Diaphragmatic Resection And Gynecological Ovarian Neoplasm

NCT ID: NCT03543462

Last Updated: 2020-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-20
• Study Completion Date: 2020-01-11

Brief Summary

Prospective randomized phase IV study aimed to value the impact of diaphragmatic surgery and the useful of intra-operatory thoracic drain in advanced ovarian cancer.

Considering the fact that the diaphragmatic surgery could contribute with the incidence of post-operatory morbidity. The study is aimed to value the role of thoracic drain in post-operative outcomes as hospital stay, time to chemotherapy, drugs use and eventual interventions.

Detailed Description

Ovarian cancer represents the leading cause of death from gynecologic malignancies. The majority of patients present with advanced-stage disease (III/IV) often involving the upper abdomen. Spread by either direct extension or via peritoneal implantation can result in metastases to the diaphragm, as seen in up to 40% of patients with advanced disease.

Standard treatment of advanced-stage disease includes primary cytoreductive surgery followed by combination platinum-taxane chemotherapy. Optimal cytoreduction to ≤1 cm disease has repeatedly been shown to be associated with improved survival.

Diaphragm involvement was considered one of the most frequent obstacles to achieving optimal cytoreduction. The right diaphragm is more frequently and extensively involved than the left diaphragm; however, bilateral involvement is not uncommon. Various studies have advocated and reported the feasibility of diaphragmatic surgery in achieving optimal cytoreduction.

Sometimes, depending on extent of the disease, the diaphragm involvement could be massive and often the resection of the muscle with access to pleural cavity is necessary. Allegedly, entering the pleural cavity increases the morbidity of the procedure.

Extensive upper abdominal surgery involving diaphragmatic peritonectomy/resection and liver mobilization may both contribute to the development of symptomatic pleural effusions.

The aim of the study is to value the impact of diaphragmatic surgery in post-operative complications using a specific score (DRS). The other aim is to asses a correct management of intra-operatory thoracic drain position after diaphragmatic surgery. All parameter that could influence the post-operative outcomes as (EBL,BMI, OT, SCS) are recorded.

The study was approved by Ethical Committee of Fondazione Policlinico Gemelli Hospital (prot n. 9078/18).

The study is a superiority randomized clinical trial to investigate the role of intra-operative chest tube in the large (> 5 cm) diaphragmatic peritonectomy/resection in the ovarian cancer debulking. Calculation of sample size for the analysis of the primary end-point (major pleural effusion) was based on literature results reporting a rate of moderate/severe early peri-operative pleural effusion between 54% and 23% when a large (> 5 cm) diaphragmatic resection is performed. A sample size of 88 patients was required in order to provide 80% power of detecting a reduction of 60% of moderate/severe pleural effusion in PDS with large diaphragmatic resection when intra-operative chest tube was inserted (overall rate 22%) (two-tailed α =0.05, drop-out 5%).

Sample size is composed by 44 Patients affected by advanced stage ovarian cancer, meeting inclusion criteria, undergo diaphragmatic surgery followed by intra-operatory thoracic drain position and 44 patients with same characteristics undergo to diaphragmatic surgery without intra-operatory thoracic drain position. Both groups are compared in terms of incidence of post-operative complications (especially pleural effusion, pneumothorax, respiratory disease). Secondary endpoints are the evaluation of surgical outcomes and clinical outcomes in terms hospital stay, procedures and radiologic examinations required. All patients are adequately informed and inserted in the study only after having read and signed an informed consent. Diagnostic, clinical and surgical data of each patient are prospectively recorded.

Surgical procedures consist of surgical standard cytoreduction, performed for all cases of advanced stage ovarian cancer disease. The procedures performed depending on disease spread.

The diaphragmatic procedures, depending on the disease infiltration can consists of superficial peritonectomy, deep peritonectomy (until muscular layer) or diaphragmatic resection. Considering the randomization, if required, a thoracic drain tube 24 Fr. is positioned. A post-operative chest X-Ray is performed on all cases.

At the end of the procedure, a schedule is compiled with intraoperative data.

Post-operative examinations are follows:

• Chest X-Ray (2 h post-op)
• Chest X-Ray (day 1)
• Chest X-Ray (if required, depending of clinical indications)
• Thoracic US scan evaluation before discharge
• Thoracic US scan evaluation 10 days after discharge
• Radiological examinations (if required, depending of clinical indications)

All clinical and histologic data will be recorded prospectively using an electronic database.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Arm A: Chest tube positioning YES

Patients enrolled for chest tube positioning

Group Type: SHAM_COMPARATOR

thoracic Drain Tube 24 Fr.

Intervention Type: DEVICE

Positioning of Thoracic Drain after diaphragmatic resection and consequently diaphragmatic repair

Arm B: Chest tube positioning NO

Patients enrolled for diaphragm closure without chest tube positioning

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

thoracic Drain Tube 24 Fr.

Positioning of Thoracic Drain after diaphragmatic resection and consequently diaphragmatic repair

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Age > 18 < 80 years
• Patient's informed consent
• American Society of Anesthesiologists: < class III or IV
• No actual pregnancies or pelvic inflammatory disease (P.I.D.)
• BMI < 40
• Macroscopic diaphragmatic disease infiltration (mono lateral)
• Grade IIIA-IV diaphragmatic resection score
• Advanced stage ovarian cancer (stage III-IV)
• Primary diagnosis, interval debulking surgery, recurrent disease
• All histotype included

Exclusion Criteria

• Actual pregnancies or P.I.D
• BMI > 40
• Pulmonary or thoracic preoperatory disease
• Preoperative pleural effusion
• Residual thoracic disease after surgery
• Residual diaphragmatic disease after surgery

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Catholic University of the Sacred Heart

OTHER

Sponsor Role: lead

Responsible Party

Prof. Giovanni Scambia

Head of Department of Women's and Children's Health, Policlinico Agostino Gemelli Foundation University Hospital, Rome, Italy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stefano Cianci, M.D.

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico Agostino Gemelli

Locations

Fondazione Policlinico Agostino Gemelli

Roma, Rome, Italy

Countries

Italy

References

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013 Jan;63(1):11-30. doi: 10.3322/caac.21166. Epub 2013 Jan 17.

Reference Type: BACKGROUND

PMID: 23335087 (View on PubMed)

Eisenkop SM, Spirtos NM. What are the current surgical objectives, strategies, and technical capabilities of gynecologic oncologists treating advanced epithelial ovarian cancer? Gynecol Oncol. 2001 Sep;82(3):489-97. doi: 10.1006/gyno.2001.6312.

Reference Type: BACKGROUND

PMID: 11520145 (View on PubMed)

Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol. 2002 Mar 1;20(5):1248-59. doi: 10.1200/JCO.2002.20.5.1248.

Reference Type: BACKGROUND

PMID: 11870167 (View on PubMed)

Winter WE 3rd, Maxwell GL, Tian C, Carlson JW, Ozols RF, Rose PG, Markman M, Armstrong DK, Muggia F, McGuire WP; Gynecologic Oncology Group Study. Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Aug 20;25(24):3621-7. doi: 10.1200/JCO.2006.10.2517.

Reference Type: BACKGROUND

PMID: 17704411 (View on PubMed)

Aletti GD, Dowdy SC, Podratz KC, Cliby WA. Surgical treatment of diaphragm disease correlates with improved survival in optimally debulked advanced stage ovarian cancer. Gynecol Oncol. 2006 Feb;100(2):283-7. doi: 10.1016/j.ygyno.2005.08.027. Epub 2005 Sep 22.

Reference Type: BACKGROUND

PMID: 16182350 (View on PubMed)

Tsolakidis D, Amant F, Van Gorp T, Leunen K, Neven P, Vergote I. The role of diaphragmatic surgery during interval debulking after neoadjuvant chemotherapy: an analysis of 74 patients with advanced epithelial ovarian cancer. Int J Gynecol Cancer. 2010 May;20(4):542-51. doi: 10.1111/IGC.0b013e3181d4de23.

Reference Type: BACKGROUND

PMID: 20686373 (View on PubMed)

Zapardiel I, Peiretti M, Zanagnolo V, Biffi R, Bocciolone L, Landoni F, Aletti G, Colombo N, Maggioni A. Diaphragmatic surgery during primary cytoreduction for advanced ovarian cancer: peritoneal stripping versus diaphragmatic resection. Int J Gynecol Cancer. 2011 Dec;21(9):1698-703. doi: 10.1097/IGC.0b013e31822f65c3.

Reference Type: BACKGROUND

PMID: 22080893 (View on PubMed)

Fanfani F, Fagotti A, Gallotta V, Ercoli A, Pacelli F, Costantini B, Vizzielli G, Margariti PA, Garganese G, Scambia G. Upper abdominal surgery in advanced and recurrent ovarian cancer: role of diaphragmatic surgery. Gynecol Oncol. 2010 Mar;116(3):497-501. doi: 10.1016/j.ygyno.2009.11.023. Epub 2009 Dec 11.

Reference Type: BACKGROUND

PMID: 20004958 (View on PubMed)

Chereau E, Ballester M, Selle F, Cortez A, Pomel C, Darai E, Rouzier R. Pulmonary morbidity of diaphragmatic surgery for stage III/IV ovarian cancer. BJOG. 2009 Jul;116(8):1062-8. doi: 10.1111/j.1471-0528.2009.02214.x. Epub 2009 May 14.

Reference Type: BACKGROUND

PMID: 19459863 (View on PubMed)

Devolder K, Amant F, Neven P, van Gorp T, Leunen K, Vergote I. Role of diaphragmatic surgery in 69 patients with ovarian carcinoma. Int J Gynecol Cancer. 2008 Mar-Apr;18(2):363-8. doi: 10.1111/j.1525-1438.2007.01006.x.

Reference Type: BACKGROUND

PMID: 18334014 (View on PubMed)

Eisenhauer EL, D'Angelica MI, Abu-Rustum NR, Sonoda Y, Jarnagin WR, Barakat RR, Chi DS. Incidence and management of pleural effusions after diaphragm peritonectomy or resection for advanced mullerian cancer. Gynecol Oncol. 2006 Dec;103(3):871-7. doi: 10.1016/j.ygyno.2006.05.023. Epub 2006 Jul 3.

Reference Type: BACKGROUND

PMID: 16815536 (View on PubMed)

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.

Reference Type: BACKGROUND

PMID: 15273542 (View on PubMed)

Cliby W, Dowdy S, Feitoza SS, Gostout BS, Podratz KC. Diaphragm resection for ovarian cancer: technique and short-term complications. Gynecol Oncol. 2004 Sep;94(3):655-60. doi: 10.1016/j.ygyno.2004.04.032.

Reference Type: BACKGROUND

PMID: 15350355 (View on PubMed)

Other Identifiers

D.R.A.G.O.N. ID. 1963

Identifier Type: -

Identifier Source: org_study_id