Trial on Radical Upfront Surgery in Advanced Ovarian Cancer

NCT ID: NCT02828618

Last Updated: 2025-10-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 797 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2025-12-31

Brief Summary

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.

Detailed Description

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

Conditions

Ovarian Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I PDS and chemotherapy

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

Group Type: ACTIVE_COMPARATOR

PDS (Primary Debulkdung Surgery)

Intervention Type: PROCEDURE

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

6 cycles of standard chemotherapy

Intervention Type: PROCEDURE

6 cycles of standard chemotherapy after Primary Debuling Surgery

Arm II Timing of surgery after 3 cycles of SOC CTX

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

Group Type: EXPERIMENTAL

Timing of surgery after 3 cycles of standard NACT, IDS

Intervention Type: PROCEDURE

Timing of surgery after 3 cycles of standard NACT

IDS

Intervention Type: PROCEDURE

IDS with maximum effort to achieve the goal of complete gross resection after NACT

3 cycles of standard chemotherapy

Intervention Type: DRUG

3 more cycles (for a total of 6) of standard chemotherapy after IDS

Interventions

PDS (Primary Debulkdung Surgery)

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

Intervention Type: PROCEDURE

6 cycles of standard chemotherapy

6 cycles of standard chemotherapy after Primary Debuling Surgery

Intervention Type: PROCEDURE

Timing of surgery after 3 cycles of standard NACT, IDS

Timing of surgery after 3 cycles of standard NACT

Intervention Type: PROCEDURE

IDS

IDS with maximum effort to achieve the goal of complete gross resection after NACT

Intervention Type: PROCEDURE

3 cycles of standard chemotherapy

3 more cycles (for a total of 6) of standard chemotherapy after IDS

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• suspected or histologically confirmed, newly diagnosed invasive epithelial ovarian cancer FIGO stage IIIB-IV (IV only if resectable metastasis)
• Females aged ≥ 18 years
• Patients who have given their written informed consent
• Good performance status (ECOG 0/1)
• Good ASA score (1/2)
• Preoperative CA 125/CEA ratio ≥ 25 (if CA-125 is elevated)*
• If <25 and/or biopsy with non-serous, non-endometroid histology, esophago-gastro-duodenoscopy (EGD) and colonoscopy mandatory to exclude gastrointestinal primary cancer
• Assessment of an experienced surgeon, that based on all available information, the patient can undergo the procedure and the tumor can potentially be completely resected
• Adequate bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. This ANC cannot have been induced or supported by granulocyte colony stimulating factors.
• Platelet count ≥ 100 x 109/L.
• Renal function: Serum-Creatinine ≤ 1.5 x institutional upper limit normal (ULN).
• Hepatic function:

• Bilirubin ≤ 1.5 x ULN.
• SGOT ≤ 3 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN.
• Neurologic function: Neuropathy (sensory and motor) less than or equal to CTCAE Grade 1.

Exclusion Criteria

• Non epithelial ovarian malignancies and borderline tumors
• Secondary invasive neoplasms in the last 5 years (except synchronal endometrial carcinoma FIGO IA G1/2, non melanoma skin cancer, breast cancer T1 N0 M0 G1/2) or with any signs of relapse or activity.
• Recurrent ovarian cancer
• Prior chemotherapy for ovarian cancer or abdominal/pelvic radiotherapy
• Unresectable parenchymal lung metastasis, liver metastasis or bulky lymph-nodes in the mediastinum in CT chest and abdomen/pelvis
• Clinical relevant dysfunctions of blood clotting (including drug induced)
• Any significant medical reasons, age or performance status that will not allow to perform the study procedures (estimation of investigator)
• Pregnancy
• Dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent
• Any reasons interfering with regular follow-up

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

AGO Study Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sven Mahner, Professor MD

Role: PRINCIPAL_INVESTIGATOR

AGO Study Group

Locations

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

Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Gynäkologie

Hamburg, , Germany

Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der Universität München

München, , Germany

Klinikum rechts der Isar, Frauen- und Poliklinik

München, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

European Institute of Oncology; Gynecologic Cancer Surgery

Milan, , Italy

Fondazione IRCCS Istituto Nazionale Tumori - Milan

Milan, , Italy

Istituto Nazionale per lo Studio e la Cura dei Tumori di Napoli

Naples, , Italy

Skane University Hospital

Lund, , Sweden

Karolinska University Hospital

Solna, , Sweden

Imperial College London, Hammersmith Hospital, Surgery&Cancer

London, , United Kingdom

Countries

United States; Austria; Denmark; France; Germany; Italy; Sweden; United Kingdom

References

Reuss A, du Bois A, Harter P, Fotopoulou C, Sehouli J, Aletti G, Guyon F, Greggi S, Mosgaard BJ, Reinthaller A, Hilpert F, Schade-Brittinger C, Chi DS, Mahner S. TRUST: Trial of Radical Upfront Surgical Therapy in advanced ovarian cancer (ENGOT ov33/AGO-OVAR OP7). Int J Gynecol Cancer. 2019 Oct;29(8):1327-1331. doi: 10.1136/ijgc-2019-000682. Epub 2019 Aug 15.

Reference Type: DERIVED

PMID: 31420412 (View on PubMed)

Other Identifiers

AGO-OVAR OP.7/TRUST

Identifier Type: -

Identifier Source: org_study_id