Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma
Conditions
Keywords
Ovarian Cancer, Primary Debulking Surgery, Neoadjuvant chemotherapy, Poly-adenosine Ribose Phosphate Inhbitors (PARPi), Bevacizumab
Brief summary
Optimal Timing of Surgery combined with Maintenance Therapy in the Front-line Treatment of Advanced Ovarian Cancer
Detailed description
The purpose of this trial is to answer the fundamental question 'The Optimal Timing of Surgery' combined with Bevacizumab or Poly-adenosine Ribose Phosphate Inhbitors (PARPi), in the circumstance of primarily diagnosed advanced epithelial ovarian cancer, fallopian tube cancer and primary peritoneal carcinoma.
Interventions
PROCEDUREPrimary debulking surgery
Primary debulking surgery with a maximum cytoreduction, then followed by 6 cycles of Paclitaxel 175mg/m2 or Docetaxel 60-75 mg/m2 plus Carboplatin AUC (area under the curve) 5.
PROCEDURENeoadjuvant chemotherapy
3 cycles of Paclitaxel 175mg/m2 or Docetaxel 60-75 mg/m2 plus Carboplatin AUC (area under the curve) 5, Interval debulking surgery with a maximal cytoreduction of complete gross resection, then followed by another 3 cycles of chemotherapy.
DRUGPARP inhibitor
For patients with BRCA mutated, maintenance therapy of PARP inhibitors following CR/PR after first-line chemotherapy. In this trial, Olaparib 300mg p.o. twice daily is suggested after the front-line therapy.
DRUGBevacizumab
For patients without BRCA mutated, maintenance therapy of Bevacizumab following CR/PR after first-line chemotherapy. In this trial, Bevacizumab 7.5mg per kilogram intravenous once every 3 weeks is suggested after the front-line therapy.
Sponsors
Fudan University
Shanghai Gynecologic Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Females aged ≥ 18 years. * Pathologic confirmed stage IIIC and IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal carcinoma * Low, Middle tumor burden and high tumor burden with cPCI score ≤ 12 based on pre-operative CT or PET/CT examination * Complete cytoreduction can be achieved based on CT or PET/CT examination * Patients must agree to undergo BRCA (breast cancer gene) and HRD (homologous recombination deficiency) testing * Performance status (ECOG 0-2) * Adequate bone marrow, renal and hepatic function to receive chemotherapy and subsequent surgery: 1. white blood cells \>3,000/µL, absolute neutrophil count ≥1,500/µL, platelets ≥100,000/µL, hemoglobin ≥9 g/dL, 2. serum creatinine \<1.25 x upper normal limit (UNL) or creatinine clearance ≥60 mL/min according to Cockroft-Gault formula or to local lab measurement, 3. serum bilirubin \<1.25 x UNL, AST(SGOT) and ALT(SGPT) \<2.5 x UNL. * Comply with the study protocol and follow-up. * Patients who have given their written informed consent.
Exclusion criteria
* Non-epithelial ovarian malignancies and borderline tumors * Low grade ovarian cancer * Mucinous ovarian cancer * Complete cytoreduction cannot be achieved according to preoperative evaluation, including pulmonary and hepatic parenchymal metastases, unresectable extensive pleural metastases, multiple thoracic lymph nodes metastases, brain or bone metastases * Patient has a known hypersensitivity to the components of olaparib/bevacizumab or its excipients * Synchronous or metachronous (within 5 years) malignancy other than carcinoma in situ, thyroid carcinoma, or breast carcinoma (without any signs of relapse or activity, early-stage). * Any other concurrent medical conditions contraindicating surgery or chemotherapy that could compromise adherence to the protocol. * Other conditions, such as religious, psychological, and other factors, that could interfere with the provision of informed consent, compliance to study procedures, or follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3-year overall survival | Participants will be followed for at least 3 years after randomization | The proportion of patients alive at 3 years after entry into the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | Participants will be followed for at least 3 years after randomization | Time from entry into the study to the diagnosis of the first progression or recurrence or death, whichever occurs first |
| Post-operative complications | Participants will be followed up to 3 months after randomization | The surgical complications will be evaluated at 30-day, 60-day, 90-day after upfront cytoreductive surgery or interval debulking surgery |
| Quality of life assessments | Participants will be followed for at least 3 years after randomization | QLQ-C30, FACT-Q (baseline; 6 months, 12 months, 24 months and 36 months after randomization) |
| Overall survival | Participants will be followed for at least 3 years after randomization | Time from entry into the study to any cause of death |
| TFST | Participants will be followed for at least 3 years or death after randomization | Time from the date of randomization until the starting date of the first subsequent anticancer therapy or death, whichever occurred first, whichever occurred first |
| TSST | Participants will be followed for at least 3 years or death after randomization | Time from the date of randomization until the starting date of the second subsequent anticancer therapy or death, whichever occurred first |
| The pattern of the first relapse | Participants will be followed for at least 3 years or death after randomization | The number and sites of the first relapse, including pelvic, abdominal, retroperitoneal lymph nodes, distant metastases and ascites will be compared between the two groups. |
| Accumulated treatment-free survival | Participants will be followed for at least 3 years or death after randomization | Time from the date of randomization to death from any reason, minus the total treatment time of surgery and chemotherapy after randomization (regardless of targeted therapy) |
Countries
China
Contacts
Primary ContactLibing Xiang
Backup ContactRong Jiang
Outcome results
None listed