Clinical trial NCT02828618: Trial on Radical Upfront Surgery in Advanced Ovarian Cancer
Official title: Trial on Radical Upfront Surgery in Advanced Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Ovarian Cancer
Lead sponsor: AGO Study Group
Sponsor class: OTHER
First posted: 2016-07-11
Enrollment: 797
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: overall survival (OS)
timeFrame: Patients will be followed up for a minimum of 5 years after registration/randomisation or until death
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Patients will be followed up for a minimum of 5 years after registration/randomisation or until death
measure: Progression-free survival 2 (PFS2)
timeFrame: Patients will be followed up for a minimum of 5 years after registration/randomisation or until death
measure: Time to first subsequent anticancer therapy or death (TFST)
timeFrame: Patients will be followed up for a minimum of 5 years after registration/randomisation or until death
measure: Time to second subsequent anticancer therapy or death (TSST)
timeFrame: Patients will be followed up for a minimum of 5 years after registration/randomisation or until death
measure: Quality of life (QoL)
timeFrame: Patients will be followed up for a minimum of 5 years after registration/randomisation or until death
measure: Documentation of surgical complications
timeFrame: Patients will be followed up for 1 year after surgery or until death
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Copenhagen
country: Denmark
facility: University Hospital, Rigshospitalet
city: Bordeaux
country: France
facility: Institut Bergonié
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou (HEGP)
city: Villejuif
country: France
facility: Institute Gustave Roussy
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Klinik für Gynäkologie
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden, Klinik & Poliklinik f. Frauenheilkunde & Geburtshilfe
city: Dusseldorf
country: Germany
facility: Kaiserswerther Diakonie; Florence-Nightingale-Hospital
city: Essen
country: Germany
facility: Kliniken Essen-Mitte, Evang. Huyssens-Stiftung, Klinik für Gynäkologie und gyn. Onkologie
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Gynäkologie
city: München
country: Germany
facility: Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der Universität München
city: München
country: Germany
facility: Klinikum rechts der Isar, Frauen- und Poliklinik
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Milano
country: Italy
facility: European Institute of Oncology; Gynecologic Cancer Surgery
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale Tumori - Milan
city: Naples
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori di Napoli
city: Lund
country: Sweden
facility: Skane University Hospital
city: Solna
country: Sweden
facility: Karolinska University Hospital
city: London
country: United Kingdom
facility: Imperial College London, Hammersmith Hospital, Surgery&Cancer
Study officials:
affiliation: AGO Study Group
name: Sven Mahner, Professor MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.