Safety and Efficacy Study of Gemcitabine Plus Bevacizumab in Patients With Platinum-Resistant Ovarian, Primary Peritoneal or Fallopian Tube Cancer
Primary Purpose
Fallopian Tube Neoplasms, Ovarian Cancer, Primary Peritoneal
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Gemcitabine/Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Fallopian Tube Neoplasms focused on measuring Ovarian Cancer
Eligibility Criteria
Inclusion Criteria:
Patients must have platinum-resistant ovarian, primary peritoneal or fallopian tube cancer.
Patients will be included in the study based on the following criteria:
- Signed informed consent
- Age ≥ 19 yrs
- Advanced, histologically documented ovarian, primary peritoneal, or fallopian tube cancer
- Measurable disease with at least one lesion that can be accurately measured in at least one dimension (longest dimension recorded). Each lesion must be > 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT and MRI, or > 10 mm when measured by spiral CT. OR Clinically or radiologically detectable disease (ascites, peritoneal deposits, mesenteric thickening or lesions that do not fulfill RECIST for measurable disease). In addition, the subject must have two consecutive rising pretreatment CA-125 levels that are both > 2x the institutional upper limit of normal (ULN) and 40.0 IU/ml taken at least 1 week and nor more than 3 months apart.
- Platinum-resistant or refractory cancer; subjects must not have had a biologic or chemotherapeutic regimen for treatment of platinum-resistant disease prior to study entry. Subjects with primary platinum-resistant cancer must have had a tumor recurrence within 6 months after completing or while receiving a platinum-containing regimen. These subjects must not have had any other non-platinum-containing regimen. OR Subjects with secondary platinum-resistant cancer may have had any regimen with any response and then have had tumor recurrence within 6 months after completing or while receiving retreatment with a platinum-containing regimen. These subjects must have received only two prior chemotherapeutic regimens. OR Subjects who receive a chemotherapeutic regimen as consolidation after a response to a platinum-containing regimen must have had tumor recurrence within 6 months after completing or while receiving the consolidation regimen.
- Life expectancy > 12 weeks
- ECOG performance status 0 or 1
- Use of an effective means of contraception (for women of childbearing potential)
- Clinical laboratory test results: Granulocyte count > 1500/µL; Platelet count > 75000/µL; Hemoglobin > 9g/dL (hemoglobin may be supported by transfusion or erythropoietin or other approved hematopoietic growth factors; darbepoetin is permitted); Serum bilirubin < 1.5 the ULN; alkaline phosphatase, AST, and ALT < 2.5 ULN ( AST, ALT < 5.0 ULN for subjects with liver metastasis); Serum creatinine < 1.5 ULN; International normalized ratio (INR) < 1.5 and activated partial thromboplastin time (aPTT) < 1.5 ULN (except for subjects receiving anti-coagulation therapy)
Exclusion Criteria:
- Prior treatment with gemcitabine
- Three or more prior chemotherapeutic regimens for the management of primary disease
- Prior treatment with experimental anti-cancer agents within 4 weeks prior to Day 1 (the day the first study treatment infusions are administered)
- History or clinical evidence of central nervous system or brain metastases
- Prior treatment with Avastin or other anti-angiogenic agent
- Uncontrolled hypercalcemia ( >11.5 mg/dL)
- History of other malignancies within 5 years of Day 1, except for adequately treated carcinoma in situ of the cervix, ductal carcinoma in situ (DCIS) of breast, basal or squamous cell skin cancer
- History of serious systemic disease, unstable angina, myocardial infarction, stroke, transient ischemic attack,, symptoms of CHF, or unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation, paroxysmal supraventricular tachycardia, are eligible) within 6 months prior to Day 1 of treatment
- Known HIV infection
- Pregnancy or lactation
- Major surgery, open biopsy, or significant traumatic injury within 4 weeks prior to Day 1 of treatment, or anticipation of need for major surgical procedure during the course of the study
- Inability to comply with study and follow-up procedures
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications
- Life expectancy of less than 12 weeks
- Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
- Any prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
- Known CNS disease
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
- Symptomatic peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Any patient that the clinician considers at risk for possible GI perforation. This includes patients with clinical symptoms or signs of GI obstruction or who require parenteral nutrition, parenteral hydration, or tube feeding, and patients with evidence of free air not explained by paracentesis or recent surgical procedure.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
- Serious, non-healing wound, ulcer, or bone fracture
- Proteinuria at screening as demonstrated by either Urine protein:creatinine (UPC) ratio ≥ 1.0 at screening OR Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
- Known hypersensitivity to any component of bevacizumab
- Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single
Arm Description
Outcomes
Primary Outcome Measures
Progression-free survival
The primary outcome measure is progression-free survival. Disease status and response rates will be determined by investigator assessment using RECIST or CA-125 changes (subjects with nonmeasurable disease only)
Secondary Outcome Measures
Safety and tolerability of bevacizumab in combination with gemcitabine will be assessed.
The safety and tolerability of bevacizumab in combination with gemcitabine will be assessed using the following measures:
- Incidence, nature, severity, and relatedness of adverse events graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE, Version 3.0)
Full Information
NCT ID
NCT01131039
First Posted
May 21, 2010
Last Updated
December 19, 2013
Sponsor
Emory University
Collaborators
Genentech, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01131039
Brief Title
Safety and Efficacy Study of Gemcitabine Plus Bevacizumab in Patients With Platinum-Resistant Ovarian, Primary Peritoneal or Fallopian Tube Cancer
Official Title
A Phase II Trial of Gemcitabine Plus Bevacizumab in Patients With Platinum-Resistant Ovarian, Primary Peritoneal or Fallopian Tube Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
December 2013
Overall Recruitment Status
Withdrawn
Why Stopped
PI left Emory
Study Start Date
January 2011 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Emory University
Collaborators
Genentech, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to determine whether the administration of bevacizumab and gemcitabine given by IV infusion can prolong survival, delay tumor growth, and/or shrink tumors in patients with ovarian cancer, primary peritoneal, or fallopian tube cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fallopian Tube Neoplasms, Ovarian Cancer, Primary Peritoneal
Keywords
Ovarian Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Gemcitabine/Bevacizumab
Other Intervention Name(s)
Gemcitabine, Gemzar®, Bevacizumab, Avastin
Intervention Description
Gemcitabine: IV, days 1,8, and every 21 days
Bevacizumab: IV, day 1 and every 21 days until disease progression
Primary Outcome Measure Information:
Title
Progression-free survival
Description
The primary outcome measure is progression-free survival. Disease status and response rates will be determined by investigator assessment using RECIST or CA-125 changes (subjects with nonmeasurable disease only)
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Safety and tolerability of bevacizumab in combination with gemcitabine will be assessed.
Description
The safety and tolerability of bevacizumab in combination with gemcitabine will be assessed using the following measures:
- Incidence, nature, severity, and relatedness of adverse events graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE, Version 3.0)
Time Frame
2 years
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must have platinum-resistant ovarian, primary peritoneal or fallopian tube cancer.
Patients will be included in the study based on the following criteria:
Signed informed consent
Age ≥ 19 yrs
Advanced, histologically documented ovarian, primary peritoneal, or fallopian tube cancer
Measurable disease with at least one lesion that can be accurately measured in at least one dimension (longest dimension recorded). Each lesion must be > 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT and MRI, or > 10 mm when measured by spiral CT. OR Clinically or radiologically detectable disease (ascites, peritoneal deposits, mesenteric thickening or lesions that do not fulfill RECIST for measurable disease). In addition, the subject must have two consecutive rising pretreatment CA-125 levels that are both > 2x the institutional upper limit of normal (ULN) and 40.0 IU/ml taken at least 1 week and nor more than 3 months apart.
Platinum-resistant or refractory cancer; subjects must not have had a biologic or chemotherapeutic regimen for treatment of platinum-resistant disease prior to study entry. Subjects with primary platinum-resistant cancer must have had a tumor recurrence within 6 months after completing or while receiving a platinum-containing regimen. These subjects must not have had any other non-platinum-containing regimen. OR Subjects with secondary platinum-resistant cancer may have had any regimen with any response and then have had tumor recurrence within 6 months after completing or while receiving retreatment with a platinum-containing regimen. These subjects must have received only two prior chemotherapeutic regimens. OR Subjects who receive a chemotherapeutic regimen as consolidation after a response to a platinum-containing regimen must have had tumor recurrence within 6 months after completing or while receiving the consolidation regimen.
Life expectancy > 12 weeks
ECOG performance status 0 or 1
Use of an effective means of contraception (for women of childbearing potential)
Clinical laboratory test results: Granulocyte count > 1500/µL; Platelet count > 75000/µL; Hemoglobin > 9g/dL (hemoglobin may be supported by transfusion or erythropoietin or other approved hematopoietic growth factors; darbepoetin is permitted); Serum bilirubin < 1.5 the ULN; alkaline phosphatase, AST, and ALT < 2.5 ULN ( AST, ALT < 5.0 ULN for subjects with liver metastasis); Serum creatinine < 1.5 ULN; International normalized ratio (INR) < 1.5 and activated partial thromboplastin time (aPTT) < 1.5 ULN (except for subjects receiving anti-coagulation therapy)
Exclusion Criteria:
Prior treatment with gemcitabine
Three or more prior chemotherapeutic regimens for the management of primary disease
Prior treatment with experimental anti-cancer agents within 4 weeks prior to Day 1 (the day the first study treatment infusions are administered)
History or clinical evidence of central nervous system or brain metastases
Prior treatment with Avastin or other anti-angiogenic agent
Uncontrolled hypercalcemia ( >11.5 mg/dL)
History of other malignancies within 5 years of Day 1, except for adequately treated carcinoma in situ of the cervix, ductal carcinoma in situ (DCIS) of breast, basal or squamous cell skin cancer
History of serious systemic disease, unstable angina, myocardial infarction, stroke, transient ischemic attack,, symptoms of CHF, or unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation, paroxysmal supraventricular tachycardia, are eligible) within 6 months prior to Day 1 of treatment
Known HIV infection
Pregnancy or lactation
Major surgery, open biopsy, or significant traumatic injury within 4 weeks prior to Day 1 of treatment, or anticipation of need for major surgical procedure during the course of the study
Inability to comply with study and follow-up procedures
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications
Life expectancy of less than 12 weeks
Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
Any prior history of hypertensive crisis or hypertensive encephalopathy
New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
Known CNS disease
Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
Symptomatic peripheral vascular disease
Evidence of bleeding diathesis or coagulopathy
Any patient that the clinician considers at risk for possible GI perforation. This includes patients with clinical symptoms or signs of GI obstruction or who require parenteral nutrition, parenteral hydration, or tube feeding, and patients with evidence of free air not explained by paracentesis or recent surgical procedure.
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
Serious, non-healing wound, ulcer, or bone fracture
Proteinuria at screening as demonstrated by either Urine protein:creatinine (UPC) ratio ≥ 1.0 at screening OR Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
Known hypersensitivity to any component of bevacizumab
Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sharmila Makhija, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy Study of Gemcitabine Plus Bevacizumab in Patients With Platinum-Resistant Ovarian, Primary Peritoneal or Fallopian Tube Cancer
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