ULTRA-LAP Trial: Laparoscopic Debulking Surgery (LDS) in Advanced Ovarian Cancer (ULTRA-LAP)

• ClinicalTrials.gov Identifier: NCT05862740
• Recruitment Status: Recruiting
• Last Update Posted: May 17, 2023
• Sponsor: Azienda Ospedaliera di Padova
• Collaborator: University of Padova
• Information provided by (Responsible Party): Roberto Tozzi, Azienda Ospedaliera di Padova

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer	Procedure: Laparoscopic Debulking Surgery in advanced ovarian cancer; Procedure: Standard laparotomic Debulking Surgery in advanced ovarian cancer	Not Applicable

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.

Study Design

• Study Type: Interventional
• Estimated Enrollment: 62 participants
• Allocation: Non-Randomized
• Intervention Model: Factorial Assignment
• 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
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: ULTRA-LAP Trial: Laparoscopic Debulking Surgery (LDS) in Advanced Ovarian Cancer: a Feasibility Prospective Study
• Actual Study Start Date: January 2, 2022
• Estimated Primary Completion Date: December 31, 2026
• Estimated Study Completion Date: December 31, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Laparoscopic debulking surgery - LDS; Primary debulking surgery or Interval debulking surgery performed by laparoscopy (P-LDS and I-LDS)	Procedure: Laparoscopic Debulking Surgery in advanced ovarian cancer; Laparoscopic debulking will be conducted until the surgical target is achieved or the operation is converted to laparotomy.
Active Comparator: Debulking surgery - DS; Primary debulking surgery or Interval debulking surgery performed by/converted to laparotomy (PDS and IDS)	Procedure: Standard laparotomic Debulking Surgery in advanced ovarian cancer; Debulking by laparotomy in patients when debulking could not be accomplished by laparoscopy.

Outcome Measures

Primary Outcome Measures :

1. Safety: rate of complications/morbidities [ Time Frame: 60 days ]
   Safety will be measured as the rate of patients experiencing intra- and post-operative early and late morbidities (within and after the hospitalization up to 60 days from surgery) and it will be compared to the morbidity rate of patients having similar surgery by laparotomy. Complications are going to be graded according to Clavien-Dindo classification.
2. Efficacy: rate of complete resection (CR) in group 1 [ Time Frame: 60 days ]
   Efficacy will be measured as the rate of patients in which the surgical target set pre-operatively is achieved by laparoscopy.
3. Feasibility: rate of procedures completed by laparoscopy [ Time Frame: 60 days ]
   Feasibility will be measured as the rate of patients who have their procedure completed by laparoscopy.

Secondary Outcome Measures :

1. Progression Free Survival (PFS). [ Time Frame: 5 years ]
   the time interval from the surgical treatment to the date of the documented first recurrence of disease, by CA 125 (Carbohydrate Antigen 125) and/or CT scan.
2. Overall Survival (OS). [ Time Frame: 5 years ]
   time between surgery and death.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Matteo Marchetti, Doctor; 0039-049-8213445; matteomarchetti91@gmail.com

Contact: Marco Noventa, Doctor; 0039-049-8213445; marco.noventa@gmail.com

Locations

Italy

Azienda Ospedaliera Universitaria di Padova,; Recruiting

Padova, Padova, Veneto, Italy, 35128

Contact: Matteo Marchetti, MD matteomarchetti91@gmail.com

Contact: Marco Noventa, MD marco.noventa@gmail.com

Sub-Investigator: Carlo Saccardi, Professor

Sub-Investigator: Marco Noventa, MD

Sub-Investigator: Matteo Marchetti, MD

Sponsors and Collaborators

Azienda Ospedaliera di Padova

University of Padova

Investigators

• Principal Investigator: Roberto Tozzi, Professor; Azienda Ospedale Università di Padova

More Information

Publications of Results:

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.

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.

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.

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.

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.

• Responsible Party: Roberto Tozzi, Professor and Chair, Azienda Ospedaliera di Padova
• ClinicalTrials.gov Identifier: NCT05862740
• Other Study ID Numbers: 5497/AO/22; AOP2674 ( Other Identifier: University of Padova )
• First Posted: May 17, 2023
• Last Update Posted: May 17, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Roberto Tozzi, Azienda Ospedaliera di Padova:

Ovarian cancer; Advanced ovarian cancer; Debulking surgery; Multivisceral surgery; Laparoscopic debulking surgery

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type