Fallopian Tube Cancer, Malignant Tumor of Peritoneum, Ovarian Cancer
Conditions
Keywords
recurrent ovarian epithelial cancer, recurrent primary peritoneal cavity cancer, recurrent fallopian tube cancer
Brief summary
The purpose of this study is to evaluate the effectiveness of the combination of Avastin and Docetaxel in the treatment of women with platinum sensitive recurrent epithelial ovarian cancer within 12 months of platinum chemotherapy.
Interventions
DRUGAvastin
Day 1, every 21 day cycle
DRUGDocetaxel
Day 1, 8, every 21 day cycle
Sponsors
National Cancer Institute (NCI)
Genentech, Inc.
Sanofi
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent * Pathologically confirmed epithelial ovarian cancer, peritoneal serous cancer, or fallopian tube cancer * Patient's disease recurrence or progression occurs between 0 to 12 months (1 to 365 days) from prior platinum-containing chemotherapy regimen. Patients, however, may not receive study drug until at least 28 days from prior chemotherapy. * The patient may have received up to three prior chemotherapy regimens for the treatment of this malignancy. Patients who may have received prior treatment with paclitaxel and/or a platinum compound will be allowed. Rechallenge with the same platinum based regimen is considered 1 prior regimen. Patients who have been treated with consolidation treatment are allowed and the consolidation will not be considered a separate regimen. Hormonal therapy (i.e. progesterones, estrogens, anti-estrogens, aromatase inhibitors) will not be considered a prior chemotherapy regimen. * Measurable or evaluable disease either by the Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) or cancer antigen (CA)125 criteria \[Journal of the National Cancer Institute (JNCI), Vol. 96, No. 6, March 17, 2004, Vergote JNCI 2000\] * At least 4 weeks since major surgery, with full recovery * At least 3 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside of the radiation port. * Eastern Cooperative Oncology Group (ECOG) performance status \</= 2 * Hematologic (minimal values): Absolute neutrophil count \>/= 1,500/mm\^3, Hemoglobin \>/= 8.0 g/dL (transfusions allowed), Platelet count \>/= 100,000/mm\^3 * Hepatic: Total Bilirubin \</= upper limit of normal (ULN), alanine transaminase (AST) and alanine transaminase (ALT) and alkaline phosphatase must be within the range allowing for eligibility. In determining eligibility the more abnormal of the 2 values (AST or ALT) should be used. * Women of childbearing potential must have a negative pregnancy test. * Patients of childbearing potential must be willing to consent to using effective contraception while on treatment and for 3 months following the completion of treatment.
Exclusion criteria
Prior treatment with Docetaxel or Avastin * Concurrent immunotherapy or hormonal therapy for the specific purpose of treatment for the ovarian cancer. Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to enrollment in order for the patient to be eligible to participate in this trial. Continuation of hormonal replacement therapy is allowed. * Peripheral neuropathy \>/= grade 2 * History of a severe hypersensitivity reaction to Docetaxel, Avastin, or to other drugs formulated with polysorbate (Tween) 80. * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study of Avastin * Blood pressure of \>150/100 mmHg Unstable angina * New York Heart Association (NYHA) Grade II or greater congestive heart failure * History of myocardial infarction within 6 months prior to Day 1 * History of stroke within 6 months prior to Day 1 * Clinically significant peripheral vascular disease * Evidence of bleeding diathesis or coagulopathy * Presence of central nervous system or brain metastases * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study * Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0 * Pregnant (positive pregnancy test) or lactating * Urine protein: creatinine ratio \>/= 1.0 at screening * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0 * Serious, non-healing wound, active ulcer, or untreated bone fracture * Evidence of malignancy in the last 5 years, other than nonmelanoma cutaneous carcinomas * History of hemoptysis (bright red blood of 1/2 teaspoon or more) within last 3 months * Patients believed to possibly be at higher than average risk of perforation will be excluded from study. This includes symptoms or findings of partial or complete bowel obstruction, history of fistula, patients requiring parenteral nutrition and hydration, and those with history of prior perforation due to tumor or perforation within last 6 months from other causes. * Inability to comply with study and/or follow-up procedures. * Patients who are not on a stable dose of anticoagulation therapy. Patients who are on a stable anticoagulation regimen, including coumadin or low molecular-weight heparin, will not be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Six Month Progression Free Survival (PFS) | 6 months per participant | Percentage of participants with PFS at six months. PFS: Period from study entry until disease progression, death due to disease progression, or date of last contact. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, progression of non-target lesions, or the appearance of one or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival | Up to 5 years | PFS: Period from study entry until disease progression, death due to disease progression, or date of last contact. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, progression of non-target lesions, or the appearance of one or more new lesions. |
| Overall Response Rate (RR) | Up to 5 years | Overall Response: Complete Response (CR) + Partial Response (PR). To determine the response rate (RR) of the investigational treatment regimen. Response and progression were evaluated in the study by using the Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) method or modified Rustin Criteria for CA-125 measurements. |
| Occurrence of Grade 3 or 4 Toxicity | Up to 4 years | Number of participants with Grade 3 or 4 Toxicity based on 278 treatment cycles. Toxicity was graded per the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. |
| Overall Survival (OS) | Up to 5 years | Overall Survival (OS): defined as observed length of life from entry onto the protocol to death, or for living patients, date of last contact (regardless of whether or not this contact is on a subsequent protocol). Survival (PFS and OS) were analyzed using the Kaplan-Meier method with standard errors based on Greenwood's formula. |
Countries
United States
Participant flow
Recruitment details
Between March 2007 and February 2011, 45 patients were screened.
Participants by arm
| Arm | Count |
|---|---|
| Avastin and Docetaxel Combination Therapy: Immunotherapy (Avastin) and Chemotherapy (Docetaxel) as outlined in Intervention descriptions. Avastin: 15 mg/kg, In 100 ml normal saline (NS) IV infusion over 90 +/- 15 minutes, Day 1, every 21 day cycle. Docetaxel: 40 mg/m\^2, In 250 ml 5% dextrose in pure water (D5W) or NS IV infusion over 1 hour in a non-pvc container and through a polyethylene-lined set, Day 1, 8, every 21 day cycle. Response assessment every 3 cycles (9 weeks). | 41 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | ineligible histology | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Avastin and Docetaxel |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 33 Participants |
| Age, Continuous | 58.2 years |
| Region of Enrollment United States | 41 participants |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 41 / 41 |
| serious Total, serious adverse events | 27 / 41 |
Outcome results
Primary
Six Month Progression Free Survival (PFS)
Percentage of participants with PFS at six months. PFS: Period from study entry until disease progression, death due to disease progression, or date of last contact. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, progression of non-target lesions, or the appearance of one or more new lesions.
Time frame: 6 months per participant
Population: All evaluable participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avastin and Docetaxel | Six Month Progression Free Survival (PFS) | 43.9 percentage of participants |
Secondary
Median Progression Free Survival
PFS: Period from study entry until disease progression, death due to disease progression, or date of last contact. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, progression of non-target lesions, or the appearance of one or more new lesions.
Time frame: Up to 5 years
Population: All evaluable participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avastin and Docetaxel | Median Progression Free Survival | 5.2 months |
Secondary
Occurrence of Grade 3 or 4 Toxicity
Number of participants with Grade 3 or 4 Toxicity based on 278 treatment cycles. Toxicity was graded per the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Time frame: Up to 4 years
Population: All evaluable participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avastin and Docetaxel | Occurrence of Grade 3 or 4 Toxicity | 27 participants |
Secondary
Overall Response Rate (RR)
Overall Response: Complete Response (CR) + Partial Response (PR). To determine the response rate (RR) of the investigational treatment regimen. Response and progression were evaluated in the study by using the Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) method or modified Rustin Criteria for CA-125 measurements.
Time frame: Up to 5 years
Population: Response Rate (RR) evaluable patients included all patients who received at least 2 cycles of treatment and at least one tumor assessment or had demonstrated clinical progression.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avastin and Docetaxel | Overall Response Rate (RR) | 22 participants |
Secondary
Overall Survival (OS)
Overall Survival (OS): defined as observed length of life from entry onto the protocol to death, or for living patients, date of last contact (regardless of whether or not this contact is on a subsequent protocol). Survival (PFS and OS) were analyzed using the Kaplan-Meier method with standard errors based on Greenwood's formula.
Time frame: Up to 5 years
Population: All evaluable participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avastin and Docetaxel | Overall Survival (OS) | 12.4 months |