A Phase ?randomized controlled cllinical trial of carboplatin and paclitaxel(OR GEMCITABINE) alone or incombination with bevacizumab (NSC #704865, IND #113912) followed by bevacizumab and secondary cytoreductive surgery in platinum-sensitive, recurrent ovarian, peritoneal primary and follopian tube cancer
- Conditions
- Neoplasms
- Registration Number
- KCT0003484
- Lead Sponsor
- Seoul National University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- Female
- Target Recruitment
- 1052
1. Patients enrolled after August 28, 2011 must be candidates for cytoreductive surgery and consent to have their surgical treatment determined by randomization.(08/29/11)(12/19/11)
2. Patients must have histologic diagnosis of epithelial ovarian carcinoma, peritoneal primary or Fallopian tube carcinoma, which is now recurrent.
3. Patients with the following histologic epithelial cell types are eligible: Serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified (N.O.S.).
4. Patients must have had a complete response to front-line platinum-taxane therapy (at least three cycles).(08/04/08)
- A complete response to front-line chemotherapy must include: negative physical exam, negative pelvic exam and normalization of CA125, if elevated at baseline. Although not required, any radiographic assessment of disease status (e.g. CT, MRI, PET/CT, etc) obtained following the completion of primary therapy (defined in 3.133) should be considered negative for disease.
- All patients must have also had a treatment-free interval without clinical evidence of progressive disease of at least 6 months from completion of front-line chemotherapy (both platinum and taxane). Front-line therapy may have included a biologic agent (i.e. bevacizumab).
- Front-line treatment may include maintenance therapy following complete clinical or pathological response. However, maintenance cytotoxic chemotherapy must be discontinued for a minimum of 6 months prior to documentation of recurrent disease. Patients receiving maintenance biological therapy or hormonal therapy are ELIGIBLE provided their recurrence is documented more than 6 months from primary cytotoxic chemotherapy completion (includes maintenance chemotherapy) AND a minimum 4 weeks has elapsed since their last infusion of biological therapy.(06/22/09)
5. Patient must have clinically evident recurrent disease for the purpose of this study. (08/29/11)
- Measuralbe disease(RECIST) is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be more than or equal to 20 mm when measured by conventional techniques, MRI or CT, or more than or equal to 10 mm when measured by spiral CT.
6. Patients must have adequate:
- Bone marrow function: Absolute neutrophil coucnt (ANC) greater than or equal to 1,500/? , equivalent to Common Toxicity Criteria for Adverse Events v3.0 (CTCAE) Grade 1.
- Platelets greater than or equal to 100,000/mm 3 . (CTCAE Grade 0-1)
- Renal function: Creatinine (non-IDMS) = 1.5 x institutional upper limit normal (ULN), CTCAE Grade 1 (03/15/10) (08/23/10)
- Hepatic function:
Total bilirubin = 1.5 ULN (CTCAE Grade 1)
SGOT/AST and Alkaline Phosphatase = 2.5 times the upper limit of normal in the absence of liver metastasis. SGOT/AST and Alkaline Phosphatase <5.0 times ULN in the presence of liver metastasis.
- Patients must have a urine protein-to-creatinine ratio (UPCR) < 1.0 mg/dL. The UPCR has been found to correlate directly with the amount of protein excreted in a 24 hr urine collection. Specifically, a UPCR of 1.0 is equivalent to 1.0 gram of protein in a 24-hour urine collection. Obtain at least 4 ml of a random urine sample in a sterile container (does not have to be a 24 hour urine). Send the samp
1. Patients who have received more than one previous regimen of chemotherapy (maintenance is not considered a second regimen)
2. Patients receiving concurrent immunotherapy, or radiotherapy
3. Patients who have received prior radiotherapy to any portion of the abdomal cavity or pelvis are excluded
4. Patients whom have already undergone secondary cytoreduction for recurrent disease are excluded
5. Patients with a prior histologic diagnosis of borderline, low malignant potential (grade 0) epithelial carcinoma that was surgically resected and who subsequently developed an unrelated, new invasive epithelial ovarian or peritoneal primary cancer are eligible provided that they meet the criteria listed in Section 3.12
6. Patients who require parenteral hydration or nutrition and have evidence of partial bowel obstruction or perforation
7. Patients who have received prior chemotherapy for any abdominal or pelvic tumor (other than ovarian, fallopian tube, and primary peritoneal) are excluded. (06/22/09) (03/15/10)
8. Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, are excluded, unless all of the following conditions are met: Stage not greater than I-B; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other FIGO Grade 3 lesions
9. Patients with uncontrolled infection
10. Patients with concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy
11. Patients with = grade 2 peripheral neuropathy
12. Patients with a history of allergic reactions to carboplatin and/or paclitaxel or chemically similar compounds. Patients with allergic (hypersensitivity) reactions to these chemotherapeutic agents are NOT excluded IFthey were successfully retreated following a desensitization program or protocol
13. Patients of childbearing potential, not practicing adequate contraception, patients who are pregnant or patients who are nursing are not eligible for this trial. To date, no fetal studies in animal or humans have been performed. The possibility of harm to a fetus is likely. Bevacizumab specifically inhibits VEGF, which is responsible for the formation of new blood vessels during development, and antibodies can cross the placenta. Therefore, bevacizumab should not be administered to pregnant women. In addition, there are unknown immediate and long-term consequences of chemotherapy administration to these women. In addition, surgical exploration as mandated by randomization during pregnancy may cause imminent mortal consequences. Further, it is not known whether bevacizumab is excreted in human milk. Because many drugs are excreted in human milk, bevacizumab should not be administered to nursing women. Subjects will be apprised of the large potential risk to a developing fetus.
14. Patients with other invasive malignancies, withthe exception of non-melanoma skin cancer, who had (or have) any evidence of the other cancer present within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy.
15. Patients with active bleeding or pathologic conditions that carry high risk of bleeding such as a known bleeding disorder, coagulopathy, or tumor involving major vessels.
16. Patients with a history or evidence upon physical examinatio
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method overall survival
- Secondary Outcome Measures
Name Time Method progression-free survival;quality of life assessment score;Adverse Events