Clinical trial NCT00614211: Laparoscopic Approach to Cervical Cancer
Official title: A Phase III Randomized Clinical Trial of Laparoscopic or Robotic Radical Hysterectomy Versus Abdominal Radical Hysterectomy in Patients With Early Stage Cervical Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cervical Cancer
Keywords: Cervix
Cervical
Cancer
Carcinoma
Radical hysterectomy
Hysterectomy
Laparoscopy
Laparoscopic
Robotic
Squamous Cell
Adenosquamous
Adenocarcinoma
Lymphatic Mapping
IOLM
SPECT
Sentinel Node
Uterine cervix
Lead sponsor: Queensland Centre for Gynaecological Cancer
Sponsor class: OTHER_GOV
Collaborators: name: M.D. Anderson Cancer Center
First posted: 2008-02-13
Enrollment: 636
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical research study is to compare the long-term outcomes of different surgical methods for the treatment of cervical cancer. The long-term outcome of a total abdominal radical hysterectomy (TARH) will be compared against laparoscopy. In this study, the laparoscopy will be done with or without robotic technology.

Detailed description: Primary Objective:

To compare disease-free survival amongst patients who undergo a total laparoscopic (TLRH) or robotic radical hysterectomy (TRRH) verses those who undergo a total abdominal radical hysterectomy (TARH) for early stage cervical cancer.

Secondary Objectives:

* Compare patterns of recurrence between arms.
* Compare treatment-associated morbidity within 6 months from surgery.
* Compare the cost effectiveness of TLRH/TRRH versus TARH
* Compare the impact on Quality of Life (QOL) between arms.
* Assess pelvic floor function
* Compare overall survival between arms
* Determine the feasibility of sentinel lymph node biopsy in this group of patients

RATIONALE FOR STUDY DESIGN Total abdominal radical hysterectomy (TARH) and pelvic lymph node dissection (± aortic lymph node dissection ± postoperative \[chemo-\] radiotherapy) is the current standard treatment for early cervical cancer. While this is an accepted effective treatment, a laparotomy is highly invasive, visibly scarring and is associated with tissue trauma, blood loss and a significant risk of wound and infectious adverse events . Additionally, radical hysterectomy by laparotomy is associated with an average hospital stay of approximately 5 to 7 days and an average recovery period (from surgery) of 5 to 6 weeks.

Laparoscopic techniques have been demonstrated to be feasible and safe with previous retrospective studies on TLH showing encouraging results . In a number of retrospective and prospective, non-controlled series the incidence of treatment-related morbidity was less in patients who had a laparoscopic hysterectomy compared to patients who underwent a TAH . Retrospective data suggest that the recurrence rate and patterns of recurrence are similar in patients who had a laparoscopic or an open approach .

Treatment recommendations ideally are based on prospective, randomized trials comparing the current standard technique (TARH) with the proposed better technique (TLRH). However, there are currently no prospective studies available which directly compare TLRH against the standard treatment of TARH in regards to disease-free or overall survival.

The proposed clinical trial will be biphasic. The primary outcome variable in stage 1 will be feasibility of recruitment as determined by overall trial recruitment. Following completion of Stage 1, the data of this study will become the basis for assessing recurrence and disease-free survival in the Stage 2 design.

RATIONALE FOR THE QUALITY OF LIFE Retrospective studies suggest equivalency between the laparoscopic and open approaches to radical hysterectomy in regards to surgical specimens obtained and likely disease-free and overall survivals . Thus, quality of life could be seen as one of the most significant factors in recommending one approach over the other and therefore an extremely important endpoint for this protocol. In the GOG LAP-2 protocol , a trial evaluating a comparison between hysterectomy by laparotomy or laparoscopy, the investigators found equivalency adequacy of the two surgical approaches however a significant difference in short term quality of life favoring laparoscopy. As expected, patients who underwent laparoscopy had a faster return to baseline functioning compared with those patients who had undergone laparotomy which translated into improved short-term quality of life. By 6 months, however, patients in both cohorts were reporting equivalent quality of life parameters. Quality of life surveys employed with this Phase III clinical trial will encompass important endpoints such as postoperative pain and related symptoms using the MD Anderson Symptom Assessment Index (MDSAI), as well as cancer specific Functional Assessment of Cancer Therapy (FACT-Cx) and the general 12-Item Short-Form Health Survey (SF-12).

RATIONALE FOR LYMPHATIC MAPPING Published experience with the techniques for lymphatic mapping and sentinel lymph node detection in women with cervical cancer has been very limited. To date, no single study has enrolled more than 100 patients undergoing lymphatic mapping as part of their surgical treatment for cervical cancer. In fact, the majority of studies report on less than 50 patients. In addition, this procedure has not yet been shown to be viable in a multi-institutional setting. The limitations of previously published reports are important as these techniques are associated with a significantly high learning curve with early procedures less successful than later ones. This study will provide us the opportunity to enroll large numbers of patients for validation of intraoperative lymphatic mapping in women with cervical cancer in an international, multi-institutional setting.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed primary adenocarcinoma, squamous cell carcinoma or adenosquamous carcinoma of the uterine cervix;
* Patients with Histologically confirmed stage IA1 (with lymph vascular invasion), stage IA2, or stage IB1 disease
* Patients undergoing either a Type II or III radical hysterectomy (Piver Classification)
* Patients with adequate bone marrow, renal and hepatic function:
* ECOG Performance Status of 0 or 1.
* Patient must be suitable candidates for surgery.
* Patients who have signed an approved Informed Consent
* Patients with a prior malignancy allowed if \> 5 years ago with no current evidence of disease
* Females, aged 18 years or older
* Negative serum pregnancy test within \<30 days of surgery in pre-menopausal women and women \< 2 years after the onset of menopause

Exclusion Criteria:

* Any histology other than adenocarcinoma, squamous cell carcinoma or adenosquamous carcinoma of the uterine cervix;
* Tumor size greater than 4 cm;
* FIGO stage II-IV;
* Patients with a history of pelvic or abdominal radiotherapy;
* Patients who are pregnant;
* Patients with contraindications to surgery;
* Patients with evidence of metastatic disease by conventional imaging studies, enlarged pelvic or aortic lymph nodes \> 2cm; or histologically positive lymph nodes
* Unfit for Surgery: serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator);
* Patients unable to withstand prolonged lithotomy and steep Trendelenburg position
* Patient compliance and geographic proximity that do not allow adequate follow-up

Primary outcomes:
measure: Disease free survival
timeFrame: 5 years from surgery
Secondary outcomes:
measure: Patterns of recurrence
timeFrame: 5 years from surgery
measure: Costs
timeFrame: 6 months from surgery
measure: Quality of life Questionnaires
timeFrame: 6 months from surgery
measure: Pelvic Floor Distress Inventory Questionnaire
timeFrame: 5 years from surgery
measure: Overall survival
timeFrame: 5 years from surgery
measure: Feasibility of sentinel lymph node biopsy
timeFrame: Intra-operatively
measure: Intra-operative, peri-operative, post-operative and long term treatment related morbidity
timeFrame: 6 months from surgery
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Greater Baltimore Medical Centre
state: Maryland
city: Las Vegas
country: United States
facility: Women's Cancer Centre Nevada
state: Nevada
city: New York
country: United States
facility: St Luke's - Roosevelt Hospital Center
state: New York
city: Oklahoma City
country: United States
facility: Peggy and Charles Stephenson Oklahoma Cancer Center
state: Oklahoma
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Cordoba
country: Argentina
facility: Misericordia Hospital
city: Auchenflower
country: Australia
facility: The Wesley Hospital
state: Queensland
city: Greenslopes
country: Australia
facility: Greenslopes Private Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Health Services
state: Queensland
city: Townsville
country: Australia
facility: The Townsville Hospital
state: Queensland
city: Subiaco
country: Australia
facility: Saint John of God
state: Western Australia
city: Curitiba
country: Brazil
facility: Erastus Gaertner Hospital
state: Parana
city: Morumbi
country: Brazil
facility: Albert Einstein Hospital
state: San Paulo
city: Bras
country: Brazil
facility: Instituto Brasileiro de Controlle do Cancer
state: Sao Paulo
city: Barretos
country: Brazil
facility: Barretos Cancer Hospital
state: SP
city: Pleven
country: Bulgaria
facility: University Hospital Pleven Center of Oncology Gynaecology
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Guangzhou
country: China
facility: The First Affilated Hospital of Sun Yat-Sen University
state: Guangdong
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affliated Hospital of Wenzhou Medical College
state: Zhejiang
city: Antioquia
country: Colombia
facility: Institito De Cancerologia Clinica Las Americas
state: Medellin
city: Lecco
country: Italy
facility: Alessandro Manzoni Hospital
state: Milan
city: Monza
country: Italy
facility: San Gerardo Hospital
state: Milan
city: Milan
country: Italy
facility: Catholic University of the Sacred Heart
state: Rome
city: Milan
country: Italy
facility: European Institute of Oncology
city: Goyang-si
country: Korea, Republic of
facility: Korea Cancer Hospital
state: Seoul
city: Ihwa-Dong
country: Korea, Republic of
facility: Seoul National University - Department of Obstetrics and Gynecology
state: Seoul
city: Seoul
country: Korea, Republic of
facility: ASAN Medical Center
city: Tlalpan
country: Mexico
facility: Instituto Nacional de Cencerologia
state: Mexico City
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedades Neoplasicas
state: Surquillo
city: Caguas
country: Puerto Rico
facility: Gyneco-Oncologico Hospital HIMA
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Pedro Ramirez, M.D.
role: STUDY_CHAIR
affiliation: Queensland Centre for Gynecological Cancer
name: Andreas Obermair, MD
role: STUDY_CHAIR
affiliation: M.D. Anderson Cancer Center
name: Michael Frumovitz, M.D.
role: STUDY_CHAIR
References:
citation: Obermair A, Gebski V, Frumovitz M, Soliman PT, Schmeler KM, Levenback C, Ramirez PT. A phase III randomized clinical trial comparing laparoscopic or robotic radical hysterectomy with abdominal radical hysterectomy in patients with early stage cervical cancer. J Minim Invasive Gynecol. 2008 Sep-Oct;15(5):584-8. doi: 10.1016/j.jmig.2008.06.013.
citation: Tanaka T, Ueda S, Miyamoto S, Hashida S, Terada S, Konishi H, Kogata Y, Taniguchi K, Komura K, Ohmichi M. Comparison of Prognosis between Minimally Invasive and Abdominal Radical Hysterectomy for Patients with Early-Stage Cervical Cancer. Curr Oncol. 2022 Mar 24;29(4):2272-2283. doi: 10.3390/curroncol29040185.
citation: Frumovitz M, Obermair A, Coleman RL, Pareja R, Lopez A, Ribero R, Isla D, Rendon G, Bernardini MQ, Buda A, Moretti-Marquez R, Zevallos A, Vieira MA, Zhu T, Land RP, Nicklin J, Asher R, Robledo KP, Gebski V, Ramirez PT. Quality of life in patients with cervical cancer after open versus minimally invasive radical hysterectomy (LACC): a secondary outcome of a multicentre, randomised, open-label, phase 3, non-inferiority trial. Lancet Oncol. 2020 Jun;21(6):851-860. doi: 10.1016/S1470-2045(20)30081-4.
citation: Ramirez PT, Frumovitz M, Pareja R, Lopez A, Vieira M, Ribeiro R, Buda A, Yan X, Shuzhong Y, Chetty N, Isla D, Tamura M, Zhu T, Robledo KP, Gebski V, Asher R, Behan V, Nicklin JL, Coleman RL, Obermair A. Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer. N Engl J Med. 2018 Nov 15;379(20):1895-1904. doi: 10.1056/NEJMoa1806395. Epub 2018 Oct 31.