Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

PDS with maximum effort to achieve the goal of complete gross resection then followed by 6 cycles of standard chemotherapy

3 cycles of standard NACT followed by IDS with maximum effort to achieve the goal of complete gross resection followed by 3 more cycles (for a total of 6) of standard chemotherapy

PDS with maximum effort to achieve the goal of complete gross resection

PDS (Primary Debulkdung Surgery)

6 cycles of standard chemotherapy after Primary Debuling Surgery

6 cycles of standard chemotherapy

Timing of surgery after 3 cycles of standard NACT

Timing of surgery after 3 cycles of standard NACT, IDS

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

3 cycles of standard chemotherapy

Sven Mahner, Professor MD

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

Trial on Radical Upfront Surgery in Advanced Ovarian Cancer

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).

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.

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 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 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.

Quality of life (QoL) as measured by EORTC QLQ-C30 (Version 3), EORTC QLQ-OV28, EQ-5D-3L

Assessment of safety: documentation of surgical complications 28 days after surgery and 1 year after surgery.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Trial on Radical Upfront Surgery in Advanced Ovarian Cancer	NCT02828618	Ovarian Cancer	PDS (Primary De... 6 cycles of sta... Timing of surge... IDS 3 cycles of sta...	18 Years -	AGO Study Group
Trial on Radical Upfront Surgery in Advanced Ovarian Cancer	NCT02828618	Ovarian Cancer	PDS (Primary De... 6 cycles of sta... Timing of surge... IDS 3 cycles of sta...	18 Years -	AGO Study Group

Spots Global Cancer Trial Database for 6 cycles of standard chemotherapy