Paclitaxel and Ganetespib in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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. Patients receive paclitaxel intravenously (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. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Official Title
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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

Conditions
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Recurrent Fallopian Tube Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer

Intervention / Treatment
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* Drug: paclitaxel
* Drug: ganetespib
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Phase I Treatment: Paclitaxel IV given over 1 hour at 80 mg/m2 days 1, 8 and 15 of a 28-day cycle. PLUS ganetespib IV at a starting dose of 100 mg/m2 on days 1, 8 and 15 of a 28-day cycle. Ganetespib escalation will follow a modified 3+3 design and escalate from 100mg/m2 to 125mg/m2 to 150mg/m2. Phase II Treatment: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: 100 mg/m2 ganetespib, 80 mg/m2 paclitaxel<br>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. | Drug: paclitaxel<br>* Given IV<br>* Other names: Taxol;Drug: ganetespib<br>* Given IV<br>* Other names: STA-9090;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Phase I: 125 mg/m2 ganetespib, 80 mg/m2 paclitaxel<br>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. | Drug: paclitaxel<br>* Given IV<br>* Other names: Taxol;Drug: ganetespib<br>* Given IV<br>* Other names: STA-9090;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Phase I: 150 mg/m2 ganetespib, 80 mg/m2 paclitaxel<br>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. | Drug: paclitaxel<br>* Given IV<br>* Other names: Taxol;Drug: ganetespib<br>* Given IV<br>* Other names: STA-9090;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Phase II: MTD/MED of ganetespib, 80 mg/m2 paclitaxel<br>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. | Drug: paclitaxel<br>* Given IV<br>* Other names: Taxol;Drug: ganetespib<br>* Given IV<br>* Other names: STA-9090;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) |  | Up to 28 days | 
| Progression-free Survival at 6 Months (Phase II) |  | From start of treatment to time of progression or death, whichever occurs first, assessed at 6 months | 
| 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) |  | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |