Trial document





This trial has been registered retrospectively.
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  DRKS00015171

Trial Description

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Title

Novel surgical treatment approaches based on ontogenetic anatomy for vaginal and cervical cancer: TMMR, KMMR, EMMR, LEER and tLNE

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Trial Acronym

[---]*

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URL of the Trial

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Brief Summary in Lay Language

A novel surgical concept for the treatment of cervical and vaginal cancer has been developed at the Leipzig University Medical Center. In contrast to the traditional treatment approach, the tumor is not resected with a mere safety margin of healthy tissue but within its embryologically predefined compartment of potential tumor spread. In addition, all lymphatic tissue at risk for tumor involvement is removed during the operation. One major advantage of this treatment is the avoidance of postoperative radiotherapy which is omitted in all cases, leading to a reduction in treatment related complications. The goal of the ongoing study is to further evaluate the complications and the survival outcomes after the operation. Furthermore, pathologists will investigate the exact tumor spreading patterns in order to gain an even better understanding of the mechanisms governing local tumor spread. The study in its present form has been running since the year 2000 and minor modifications to the study protocol have been made. The current protocoll was approved as amendment by our institutional ethics review board in 2013.

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Brief Summary in Scientific Language

Total mesometrial resection (TMMR), extended mesometrial resection (EMMR), intracervical resection (ICR), lateral* extended pelvic resection (L*EER) and therapeutic pelveo-lumbal lymph node dissection (t-lpPND) are surgical treatment approaches for patients with cervical and vaginal carcinomas based on the theory of ontogenetic cancer fields. The aim of these techniques is to resect the malignant tumors with microscopically free margins and (except for ICR) to remove ontogenetically related tissue at high risk for occult tumor spread. Tissues close to the tumor are retained if they belong to ontogenetic domains non-permissive for the tumor at its assumed ontogenetic stage assessed pre- and intraoperatively. Therapeutic lymph node dissection is another integral part of the treatment strategy. No postoperative radiotherapy is administered if the treatment rules have been met. The ongoing investigation addresses the treatment related morbidity and sequelae. In addition, the oncological outcome in terms of recurrence free and overall survival are assessed.

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Organizational Data

  •   DRKS00015171
  •   2018/10/29
  •   [---]*
  •   yes
  •   Approved
  •   012/13-ff, Ethikkommission an der Medizinischen Fakultät der Universität Leipzig
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Secondary IDs

  • [---]*
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Health Condition or Problem studied

  •   C53 -  Malignant neoplasm of cervix uteri
  •   C52 -  Malignant neoplasm of vagina
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Interventions/Observational Groups

  •   Cancer field resection. Depending on tumor stage this accomplished as total mesometrial resection (TMMR), extended mesometrial resection (EMMR) or laterally extended endopelvic resection (LEER). In all cases, local treatment is combined with therapeutic pelveo-lumbal lymph node dissection. No adjuvant radiation is administered. In case of 2 or more lymph node metastases, the study participants is offered adjuvant chemotherapy with cisplatin 40mg/m2 over 6 cycles (every 21 days).
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Characteristics

  •   Interventional
  •   [---]*
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   N/A
  •   N/A
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Primary Outcome

Complications and sequelae of treatment, recurrence-free survival, disease-specific survival.
Regular follow-up examinations are performed every 3 months for two years and every 6 months thereafter for 3 years. Documentation of morbidity and sequelae is accomplished using the Franco-Italian glossary (Chassagne et al. Radiother Oncol 1993; 26: 195-202) during the hospital stay of primary treatment and at the aftercare visits.
In case of symptoms and/or clinical suspicion of tumor recurrence, pelvic MRI and core biopsies are performed to exclude pelvic recurrences. (PET)CT ± biopsies are done for diagnosis of distant recurrences. In case a patient misses an follow-up appointment, she is contacted via telephone in order to assess her status. If this is not possible, her gynecologist or family physician are contacted. If survival- and recurrence status cannot be retrieved, the central and local cancer registries are contacted for further information. If still no survival-information can be obtained, the patient is declared "lost for follow-up".

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Secondary Outcome

Histopathological tumor assessment with respect to ontogenetic anatomy, analysis of relapse patterns with regard to ontogenetic anatomy, overall survival. The histopathological assessment is accomplished on the surgical routine specimen. In addition to routine pathological investigations, the different ontogenetic-anatomic structures are identified in the specimen and each structure is assessed for tumor involvement. Recurrence patterns are analyzed using MRI and biopsy data. Overall survival is assessed as described above (primary endpoints).
The endpoints are evaluated continuously at the follow-up visits and yearly for all patients who did not present to these appointments.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2000/11/08
  •   600
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

Patients with histologically proven cervical carcinoma FIGO stages I B to II B or Müllerian vaginal carcinoma FIGO stage I or II without clinical evidence of involvement of the urethrovesical wall.
OR: Patients with histologically proven cervical carcinoma FIGO stages IIB / vaginal carcinoma FIGO stage II suspect for urethrovesical wall involvement or cervical carcinoma FIGO stages IIIA, B, IVA / Müllerian vaginal carcinoma FIGO stages III, IVA. In theses cases, the patients must insist on surgical treatment even after consultation with an radio-oncologist for information about the standard therapy.

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Exclusion Criteria

Compromised general condition (Karnowsky index < 80%) or other comorbidity rendering the necessary surgery an inacceptable risk. Physical or psychological inability to cope with the expected sequelae of the operation. Previous pelvic radiation.
Previous major pelvic surgery (excluding simple hysterectomy). Advanced tumors infiltrating derivatives of external somatic coelom. Neuroendocrine tumors.

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Addresses

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    • Universitätsklinikum Leipzig
    • Liebigstr. 18
    • 04103  Leipzig
    • Germany
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    • Leipzig School of Radical Pelvic Surgery
    • Mr.  Prof. Dr. Dr.  Michael  Höckel 
    • Liebigstr. 20a
    • 04103  Leipzig
    • Germany
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    • Klinik und Poliklinik für GynäkologieUniversitätsklinikum Leipzig
    • Ms.  Prof. Dr.  Bahriye  Aktas 
    • Liebigstr. 20a
    • 04103  Leipzig
    • Germany
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    • Klinik und Poliklinik für GynäkologieUniversitätsklinikum Leipzig
    • Mr.  Dr. med.  Benjamin  Wolf 
    • Liebigstr. 20a
    • 04103  Leipzig
    • Germany
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Sources of Monetary or Material Support

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    • Universitätsklinikum Leipzig
    • Liebigstr. 18
    • 04103  Leipzig
    • Germany
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    • Leipzig School of Radical Pelvic Surgery
    • Liebigstr. 20a
    • 04103  Leipzig
    • Germany
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Status

  •   Recruiting ongoing
  •   [---]*
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Trial Publications, Results and other Documents

  •   Höckel M. Gynecol Oncol 2003; 91: 369-77
  •   Höckel et al. Lancet Oncol 2005; 6: 751-56
  •   Höckel et al. Lancet Oncol 2009; 10: 683-92
  •   Höckel et al. Gynecol Oncol 2012; 125: 168-74
  •   Höckel et al. Lancet Oncol 2014; 15: 445-56
  •   Wolf et al. Gynecol Oncol 2017; 146: 292-98
  •   Höckel et al. Eur J Cancer 2017; 70: 99-110
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* This entry means the parameter is not applicable or has not been set.