitaxel IV given over 1 hour at 80 mg/m2 days 1, 8 and 15 of a 28-day cycle. PLUS ganetespib IV at MTD/MED from Phase I on days 1, 8 and 15 of a 28-day cycle.
干预措施: ganetespib (Drug)
Phase II: MTD/MED of ganetespib, 80 mg/m2 paclitaxel
Paclitaxel IV given over 1 hour at 80 mg/m2 days 1, 8 and 15 of a 28-day cycle. PLUS ganetespib IV at MTD/MED from Phase I on days 1, 8 and 15 of a 28-day cycle.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Response Rate Defined as the Proportion of Patients With a Best Response of Complete Response (CR) or Partial Response (PR) Per RECIST v. 1.1 (Phase II)
时间窗: Up to 4 years
Recommended Phase II Dose of Ganetespib With Weekly Paclitaxel, Based on the Incidence of Dose-limiting Toxicity (DLT) Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 (Phase I)
时间窗: Up to 28 days
Progression-free Survival at 6 Months (Phase II)
时间窗: From start of treatment to time of progression or death, whichever occurs first, assessed at 6 months
次要结局
- Duration of Progression-free Survival (Phase II)(From start of treatment to time of progression or death, whichever occurs first, assessed up to 4 years)