Clinical trial NCT01724944: LYmphadenectomy After NeoAdjuvant Chemotherapy
Official title: Lymphadenectomy After Neo-Adjuvant Chemotherapy in Ovarian Neoplasm
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Advanced Ovarian Cancer (Stage III or IV) After Neoadjuvant Chemotherapy
Keywords: Interval debulking surgery
IDS
NACT
Neoadjuvant chemotherapy
Lymphadenectomy
Ovarian cancer
Lead sponsor: Catholic University of the Sacred Heart
Sponsor class: OTHER
First posted: 2012-11-12
Enrollment: 65
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the role of lymphadenectomy in advenced ovarian cancer patients at the time of interval debulking surgery after neoadjuvant chemiotherapy.

Moreover it is a prospective trial, aimed to investigate the prognostic role of sistematic lymphadenectomy in terms of percentage of micrometastases detected, morbidity (complications rate), progression free interval, overall survival, recurrence pattern.

Detailed description: In patients with advanced ovarian cancer (FIGO stage III-IV), a percentage between 50% and 80% had lymph node metastases at diagnosis, mainly in para-aorto-caval (48 %) and iliac areas (49%). In 1988, FIGO has included lymph node metastasis in stage IIIC, although some authors argue that only node involvement constitutes a clinical course different from IIIC cancer patients with abdominal diffusion.

Although it has been demonstrated that lymphadenectomy is technically feasible and relatively safe in this subset of patients, however, it is burdened by a certain percentage of complications including limphocyst, lymphedema, hemorrhage, ranging from 6% to 45%. In addition, the actual therapeutic role is still controversial and it is not clear whether this surgical procedure should be part of the staging of these tumors. Retrospective studies have shown a benefit on overall survival in patients with ovarian cancer who underwent lymphadenectomy associated with optimal debulking (residual tumor \<1 cm). In a recent publication by SEER is found that the number of lymph nodes removed during surgery for advanced ovarian cancer is an independent prognostic factor.

In the literature there is only one prospective randomized study on lymphadenectomy in advanced ovarian cancer without node lesions macroscopically observed (bulky nodes) during the first surgery. The authors reported a significant benefit in terms of disease free survival (DFS), but not in terms of overall survival (OS) in patients who underwent systematic lymphadenectomy and who had a residual tumor \<1 cm. Patients with intra-abdominal residual tumor \<1 cm could theoretically not benefit from a systematic lymphadenectomy since most of lymph node metastases undetectable to intraoperative assessment are smaller than 1 cm.

About 20% of ovarian cancer patients stage III-IV, however, are not operable at the time of diagnosis because of the spread of the disease. In these cases, the gold standard treatment consists of submitting the patient to Interval Debulking Surgery (IDS) after neoadjuvant chemotherapy. The prognosis of these patients compared to those who are subjected to primary surgery, with the same residual tumor after surgery, is currently a topic of controversial debate. Recently, a multicenter, randomized EORTC showed no difference in prognosis between primary surgery and Interval Debulking Surgery in a population stratified by residual tumor. There are few retrospective studies that consider the presence of lymph node metastases in patients undergoing Interval Debulking Surgery: the percentage of lymph node metastases in this subset varies from 37.5% to 75%.

The purpose of the study is to assess whether systematic pelvic and aortic lymphadenectomy should be part of standard surgical procedures in patients with ovarian cancer who underwent surgery after neoadjuvant chemotherapy with intra-abdominal residual tumor \<1 cm.

All patients candidate for Interval Debulking Surgery which do not present bulky nodes at surgery and which have an intra-abdominal residual tumor \<1 cm at the end of the surgery will be enrolled in the study.

The baseline assessment of patients is to perform general blood tests, CA 125, CT thorax, abdomen, pelvis, anesthetic assessment and, if eligible, the patients will be subjected to the treatment above.

The enrollment period will last for 2 years until the achieving of 65 patients as the study population. The median follow-up of 6 months for all patients for the primary objectives and a median of 36 months for the secondary objectives.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 75 years
* Patients affected by advanced ovarian cancer (FIGO stage III-IV) who underwent \> 2 to \<7 cycles of neoadjuvant chemotherapy based on platinum and taxanes.
* Clinical response (instrumental and serological) complete or partial.
* Residual intra-abdominal tumor \<1 cm.
* Absence of disease macroscopically evident in lymph nodes (\> 1 cm)
* Life expectancy of at least 4 weeks
* ECOG PS ≤ 2
* Adequate respiratory function, hepatic, cardiac, bone marrow and renal function (creatinine clearance\> 60 mL / min according to the Cockroft formula)
* Patient psychologically able to follow the study procedures

Exclusion Criteria:

* Patients with severe impairment of lung function, or liver failure, such as not to allow access in safety in the operating room.
* Not epithelial ovarian neoplasms or borderline tumors
* Other invasive cancer in the last 5 years or signs of recurrence or activity
* Patients with intra-abdominal residual tumor\> 1 cm
* Patients with the presence of bulky nodes (\> 1 cm) in the intra-operative evaluation
* Diseases of the lymphatic system (including lymphatic edema of unknown origin)

Primary outcomes:
measure: Percentage of positive lymph nodes after neoadjuvant chemotherapy
timeFrame: 6 months
measure: Evaluation of complications related to the surgical procedure
timeFrame: 6 months
Secondary outcomes:
measure: Evaluation of disease-free interval (DFS)
timeFrame: 36 months
measure: Assessment of overall survival (OS)
timeFrame: 36 months
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Catholic University of Sacred Heart
Study officials:
References: