Clinical trial NCT05862740: ULTRA-LAP Trial: Laparoscopic Debulking Surgery (LDS) in Advanced Ovarian Cancer
Official title: ULTRA-LAP Trial: Laparoscopic Debulking Surgery (LDS) in Advanced Ovarian Cancer: a Feasibility Prospective Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Ovarian Cancer
Keywords: Ovarian cancer
Advanced ovarian cancer
Debulking surgery
Multivisceral surgery
Laparoscopic debulking surgery
Lead sponsor: Azienda Ospedaliera di Padova
Sponsor class: OTHER
Collaborators: name: University of Padova
First posted: 2023-05-17
Enrollment: 62
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Group A is the study group (completed laparoscopic debulking); Group B (conversion to laparotomy) is the control group in which laparoscopy could not be completed
Primary purpose: TREATMENT

Brief summary: ULTRA-LAP is a prospective study is to investigate the safety, efficacy and feasibility of laparoscopic debulking surgery (LDS) for the treatment of patients with advanced ovarian cancer.

The outcomes to measure are:

* Safety: the rate of patients experiencing intra- and post-operative early and late morbidities (within the hospitalization and up to 60 days from surgery)
* Efficacy: the rate of patients in which the surgical target set pre-operatively (complete resection) is achieved by laparoscopy.
* Feasibility: the rate of patients who have their procedure completed by laparoscopy

Patients will undergo laparoscopic debulking surgery (LDS) if the surgical target can be met. If it cannot be achieved by laparoscopy the surgeon will convert to laparotomy.

Detailed description: The investigators intend to perform a prospective feasibility study on patients with primary diagnosis of advanced ovarian cancer (stage II to IV according to FIGO classification) who are referred to the tertiary cancer centre of the study. The latter is the Department of Gynecology and Obstetrics - Division of Women's and Children's Health - University of Padova - Italy. The statistical sample size calculation identified a minimum of 62 patients. The anticipated enrollment period will be about 4 years.

To confirm the ultimate eligibility to surgery and recruitment in the study, all patients undergo an exploratory laparoscopy (EXL).

The ideal surgical target is complete resection (CR) of all visible disease. Patients who are deemed not amenable to a CR at EXL will start neo-adjuvant chemotherapy. They will be reconsidered for the ULTRA-LAP study at time of interval surgery after 3 cycles of chemotherapy. Criteria for eligibility after neo-adjuvant chemotherapy are the same as per up-front surgery.

All patients recruited in the ULTRA-LAP trial will be discussed at Gynaecologic Oncology Multidisciplinary team (MDT) meeting, where imaging is reviewed and management is agreed. Following MDT decision:

* A Gynaecologic Oncologist will discuss the standard management and the ULTRA-LAP trial at time of out-patient clinic
* The ULTRA-LAP leaflet and consent form will be provided to the patient together with an accurate explanation of the study
* If the patient accepts to enter the study, a study registration form will be filled
* Participation in the study will be confirmed and the forms signed at time of pre-operative assessment and again confirmed at time of in-patient admission ULTRA-LAP trail will include all surgical procedures necessary to accomplish a complete resection (CR) of disease. The most common procedures necessary to obtain a CR are defined by The European Society of Gynaecological Oncology (ESGO), Society of Gynecologic Oncology (SGO) and the The National Institute for Health and Care Excellence (NICE) guidelines. All procedures will be performed by an expert Gynaecologic Oncologist with proven experience and high skills levels in oncological surgery. Once the surgeon realizes that a CR could not be achieved by laparoscopy, but prove to be feasible by laparotomy, the surgery is immediately converted to laparotomy.

Subsequent follow-up:

1. During Recovery:

   - The patients are going to be monitored daily and any relevant complications will be registered, graded (according to Clavien-Dindo classification) and treated.
2. Post recovery:

   * 1 st follow-up visit: At time of hospital's discharge an examination will be performed and, if necessary, further exams will be prescribed as appropriate.
   * 2 nd follow-up visit: following discharge, the next appointment is in the outpatient clinic roughly 15-20 days from the surgery.
   * 3 rd and last visit: at 30 days from the surgery a further appointment will be carried.

At each follow-up appointment the following will be registered:

* Occurrence of complications
* Physical examination
* Changes in normal quality of life.

Achievement of a CR will be determined at time of surgery and confirmed by a pre-chemotherapy CT scan. Should discrepancy arise, CT scan will be reviewed at MDT.

All patients will be closely monitored with a rigorous follow-up program every 90 days for the first two years and then every 120 days for the subsequent 2 years. In addition, all patient could contact the department if any unexpected complications happens between follow-up time.

Eligibility criteria: Inclusion Criteria:

* Patients with advanced epithelial ovarian cancer (II-IV Stage FIGO) candidates to PDS (primary debulking surgery) or IDS (interval debulking surgery: neoadjuvant chemotherapy followed by IDS).
* Participant is willing and able to give informed consent for participation in the study.
* Female aged 18 years or above.
* Primary diagnosis of advanced epithelial ovarian cancer (tubal and peritoneal cancer included).

Exclusion Criteria:

* Comorbidities non-allowing for radical surgery
* Poor Performance Status (Karnofsky Index \< 70)
* Concomitant or past history of malignancy, regardless of treatment status
* Recent or past story of pancreatitis or hepatitis
* Recent or past story of pleural effusion or lung injuries or respiratory failure
* Cardiac major pathologies

Primary outcomes:
measure: Safety: rate of complications/morbidities
timeFrame: 60 days
measure: Efficacy: rate of complete resection (CR) in group 1
timeFrame: 60 days
measure: Feasibility: rate of procedures completed by laparoscopy
timeFrame: 60 days
Secondary outcomes:
measure: Progression Free Survival (PFS).
timeFrame: 5 years
measure: Overall Survival (OS).
timeFrame: 5 years
Other outcomes:
Locations:
city: Padova
country: Italy
facility: Azienda Ospedaliera Universitaria di Padova,
state: Padova, Veneto
Study officials:
affiliation: Azienda Ospedale Università di Padova
name: Roberto Tozzi, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Elattar A, Bryant A, Winter-Roach BA, Hatem M, Naik R. Optimal primary surgical treatment for advanced epithelial ovarian cancer. Cochrane Database Syst Rev. 2011 Aug 10;2011(8):CD007565. doi: 10.1002/14651858.CD007565.pub2.
citation: Shih KK, Chi DS. Maximal cytoreductive effort in epithelial ovarian cancer surgery. J Gynecol Oncol. 2010 Jun;21(2):75-80. doi: 10.3802/jgo.2010.21.2.75. Epub 2010 Jun 30.
citation: Elstrand MB, Sandstad B, Oksefjell H, Davidson B, Trope CG. Prognostic significance of residual tumor in patients with epithelial ovarian carcinoma stage IV in a 20 year perspective. Acta Obstet Gynecol Scand. 2012 Mar;91(3):308-17. doi: 10.1111/j.1600-0412.2011.01316.x. Epub 2012 Jan 9.
citation: Pomel C, Akladios C, Lambaudie E, Rouzier R, Ferron G, Lecuru F, Classe JM, Fourchotte V, Paillocher N, Wattiez A, Montoriol PF, Thivat E, Beguinot M, Canis M. Laparoscopic management of advanced epithelial ovarian cancer after neoadjuvant chemotherapy: a phase II prospective multicenter non-randomized trial (the CILOVE study). Int J Gynecol Cancer. 2021 Dec;31(12):1572-1578. doi: 10.1136/ijgc-2021-002888. Epub 2021 Oct 20.
citation: Fagotti A, Gueli Alletti S, Corrado G, Cola E, Vizza E, Vieira M, Andrade CE, Tsunoda A, Favero G, Zapardiel I, Pasciuto T, Scambia G. The INTERNATIONAL MISSION study: minimally invasive surgery in ovarian neoplasms after neoadjuvant chemotherapy. Int J Gynecol Cancer. 2019 Jan;29(1):5-9. doi: 10.1136/ijgc-2018-000012.