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

Phase 1

Terminated

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

Interventions: Drug: paclitaxel
Drug: ganetespib
Other: laboratory biomarker analysis

Registration Number: NCT01962948

Lead Sponsor: Fox Chase Cancer Center

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 12

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase I: 125 mg/m2 ganetespib, 80 mg/m2 paclitaxel	ganetespib	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.
Phase I: 150 mg/m2 ganetespib, 80 mg/m2 paclitaxel	ganetespib	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.
Phase II: MTD/MED of ganetespib, 80 mg/m2 paclitaxel	ganetespib	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.
Phase 1: 100 mg/m2 ganetespib, 80 mg/m2 paclitaxel	laboratory biomarker analysis	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.
Phase I: 125 mg/m2 ganetespib, 80 mg/m2 paclitaxel	laboratory biomarker analysis	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.
Phase II: MTD/MED of ganetespib, 80 mg/m2 paclitaxel	laboratory biomarker analysis	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.
Phase I: 150 mg/m2 ganetespib, 80 mg/m2 paclitaxel	laboratory biomarker analysis	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.
Phase 1: 100 mg/m2 ganetespib, 80 mg/m2 paclitaxel	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.
Phase 1: 100 mg/m2 ganetespib, 80 mg/m2 paclitaxel	ganetespib	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.
Phase I: 125 mg/m2 ganetespib, 80 mg/m2 paclitaxel	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.
Phase I: 150 mg/m2 ganetespib, 80 mg/m2 paclitaxel	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.
Phase II: MTD/MED of ganetespib, 80 mg/m2 paclitaxel	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.

Primary Outcome Measures

Name	Time	Method
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
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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (2): Abramson Cancer Center of the University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States