LACC: Laparoscopic Approach to Cervical Cancer

Sponsor

Queensland Centre for Gynaecological Cancer (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00614211

Collaborator

M.D. Anderson Cancer Center (Other)

636

Enrollment

Locations

Arms

174

Anticipated Duration (Months)

19.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer	Procedure: Total Abdominal Radical Hysterectomy Procedure: Total Laparoscopic or Robotic Radical Hysterectomy	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

636 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 1, 2008

Actual Primary Completion Date :

Jan 1, 2022

Anticipated Study Completion Date :

Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Total Abdominal Radical Hysterectomy	Procedure: Total Abdominal Radical Hysterectomy In a radical hysterectomy the uterus, the upper one to two centimetres of the vagina and the soft tissues around the cervix are excised. Other Names: TARH Open radical hysterectomy
Experimental: 2 Total Laparoscopic or Robotic Radical Hysterectomy	Procedure: Total Laparoscopic or Robotic Radical Hysterectomy In a radical hysterectomy the uterus, the upper one to two centimetres of the vagina and the soft tissues around the cervix are excised. Other Names: TLRH TRRH Keyhole radical hysterectomy

Arm

Intervention/Treatment

Active Comparator: 1

Total Abdominal Radical Hysterectomy

Procedure: Total Abdominal Radical Hysterectomy

In a radical hysterectomy the uterus, the upper one to two centimetres of the vagina and the soft tissues around the cervix are excised.

Other Names:

TARH

Open radical hysterectomy

Experimental: 2

Total Laparoscopic or Robotic Radical Hysterectomy

Procedure: Total Laparoscopic or Robotic Radical Hysterectomy

In a radical hysterectomy the uterus, the upper one to two centimetres of the vagina and the soft tissues around the cervix are excised.

Other Names:

TLRH

TRRH

Keyhole radical hysterectomy

Outcome Measures

Primary Outcome Measures

Disease free survival [5 years from surgery]
Compare treatment equivalence

Secondary Outcome Measures

Patterns of recurrence [5 years from surgery]
date and localization of 1st recurrence as confirmed histologically - Compare patterns between groups
Costs [6 months from surgery]
Compare costs between groups
Quality of life Questionnaires [6 months from surgery]
Compare QoL between groups
Pelvic Floor Distress Inventory Questionnaire [5 years from surgery]
Compare PFDI between groups
Overall survival [5 years from surgery]
Compare between groups
Feasibility of sentinel lymph node biopsy [Intra-operatively]
Compare between groups
Intra-operative, peri-operative, post-operative and long term treatment related morbidity [6 months from surgery]
Compare these between groups

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Greater Baltimore Medical Centre	Baltimore	Maryland	United States	21204
2	Women's Cancer Centre Nevada	Las Vegas	Nevada	United States	89169
3	St Luke's - Roosevelt Hospital Center	New York	New York	United States	10019
4	Peggy and Charles Stephenson Oklahoma Cancer Center	Oklahoma City	Oklahoma	United States	73104
5	M.D. Anderson Cancer Center	Houston	Texas	United States	77230-1439
6	University of Wisconsin	Madison	Wisconsin	United States	53792
7	Misericordia Hospital	Cordoba		Argentina
8	The Wesley Hospital	Auchenflower	Queensland	Australia	4066
9	Greenslopes Private Hospital	Greenslopes	Queensland	Australia	4120
10	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
11	Mater Health Services	South Brisbane	Queensland	Australia	4101
12	The Townsville Hospital	Townsville	Queensland	Australia	4814
13	Saint John of God	Subiaco	Western Australia	Australia
14	Erastus Gaertner Hospital	Curitiba	Parana	Brazil
15	Albert Einstein Hospital	Morumbi	San Paulo	Brazil
16	Instituto Brasileiro de Controlle do Cancer	Bras	Sao Paulo	Brazil
17	Barretos Cancer Hospital	Barretos	SP	Brazil
18	University Hospital Pleven Center of Oncology Gynaecology	Pleven		Bulgaria	5800
19	Princess Margaret Hospital	Toronto	Ontario	Canada
20	The First Affilated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong	China
21	Zhejiang Cancer Hospital	Hangzhou	Zhejiang	China
22	The First Affliated Hospital of Wenzhou Medical College	Wenzhou	Zhejiang	China	325000
23	Institito De Cancerologia Clinica Las Americas	Antioquia	Medellin	Colombia
24	Alessandro Manzoni Hospital	Lecco	Milan	Italy
25	San Gerardo Hospital	Monza	Milan	Italy
26	Catholic University of the Sacred Heart	Milan	Rome	Italy
27	European Institute of Oncology	Milan		Italy	20141
28	Korea Cancer Hospital	Goyang-si	Seoul	Korea, Republic of
29	Seoul National University - Department of Obstetrics and Gynecology	Ihwa-Dong	Seoul	Korea, Republic of
30	ASAN Medical Center	Seoul		Korea, Republic of
31	Instituto Nacional de Cencerologia	Tlalpan	Mexico City	Mexico
32	Instituto Nacional de Enfermedades Neoplasicas	Lima	Surquillo	Peru
33	Gyneco-Oncologico Hospital HIMA	Caguas		Puerto Rico