This study consists of three parts, whereas Part 1 and Part 2 are performed in Germany only, and Part 3 is a multinational trial. All patients with suspicion of advanced ovarian cancer are detected in the participating study centers in a pre-screening. The study centers will register all patients with suspected ovarian cancer in a screening log. After the patients have given informed consent, they can be enrolled in different parts of the study. TRUST-Trial: This part compares two strategies in the therapy of advanced ovarian cancer. En detail, this part of the trial will evaluate if one of two strategies of timing surgery within the therapeutic procedures may show any significant advances in terms of overall survival over the other.
Both randomised groups are treated with surgery for complete resection following guideline recommendations and including median laparotomy, complete adhesiolysis, hysterectomy, bilateral salpingo-oophorectomy, omentectomy and (partial) resection of all affected organs (e.g. small or large bowel, peritoneum, spleen, pancreas, peritoneum, urinary tract etc.) as well as pelvic and paraaortic lymphadenectomy if indicated. Patients with significant pleural effusion (\>500 mL in the right chest or any pleural effusion in the left chest, assessed either through ultrasound or CT scan) need to undergo video assisted thoracoscopy or open assessment of the pleura prior or during debulking surgery to detect and if possible remove intrathoracic disease. Group 1: Primary debulking surgery Patients allocated to the primary debulking group undergo surgery followed by 6 cycles of platinum and taxane based chemotherapy. Recommended systemic treatment Group 1: It is recommended to start systemic treatment after sufficient regeneration from surgery \[45\], which will be ideally 2 to 6 weeks (but at the latest 8 weeks) after surgery. The following treatments are recommended: 1. Participation in a prospective randomized trial, as long as participation is possible in case of randomization in either arm of the current study 2. Carboplatin AUC 5-6 / paclitaxel 175 mg/m² q21 / bevacizumab 15mg/KG q21, 6 cycles followed by bevacizumab maintenance therapy for a total of 15 months or until disease progression. 3. Carboplatin AUC 5-6 / paclitaxel 175 mg/m² q21, 6 cycles. Substitution of paclitaxel by docetaxel (75mg/m²) in cases of contraindications to paclitaxel is possible. Maintenance/consolidation therapy inside prospective trials or according to national standard treatments is allowed. Additional treatment outside prospective studies is not recommended. 4. Carboplatin AUC 5 - 6, q21 , 6 cycles in the case of contraindications of combination chemotherapy Group 2: Interval debulking surgery Patients allocated to the interval debulking surgery group undergo biopsy to confirm ovarian cancer and then 3 cycles of neoadjuvant preoperative platinum and taxane based chemotherapy. Then interval debulking surgery is performed followed by 3 cycles of postoperative platinum and taxane based chemotherapy Recommended systemic treatment Group 2: It is recommended to start systemic treatment as soon as possible after biopsy confirmation of ovarian cancer. The following treatments are recommended for neoadjuvant chemotherapy: 1. Participation in a prospective randomized trial, as long as participation is possible in case of randomization in either arm of the current study 2. Carboplatin AUC5-6 / paclitaxel 175 mg/m² q21, 3 cycles. Substitution of paclitaxel by docetaxel (75mg/m²) in cases of contraindications to paclitaxel is possible. 3. Carboplatin AUC 5-6, q21 , 3 cycles in the case of contraindications of combination chemotherapy It is recommended to start postoperative chemotherapy after sufficient regeneration from interval debulking surgery, which will be ideally 2 to 6 weeks after surgery. The following treatments are recommended: 1. Participation in a prospective randomized trial, as long as participation is possible in case of randomization in either arm of the current study 2. Carboplatin AUC 5-6 / paclitaxel 175 mg/m² q21 / bevacizumab 15mg/KG q21, 3 cycles followed by bevacizumab maintenance therapy for a total of 15 months or until disease progression. 3. Carboplatin AUC5-6 / paclitaxel 175 mg/m² q21, 3 cycles. Substitution of paclitaxel by docetaxel (75mg/m²) in cases of contraindications to paclitaxel is possible. Maintenance/consolidation therapy inside prospective trials or according to national standard treatments is allowed. Additional treatment outside prospective studies is not recommended. 4. Carboplatin AUC 5-6, q21 , 3 cycles in the case of contraindications of combination chemotherapy
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
797
PDS with maximum effort to achieve the goal of complete gross resection
6 cycles of standard chemotherapy after Primary Debuling Surgery
Timing of surgery after 3 cycles of standard NACT
IDS with maximum effort to achieve the goal of complete gross resection after NACT
3 more cycles (for a total of 6) of standard chemotherapy after IDS
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Medical University of Vienna
Vienna, Austria
University Hospital, Rigshospitalet
Copenhagen, Denmark
Institut Bergonié
Bordeaux, France
Hôpital Européen Georges Pompidou (HEGP)
Paris, France
Institute Gustave Roussy
Villejuif, France
Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Klinik für Gynäkologie
Berlin, Germany
Universitätsklinikum Carl Gustav Carus Dresden, Klinik & Poliklinik f. Frauenheilkunde & Geburtshilfe
Dresden, Germany
Kaiserswerther Diakonie; Florence-Nightingale-Hospital
Düsseldorf, Germany
Kliniken Essen-Mitte, Evang. Huyssens-Stiftung, Klinik für Gynäkologie und gyn. Onkologie
Essen, Germany
...and 10 more locations
overall survival (OS)
To compare the overall survival (OS) after primary debulking surgery (PDS) versus interval debulking surgery (IDS) following neoadjuvant chemotherapy (NACT) in patients with FIGO (2014) stage IIIB-IVB ovarian, tubal, and peritoneal carcinoma. The primary endpoint overall survival time is calculated from the date of randomization until the date of death from any cause or date of last contact (censored observation).
Time frame: Patients will be followed up for a minimum of 5 years after registration/randomisation or until death
Progression-free survival (PFS)
Progression-free survival time is calculated from the date of randomization until the date of first progressive disease or death, whichever occurs first or date of last contact (censored observation). Progressive disease is defined as clinical or imaging-detected tumor progression or death in cases without prior documented tumor progression.
Time frame: Patients will be followed up for a minimum of 5 years after registration/randomisation or until death
Progression-free survival 2 (PFS2)
PFS2 time is calculated from the date of randomization until the date of second progressive disease or death, whichever occurs first or date of last contact (censored observation).
Time frame: Patients will be followed up for a minimum of 5 years after registration/randomisation or until death
Time to first subsequent anticancer therapy or death (TFST)
Time to first subsequent anticancer therapy is calculated from the date of randomization until the starting date of the first subsequent anticancer therapy or death, whichever occurs first or date of last contact (censored observation). Maintenance treatments following a cytostatic treatment are not considered separate treatment lines.
Time frame: Patients will be followed up for a minimum of 5 years after registration/randomisation or until death
Time to second subsequent anticancer therapy or death (TSST)
Time to second subsequent anticancer therapy is calculated from the date of randomization until the starting date of the second subsequent anticancer therapy or death, whichever occurs first or date of last contact (censored observation). Maintenance treatments following a cytostatic treatment are not considered separate treatment lines.
Time frame: Patients will be followed up for a minimum of 5 years after registration/randomisation or until death
Quality of life (QoL)
Quality of life (QoL) as measured by EORTC QLQ-C30 (Version 3), EORTC QLQ-OV28, EQ-5D-3L
Time frame: Patients will be followed up for a minimum of 5 years after registration/randomisation or until death
Documentation of surgical complications
Assessment of safety: documentation of surgical complications 28 days after surgery and 1 year after surgery.
Time frame: Patients will be followed up for 1 year after surgery or until death
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