A Prospective Randomised Phase III Trial to Evaluate Optimal Treatment Duration of First-line Bevacizumab in Combination With Carboplatin and Paclitaxel in Patients With Primary Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer
Overview
- Phase
- Phase 3
- Intervention
- Bevacizumab
- Conditions
- Genital Diseases, Female
- Sponsor
- AGO Study Group
- Enrollment
- 927
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to determine whether the early and continuous addition of bevacizumab for up to 30 months to the standard chemotherapy is more effective than the early and continuous addition of bevacizumab for up to 15 months.
Detailed Description
Determination whether the early and continuous addition of bevacizumab for up to 30 months to the standard chemotherapy is more effective than the early and continuous addition of bevacizumab for up to 15 months
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed written informed consent obtained prior to initiation of any study specific procedures and treatment as confirmation of the patients awareness and willingness to comply with the study requirements
- •Primary diagnosis is confirmed by specialized pathology review (Germany only)
- •Females aged ≥ 18 years
- •Histologically confirmed, newly diagnosed
- •Epithelial ovarian carcinoma
- •Fallopian tube carcinoma
- •Primary peritoneal carcinoma AND FIGO stage IIb - IV (all grades and all histological types)
- •Patients should have already undergone surgical debulking, by a surgeon experienced in the management of ovarian cancer, with the aim of maximal surgical cytoreduction according to the GCIG Conference Consensus Statement. There must be no planned surgical debulking prior to disease progression. Patients with stage III and IV disease in whom initial surgical debulking was not appropriate or possible will still be eligible providing
- •the patient has a histological diagnosis and
- •debulking surgery prior to disease progression is not foreseen
Exclusion Criteria
- •Non-epithelial origin of the ovary, the fallopian tube or the peritoneum
- •Borderline tumours (tumours of low malignant potential) and FIGO stage Ia - IIa tumours
- •Planned intraperitoneal cytotoxic chemotherapy
- •Prior systemic anti-cancer therapy for ovarian cancer (for example chemotherapy, monoclonal antibody therapy, tyrosine kinase inhibitor therapy or hormonal therapy)
- •Surgery (including open biopsy) within 4 weeks prior to anticipated first dose of bevacizumab (allowing for the fact that bevacizumab can be omitted from the first cycle of chemotherapy). It is strongly recommended that an interval of 7 days is left between the insertion of any central venous access devices (CVADs) and the onset of bevacizumab treatment.
- •Any planned surgery during the study treatment period plus 4 additional weeks to allow for bevacizumab clearance
- •Uncontrolled hypertension (sustained elevation of BP systolic \> 150mmHg and/or diastolic \> 100mmHg despite antihypertensive therapy)
- •Any previous radiotherapy to the abdomen or pelvis
- •Significant traumatic injury during 4 weeks preceding the potential first dose of bevacizumab
- •History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression.
Arms & Interventions
Control Arm
Patients receive bevacizumab iv followed by paclitaxel iv and carboplatin iv on day 1. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab iv alone every 3 weeks for 16 cycles.
Intervention: Bevacizumab
Control Arm
Patients receive bevacizumab iv followed by paclitaxel iv and carboplatin iv on day 1. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab iv alone every 3 weeks for 16 cycles.
Intervention: Paclitaxel
Control Arm
Patients receive bevacizumab iv followed by paclitaxel iv and carboplatin iv on day 1. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab iv alone every 3 weeks for 16 cycles.
Intervention: Carboplatin
Control Arm
Patients receive bevacizumab iv followed by paclitaxel iv and carboplatin iv on day 1. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab iv alone every 3 weeks for 16 cycles.
Intervention: specialized pathology review (Germany only)
Research Arm
Patients receive bevacizumab iv followed by paclitaxel iv and carboplatin iv on day 1. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab iv alone every 3 weeks for 38 cycles.
Intervention: Paclitaxel
Research Arm
Patients receive bevacizumab iv followed by paclitaxel iv and carboplatin iv on day 1. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab iv alone every 3 weeks for 38 cycles.
Intervention: Carboplatin
Research Arm
Patients receive bevacizumab iv followed by paclitaxel iv and carboplatin iv on day 1. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab iv alone every 3 weeks for 38 cycles.
Intervention: specialized pathology review (Germany only)
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: every 12 weeks until progression or up to 30 months, thereafter every 6 months
Secondary Outcomes
- Objective response rate (ORR)(every 12 weeks until progression or up to 30 months, thereafter every 6 months)
- Overall survival (OS)(every 3 weeks, 31 months after start of treatment, thereafter every 6 months)
- Health related Quality of life (QoL)(baseline, then every 12 weeks until progression, 31 months after start of treatment or if applicable 4 weeks after last dose of bevacizumab (whichever occurs later))
- Safety and tolerability, i.e. type, frequency, severity and duration of adverse reactions(every 3 weeks, 31 months after start of treatment or if applicable 4 weeks after last dose of bevacizumab (whichever occurs later))
- Translational Research - Tumor Tissue Block(Assessment at end of study planned)
- Translational Research - Complementary and Alternative Treatment Questionnaires(baseline, 6 months and 12 months after start of treatment, if required at timepoint of treatment termination)