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Trial Title:
TMMR (Total Mesometrial Resection) Register Study
NCT ID:
NCT01819077
Condition:
Cervical Cancer
Conditions: Official terms:
Uterine Cervical Neoplasms
Conditions: Keywords:
Cervical cancer
TMMR
therapeutic lymphadenectomy
register study
Study type:
Observational [Patient Registry]
Overall status:
Unknown status
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Procedure
Intervention name:
TMMR
Description:
Radical hysterectomy by Total Mesometrial Resection (TMMR) and therapeutic
lymphadenectomy (tLNE)
Arm group label:
TMMR
Summary:
TMMR/tLNE was shown to result in very low locoregional recurrence rates and low morbidity
in surgical treatment of cervical cancer stage IB-IIA without any adjuvant radiotherapy
even in high risk situations. More and more this therapeutic strategy is implemented in
clinical routine in specialized cancer centres, thus, treatment of cervical cancer could
be performed for these stages in a systematically defined and reproducible radicality;
adjuvant radiotherapy could be spared for recurrent disease, thus lowering morbidity and
resource assignment in primary treatment dramatically. Due to the nerve-sparing character
of the procedure bladder, bowel and sexual dysfunction would also be minimized and
markedly benefit the patient.
This study is designed to follow up the results of this therapeutic concept adapted to
clinical routine in a multiinstitutional register study accompanied by detailed
assessment of pathological work-up, quality of life and bladder and sexual function
following surgery.
Detailed description:
Rationale for the multimodal treatment of cervical cancer in FIGO stages IB-IIA according
to M. Hoeckel: Total mesometrial resection (TMMR) is a newly developed procedure for
surgical treatment of cervical cancer of FIGO stage IB to IIB. The procedure is based on
embryologically determined surgical anatomy that was generated from investigations of the
embryonal and fetal development of the Müllerian organ system and of local tumor spread
of cervical cancer at the macroscopic, microscopic and molecular level (11-13). The
observation that the cervical cancer follows the embryologically derived compartment
hierarchy led to the definition of a new principle of radicality for oncological surgery,
i.e., the resection of a tumor within the borders of the compartment representing the
morphogenetic unit of the tumor origin. A resection that follows this principle leads to
high local control (>95%) without additional radiotherapy. The resection line of the
vagina is located inside the compartment, therefore intraoperative frozen section
examination of the TMMR specimen is necessary to achieve wide margins. Adjacent
structures that belong to another morphogenetic unit can be saved in spite of immediate
proximity to the tumor. The autonomic nerves are saved with the TMMR concept as well as
the ureters, the urinary bladder and their mesenteries containing all blood vessels, and
the rectum with the mesorectum.
Therapeutic LNE: With TMMR tLNE has to be done with therapeutic intent, so that in case
of lymph node metastases a high regional tumor control without adjuvant radiotherapy can
be achieved (27). Therapeutic pelvic tLNE needs the removal of the lymph node groups
within the scope of the classical systematic pelvic LNE and additionally, the
paravisceral fatty tissue inferior to the obturator nerve, perispinal, gluteal and
presacral lymph nodes to S2. The therapeutic pelvic LNE is done with exposition and
protection of the plexus hypogastricus superior, the nervus hypogastricus and the plexus
hypogastricus inferior and all ureter supplying vessels, bilaterally. In case of
intraoperative evidence of pelvic lymph node metastases in first line nodes stepwise
ascending therapeutic para-aortic LND with protection of the plexus hypogastricus
superior and the nervi splanchnici lumbales has to be done. To date no prospective,
randomized trial has proven a survival benefit of adjuvant chemotherapy alone in patients
with early cervical cancer and histopathological risk factors. However, retrospective
studies and the results of Peters et al. (20), comparing adjuvant chemo-radiotherapy with
radiotherapy alone in patients after surgery for cervical cancer suggest that adjuvant
chemotherapy may exert an impact on survival. The possible effect of adjuvant
chemotherapy should be taken into consideration when applying only surgical therapeutic
concepts (23;25). Therefore, adjuvant chemotherapy in case of risk factors was performed
Hoeckel's trial. The mono-institutional prospective study of the University of Leipzig,
Department of Gynecology and Obstetrics, has shown that the treatment concept for
cervical cancer FIGO stages IB-IIB including TMMR and therapeutic LNE without adjuvant
radiotherapy achieves a markedly improved therapeutic index in comparison with historic
controls (16;22): locoregional control was 96% versus 91%, relapse-free survival after
three years was 93% vs. 84%, treatment-caused side effects were 9% exclusively grade II
vs. 28% grade II and III (11-13).
Scientific aims
1. Observation of results of standardization of radical hysterectomy and therapeutic
lymphadenectomy in cervical cancer FIGO IB -IIA on the basis of ontogenetically
defined compartment theory in a multicentric approach by TMMR/LND in clinical
routine
2. Assessment of locoregional recurrence in this concept without any radiation therapy
showing that postoperative irradiation and associated morbidity can also be avoided
and irradiation may be maintained for rescue in recurrency under conditions of
clinical routine
3. Confirmation of the low morbidity of TMMR due to autonomous nerve and vessel
preservation by concomitant urogynecological and psychosexual subprotocols in
clinical routine treatment
Requirements for participating centers of the register study
1. Study of educational video (M. Hoeckel, Leipzig 2010; R. Kimmig, Essen 2012)
2. Passed Participation of 2 day educational training concerning TMMR at "Leipzig
School of Oncological Surgery"
3. Performing at least 10 TMMR procedures at participating institution/year
4. Evaluation of surgical technique at the participating institution by Prof. Hoeckel
(Leipzig) or Prof. Kimmig (Essen) or substitute determined by M.Hoeckel or R. Kimmig
5. Securing standardized workup of the surgical specimen by pathologists according to
the protocol (Prof. Horn, Leipzig)
6. Acceptance of study participation by the responsible project leader and commitment
of online documentation of primary histopathological and clinical data as well as
follow up data when assessed.
Primary outcome measures:
(1) Progression-free survival, defined as time from TMMR to a local or regional relapse,
of a distant metastasis or to death of any cause whichever event comes first.
Simultaneous occurrence of pelvic and distant metastases is considered as distant but
should be documented in detail.
Secondary efficacy measures:
1. Overall survival, defined as time from TMMR to death of any cause; Rate of
locoregional relapse and rate of distant metastases at 3 years.
2. Postoperative dysfunction of the bladder/urethra and of psychosexual function,
assessed as described in the urogynecological and psychosexual subprotocol.
Secondary safety measures:
1. Therapy-induced morbidity on bladder/urethra, rectum/bowel, vagina/vulva, assessed
by the LENT-SOMA scoring system at the following times after surgery: subjective
scale on day 1, week 1 and 2, month 3; subjective and objective scale on month 12
and 24. The questionnaires developed by Davidson (7) will be used; Time from surgery
to first micturition; Acute complications of surgery; adverse and serious adverse
events.
2. Quality of life by EORTC-QLQ-C30 questionnaire at 12 and 24 months after surgery.
Aim of the study is to assess recurrence rate and morbidity following TMMR/LNE without
additional radiotherapy in a multicentric observation of clinical routine treatment. In
addition standardization of radical hysterectomy and of pathological work up for stage Ib
to IIa cervical cancer will be achieved as described in "Requirements of participating
centers". Two primary endpoints will be investigated, ranked according to their
relevance: (1) PFS and (2) Late effects on bladder/urethra, measured by the subjective
scale of the LENT-SOMA system. A hierarchical strategy will be used.
Further time to event endpoints will be illustrated by Kaplan-Meier plots and analyzed
like the primary endpoint see above.
Criteria for eligibility:
Study pop:
Patients with cervical cancer Stages IB - IIA treated with TMMR and tLNE.
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
- Histologically proven cervical cancer: squamous cell carcinoma or adenocarcinoma;
FIGO stages IB - IIA (preoperatively); Karnofsky-Index ≥ 70; unrestricted
operability; BMI <35; age >=18 years.
- Individual decision for treatment of TMMR and therapeutic LNE without adjuvant
radiotherapy by the responsible clinic (clinician) on a clinical routine basis.
- Informed consent of the patient
Exclusion criteria:
- Neuroendocrine differentiation and all preoperative FIGO stage IA or >IIA;
- Distant metastases except in para-aortic lymph nodes; sclerodermia, lupus
erythematodes, mixed connective tissue disease; secondary malignancy; previous
radiotherapy of the pelvis.
- Patients with diseases of the connective tissue will be excluded because of
unforeseeable (e.g. neurological) symptoms and disorders after surgery. Patients
with a BMI ≥ 35 will be excluded because of very high risks regarding wound healing,
infections and thrombosis independent on the type of surgery.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University Hospital Essen
Address:
City:
Essen
Zip:
45122
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Rainer Kimmig, Prof. Dr.
Phone:
00492017232241
Email:
rainer.kimmig@uk-essen.de
Contact backup:
Last name:
Paul Buderath, Dr.
Phone:
004920172385293
Email:
paul.buderath@uk-essen.de
Investigator:
Last name:
Rainer Kimmig, Prof. Dr.
Email:
Principal Investigator
Investigator:
Last name:
Paul Buderath, Dr.
Email:
Principal Investigator
Start date:
March 2013
Completion date:
March 2018
Lead sponsor:
Agency:
University Hospital, Essen
Agency class:
Other
Source:
University Hospital, Essen
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT01819077