Multicenter Phase III Randomized Study With Second Line Chemotherapy Plus or Minus Bevacizumab in Patients With Platinum Sensitive Epithelial Ovarian Cancer Recurrence After a Bevacizumab/Chemotherapy First Line
Overview
- Phase
- Phase 3
- Intervention
- Paclitaxel
- Conditions
- Recurrent Ovarian Cancer
- Sponsor
- National Cancer Institute, Naples
- Enrollment
- 406
- Locations
- 76
- Primary Endpoint
- progression free survival
- Status
- Active, not recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
Bevacizumab has been found to prolong progression free survival in first line, and more recently, in second line treatment for platinum sensitive ovarian cancer patients who had not received prior treatment with bevacizumab.
Recently reported data suggest that patients with colon cancer who receive bevacizumab in more than one line of therapy (beyond progression) have better results. In ovarian cancer, the role of bevacizumab administered in both first and second-line therapies needs to be defined.
This study aims to evaluate whether administering bevacizumab in combination with chemotherapy in second-line therapy to patients with recurrent ovarian cancer who have received first-line bevacizumab will be more effective than chemotherapy alone.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female patients ≥18 years of age.
- •Patients with histologically confirmed epithelial ovarian or fallopian tube carcinoma or primary peritoneal carcinoma, including mixed Mullerian Tumours
- •Recurrence or progression at least 6 months after the last chemotherapy cycle of a first line carboplatin + paclitaxel chemotherapy including bevacizumab (recurrence or progression might occur either during or after bevacizumab as maintenance)
- •Patients can be included if they have a RECIST progression, with either measurable or non-measurable disease
- •ECOG (Eastern Cooperative Oncology Group Performance) Status of 0-
- •Life expectancy of at least 12 weeks.
- •Signed informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of the patient's awareness and willingness to comply with the study requirements including blood samples for molecular analyses.
- •Availability of tumour samples for molecular analyses from primary surgery (mandatory) and secondary surgery (when available)
Exclusion Criteria
- •Cancer related
- •Ovarian tumours with low malignant potential (i.e. borderline tumours)
- •History or evidence of synchronous primary endometrial carcinoma, unless all of the following criteria related to the endometrial carcinoma are met:
- •stage ≤Ia
- •no more than superficial myometrial invasion
- •no lymphovascular invasion
- •not poorly differentiated (grade 3 or papillary serous or clear cell carcinoma).
- •Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.
- •Prior current or planned treatment:
- •More than one previous chemotherapy line
Arms & Interventions
chemotherapy
Combination chemotherapy with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC (area under curve) 5 on day 1 every 4 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days; * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days.
Intervention: Paclitaxel
chemotherapy
Combination chemotherapy with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC (area under curve) 5 on day 1 every 4 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days; * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days.
Intervention: Carboplatin
chemotherapy
Combination chemotherapy with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC (area under curve) 5 on day 1 every 4 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days; * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days.
Intervention: pegylated liposomal doxorubicin
chemotherapy
Combination chemotherapy with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC (area under curve) 5 on day 1 every 4 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days; * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days.
Intervention: Gemcitabine
Chemotherapy and bevacizumab
Combination chemotherapy AND bevacizumab with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC 5 on day 1 every 4 weeks and Bevacizumab 10 mg/kg i.v. on Day 1 every 2 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks;L * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks. Patients whose disease has not progressed after the initial six cycles of combination treatment will continue bevacizumab, at 15 mg/kg every 3 weeks until disease progression,unacceptable toxicity or patient withdrawn.
Intervention: Bevacizumab
Chemotherapy and bevacizumab
Combination chemotherapy AND bevacizumab with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC 5 on day 1 every 4 weeks and Bevacizumab 10 mg/kg i.v. on Day 1 every 2 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks;L * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks. Patients whose disease has not progressed after the initial six cycles of combination treatment will continue bevacizumab, at 15 mg/kg every 3 weeks until disease progression,unacceptable toxicity or patient withdrawn.
Intervention: Paclitaxel
Chemotherapy and bevacizumab
Combination chemotherapy AND bevacizumab with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC 5 on day 1 every 4 weeks and Bevacizumab 10 mg/kg i.v. on Day 1 every 2 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks;L * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks. Patients whose disease has not progressed after the initial six cycles of combination treatment will continue bevacizumab, at 15 mg/kg every 3 weeks until disease progression,unacceptable toxicity or patient withdrawn.
Intervention: Carboplatin
Chemotherapy and bevacizumab
Combination chemotherapy AND bevacizumab with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC 5 on day 1 every 4 weeks and Bevacizumab 10 mg/kg i.v. on Day 1 every 2 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks;L * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks. Patients whose disease has not progressed after the initial six cycles of combination treatment will continue bevacizumab, at 15 mg/kg every 3 weeks until disease progression,unacceptable toxicity or patient withdrawn.
Intervention: pegylated liposomal doxorubicin
Chemotherapy and bevacizumab
Combination chemotherapy AND bevacizumab with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC 5 on day 1 every 4 weeks and Bevacizumab 10 mg/kg i.v. on Day 1 every 2 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks;L * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks. Patients whose disease has not progressed after the initial six cycles of combination treatment will continue bevacizumab, at 15 mg/kg every 3 weeks until disease progression,unacceptable toxicity or patient withdrawn.
Intervention: Gemcitabine
Outcomes
Primary Outcomes
progression free survival
Time Frame: 12 months
assessed by local Investigator
Secondary Outcomes
- overall survival(12 months)
- number of complete or partial responses(6 months)
- worst grade toxicity per patient(evaluated every 3 weeks up to 12 months)
- number of patients taking oral antidiabetic therapy(at baseline)
- number of patients taking antithrombotic therapy(at baseline)
- progression free survival(12 months)