Surgical Complications Related to Primary or Interval Debulking in Ovarian Neoplasm

Study Overview
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Brief Summary
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Patients with advanced ovarian cancer (FIGO stage III C) and highly disseminated tumor will be randomized into two arms: primary debulking surgery followed by adjuvant chemotherapy vs. neoadjuvant chemotherapy followed by interval debulking surgery (IDS). The primary end point is the evaluation and comparison of the surgical complications of primary surgery and IDS and the evaluation of the progression free survival (PFS)

Official Title
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Surgical Complications Related to Primary or Interval Debulking in Ovarian Neoplasm

Conditions
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Stage IIIC Ovarian Cancer

Intervention / Treatment
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* Drug: Neoadjuvant chemotherapy + Interval Debulking Surgery
* Procedure: Primary Debulking Surgery + Adjuvant Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with suspected advanced ovarian cancer (FIGO stage IIIC) PIV ≥ 8, PIV ≤ 12 Estimated life expectancy of at least 4 weeks. PS ≤ 2 Appropriate respiratory, hepatic, cardiological, bone marrow and renal functions (Creatinine Clearance > 60 mL/min according to Cockcroft formula) Patient capable of consent. Exclusion Criteria: Pregnancy or breastfeeding. Non-appropriate respiratory, hepatic, cardiological, bone marrow and renal functions Large size mass reaching the xiphoid, occupying all the abdominal cavity and/or infiltrating the abdominal wall. Mesenteric retraction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomly assigned (1:1 ratio) to undergo either PDS followed by systemic adjuvant chemotherapy, or NACT followed by IDS. Random assignment will be centralised at the Institutional clinical trial center using a block-randomisation computer-generated list (maximum allowable percentage deviation = 10%). Allocation will be concealed to patients and investigators. Patients and investigators will not be masked to group assignment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Primary debulking surgery<br>All patients with suspicion of advanced ovarian carcinoma (FIGO stage IIIC) will undergo to a diagnostic laparoscopy in order to obtain a laparoscopic score (PIV) based on seven parameters: omental cake, peritoneal and diaphragmatic extensive carcinosis, mesenteric retraction, bowel and stomach infiltration, spleen and/or liver superficial metastasis, as previously published (Fagotti et al, American Journal of Obstetrics and Gynecology, 2008) Patients with PIV ≥ 8 and ≤ 12 randomized in this group will be submitted to an attempt of primary debulking surgery in order to obtain RT < 1 cm, followed by adjuvant chemotherapy. | Procedure: Primary Debulking Surgery + Adjuvant Chemotherapy<br>* Patients with suspected advanced ovarian cancer (FIGO stage IIIC) will undergo to diagnostic laparoscopy. Omental cake, diaphragmatic or peritoneal extensive carcinomatosis, tumor diffusion to the small and large curvature of the stomach, large and/or small bowel mesentery disease, spleen and/or liver metastases will be investigated in order to obtain a laparoscopic score. Then, an attempt of laparotomic cytoreduction will be performed: total hysterectomy, bilateral salpingo-oophorectomy, radical omentectomy, appendectomy, pelvic and paraaortic lymphadenectomy, eventual bowel resection, eventual bladder resection, eventual splenectomy, eventual parietal and diaphragmatic peritonectomy, eventual gastric resection, eventual hepatic resection, eventual pancreas resection, eventual cholecystectomy.<br>|
| Experimental: Interval debulking surgery<br>All patients with suspicion of advanced ovarian carcinoma (FIGO stage IIIC) will undergo to a diagnostic laparoscopy in order to obtain a laparoscopic score (PIV) based on seven parameters: omental cake, peritoneal and diaphragmatic extensive carcinosis, mesenteric retraction, bowel and stomach infiltration, spleen and/or liver superficial metastasis, as previously published (Fagotti et al, American Journal of Obstetrics and Gynecology, 2008) Patients with PIV ≥ 8 and ≤ 12 randomized in this group will be submitted only to diagnostic laparoscopy followed by neoadjuvant chemotherapy and subsequent Interval Debulking Surgery, followed by further cycles of chemotherapy. | Drug: Neoadjuvant chemotherapy + Interval Debulking Surgery<br>* Patients with suspected advanced ovarian cancer (FIGO stage IIIC) will undergo only to diagnostic laparoscopy. Omental cake, diaphragmatic or peritoneal extensive carcinomatosis, tumor diffusion to the small and large curvature of the stomach, large and/or small bowel mesentery disease, spleen and/or liver metastases will be investigated in order to obtain a laparoscopic score. After neoadjuvant chemotherapy interval debulking surgery will be performed: total hysterectomy, bilateral salpingo-oophorectomy, radical omentectomy, appendectomy, pelvic and paraaortic lymphadenectomy, eventual bowel resection, eventual bladder resection, eventual splenectomy, eventual parietal and diaphragmatic peritonectomy, eventual gastric resection, eventual hepatic resection, eventual pancreas resection, eventual cholecystectomy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation and comparison of early surgical complications of primary surgery and Interval debulking surgery. | Early surgical complications: Blood transfusion Re-laparotomy suture dehiscence of laparotomy. Venous thrombosis Haemorrhage Death in the post-operative period Digestive fistula Urinary fistula Lymphocyst Fever Infection Pleural effusion Pulmonary embolism Pneumothorax Pneumonia | thirty days | 
| Evaluation and comparison of late surgical complications of primary surgery and Interval debulking surgery | Late surgical complication: Death for every reason. Suture dehiscence of laparotomy with opening of the abdominal muscles Fever due to lymphocystis infection | six months | 
| Evaluation of the progression free survival (PFS) | Time from randomization until recurrence of tumor or death from any cause. | Thirty-six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Time from randomization until death from any cause. | Thirty-six months | 
| Evaluation of Quality of life | Quality of life will be assess using the EORTC quality of life questionnaire core-36 (QLQC-30) and the ovarian cancer-specific quality of life questionnaire (QLQ-Ov28). These will be complete at study entry, at the 4th cycle or before IDS (in arm A and arm B, respectively), at the 6th cycle, and 6 months after the last cycle of chemotherapy. | 12 months |