Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cancer
Conditions
Keywords
bevacizumab, paclitaxel, carboplatin, ovarian, cancer, fallopian tube, primary peritoneal
Brief summary
The purpose of this study is to determine the maximum tolerated dose (MTD) of intravenous weekly paclitaxel given with intravenous carboplatin and bevacizumab in patients with epithelial ovarian, primary peritoneal, or fallopian tube carcinoma that are to receive neoadjuvant chemotherapy (prior to surgical cytoreduction). Patients will then undergo surgery which will allow an objective measure of response to the above regimen as well as assessment of surgical outcomes.
Detailed description
Phase I study proposed to evaluate: * Tolerability of IV regimen carboplatin, paclitaxel and bevacizumab in the neoadjuvant setting prior to surgery. * Safety/Toxicity of IV regimen in this patient population * Treatment is Carboplatin area under the concentration curve (AUC) 5, Bevacizumab 15mg/m2, and starting dose of paclitaxel of 60mg/m2 and will be escalated in intervals of 10mg/m2 to a maximum dose of 80mg/m2. * Patients will receive cycles 1-3 of carboplatin, bevacizumab, and paclitaxel and then cycle 4 will be carboplatin and paclitaxel followed by surgical intervention within 6 weeks of cycle 4. * Post surgical treatment per physician discretion
Interventions
DRUGcarboplatin
Carboplatin AUC 5.0 or 6.0 will be administered on day 1 during cycle 1-3. Treatment cycle consists of 21 days duration.
DRUGBevacizumab
Bevacizumab 15 mg/kg administered on Day 1 during cycle 1-3. Treatment cycle consists of 21 days duration.
DRUGPaclitaxel
60-80 mg/m2 administered on Day 1, 8 & 15 during cycle 1-3. Treatment cycle consists of 21 days duration.
Sponsors
Genentech, Inc.
Ritu Salani
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* histology,cytologically diagnosed epithelial ovarian, primary peritoneal or fallopian tube cancer * FIGO (International Federation of Gynecology and Obstetrics stage III or IV disease * GOG (Gynecologic Oncology Group) Performance Status 0,1,2 * No prior surgery for their malignancy * Adequate bone marrow function * Platelet count greater than or equal to 100,000 * Renal Function: Creatinine \< 1.5 institutional upper limit normal * Hepatic Function: Bilirubin less than 1.5 ULN (upper limit of normal) * Hepatic Function: SGOT (serum glutamate oxaloacetate transaminase) and Alkaline Phosphate * Neurologic Function: Neuropathy less than CTCAE (Common Toxicity Criteria for Adverse Effects)grade 1 * Coagulation Functions: INR\<1.5 and PTT ,1.2 times the upper limit of normal * Measurable disease
Exclusion criteria
* Previous cancer related surgery * Received prior chemotherapy, immunotherapy, radiotherapy, hormonal therapy or biologic therapy for their ovarian, fallopian tube or primary peritoneal cancer. * Borderline ovarian tumors, recurrent epithelial ovarian or primary peritoneal cancer or non-epithelial ovarian are not eligible. * Other cancers within 5 years (other than non-melanoma skin cancer) * Acute Hepatitis or end stage liver disease * History of prior gastrointestinal perforation * Evidence of abdominal free air not explained by paracentesis * Sign or symptoms of gastrointestinal obstruction * Active bleeding or pathologic conditions that carry high risk of bleeding * CNS (Central Nervous System) disease * Clinically Significant cardiovascular disease * Known hypersensitivity to Chinese Hamster ovary cell products or other recombinant human or humanized antibodies * Clinically significant proteinuria. * Hypertensive crises or hypertensive encephalopathy * History of hemoptysis * Any non-study related invasive procedure within 28 days fo first date of bevacizumab * GOG performance status 3 or 4 * Patients who are pregnant or nursing. * Under the age of 18 * Received prior treatment of bevacizumab or any anti-VEGF (vascular endothelial growth factor) drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerated Dose | Up to 6 months | To determine the maximum tolerated dose of carboplatin AUC5 administered Day 1 Cycles 1-4, weekly paclitaxel 60-80mg/m2 administered on Day 1, 8,and 15 for 3 weeks cycles 1-4, bevacizumab 15mg/kg administered Day 1 Cycles 1-3 prior to surgical intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity and Response Rates Based on Imaging and Surgical Outcomes | Up to 6 months | Determine the safety/toxicity of this regimen in this patient population. Estimate the percent of patients undergoing successful cytoreductive surgery to optimal disease (\<1 cm greatest tumor diameter) following neoadjuvant chemotherapy with carboplatin, paclitaxel and bevacizumab in patients with epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer. Assess the 30 day morbidity and mortality following surgical intervention. To describe the response rate for patients treated with neoadjuvant carboplatin, weekly paclitaxel, and bevacizumab using RECIST and GCIG response criteria prior to surgical intervention. Response was determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Countries
United States
Participant flow
Recruitment details
Patients were enrolled from January to December 2011.
Pre-assignment details
Patients with a histologically or cytologically confirmed EOC with radiographic evidence of advanced disease, consistent with FIGO stage IIIC or IV.
Participants by arm
| Arm | Count |
|---|---|
| Arm I * Chemotherapy Cycles 1-3: All patients will receive 3 cycles of carboplatin, weekly paclitaxel and bevacizumab. Cycles will be administered every 21 days.
* Chemotherapy Cycle 4: Patients will receive carboplatin and paclitaxel without bevacizumab for cycle 4. Radiologic imaging will be obtained pretreatment and after cycle 4.
* Surgery: After 4 cycles of chemotherapy patients will be evaluated for surgical exploration. Patients who complete treatment with neoadjuvant chemotherapy and are medically fit, will undergo maximal tumor cytoreduction. Surgery should be undertaken at least 28 days after the administration of bevacizumab.
* Post-Surgical Chemotherapy: Following surgery, chemotherapy will be at the discretion of the treating physician and will not be part of the study outcomes. There currently is no standard therapy for patients with ovarian cancer after undergoing interval debulking, therefore, this will be at the discretion of | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Arm I |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 9 patients |
| Sex: Female, Male Female | 9 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 | 7 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Tolerated Dose
To determine the maximum tolerated dose of carboplatin AUC5 administered Day 1 Cycles 1-4, weekly paclitaxel 60-80mg/m2 administered on Day 1, 8,and 15 for 3 weeks cycles 1-4, bevacizumab 15mg/kg administered Day 1 Cycles 1-3 prior to surgical intervention.
Time frame: Up to 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Tolerated Dose | 80 mg/m^2 |
Secondary
Toxicity and Response Rates Based on Imaging and Surgical Outcomes
Determine the safety/toxicity of this regimen in this patient population. Estimate the percent of patients undergoing successful cytoreductive surgery to optimal disease (\<1 cm greatest tumor diameter) following neoadjuvant chemotherapy with carboplatin, paclitaxel and bevacizumab in patients with epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer. Assess the 30 day morbidity and mortality following surgical intervention. To describe the response rate for patients treated with neoadjuvant carboplatin, weekly paclitaxel, and bevacizumab using RECIST and GCIG response criteria prior to surgical intervention. Response was determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Up to 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I | Toxicity and Response Rates Based on Imaging and Surgical Outcomes | Partial Responses | 9 patients |
| Arm I | Toxicity and Response Rates Based on Imaging and Surgical Outcomes | Dose Limiting Toxicities | 0 patients |
| Arm I | Toxicity and Response Rates Based on Imaging and Surgical Outcomes | Optimal debulking achieved | 9 patients |