Biomarker Guided Treatment in Gynaecological Cancer (Momatec2)

MoMaTEC2 aims to test, in clinically oriented studies, the applicability of already identified and promising molecular biomarkers, to promote individualisation of treatment for patients with endometrial cancer. Predominantly, but not exclusively, such biomarkers have shown to be interesting in retrospective analysis of our large prospectively collected MoMaTEC1 series.

Part 1: Performance of a phase 4 implementation trial for optimised stratification of surgical treatment, specifically the performance of (para-aortic and pelvic) lymphadenectomy guided by validated biomarkers.

Part 2: Performance of a phase 2b clinical biomarker study to evaluate the predictive potential of the biomarker stathmin for taxane treatment response in endometrial and ovarian cancer. In this study stathmin will be used as integrated biomarker.

Study Overview

• Status: Recruiting
• Conditions: Endometrial Cancer
• Intervention / Treatment: Procedure: Biomarker (ER/PR) guided lymphadenectomy; Drug: Biomarker guided weekly taxane treatment in endometrial/ ovarian cancer

• Study Type: Interventional
• Enrollment (Anticipated): 1300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jone Trovik, MD PhD Prof; Phone Number: +4755974200; Email: jone.trovik@k2.uib.no
• Study Contact Backup: Name: Henrica MJ Werner, MD PhD MRCOG; Phone Number: +4755974200; Email: henrica.werner@k2.uib.no

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Not yet recruiting
    • Radboud University Hospital
    • Contact: Hanny MA Pijnenborg, MD, PhD
    • Contact: Casper Reijne, MD
• Norway
  • Alesund, Norway, 6017
    • Recruiting
    • Ålesund Hospital
    • Contact: Margaret S Lode, MD
  • Førde, Norway, 6812
    • Recruiting
    • Førde Central Hospital
    • Contact: Jostein Tjugum, MD
    • Contact: marthe LT Larsson, MD
  • Kristiansand, Norway, 4604
    • Not yet recruiting
    • Sørlandet Hospital
    • Contact: Ane C Munk, MD, PhD
    • Contact: ingvild Vistad, MD, PhD
  • Oslo, Norway
    • Recruiting
    • Akershus University Hospital
    • Contact: marie E Engh, MD
  • Stavanger, Norway, 4011
    • Recruiting
    • Stavanger University Hospital
    • Contact: Elisabeth B Nilsen, MD
  • Trondheim, Norway, 7006
    • Recruiting
    • St Olav University Hospital
    • Contact: Nina Nordskar, MD
    • Contact: Solveig Tingulstad, MD
  • Hordaland
    • Bergen, Hordaland, Norway, 5053
      • Recruiting
      • Women's hospital, Haukeland university hospital
      • Contact: Henrica MJ Werner, MD, PhD; Phone Number: +4755974200; Email: heaw@helse-bergen.no
      • Contact: Jone Trovik, prof MD PhD; Phone Number: +4755974200; Email: jone.trovik@uib.no
• Poland
  • Lublin, Poland, 20-081
    • Recruiting
    • Spsk No 1
    • Contact: Bartolomiej Barczynski, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria part 1:

All patients referred to a participating research centre with suspicion of or confirmed endometrial cancer.

Exclusion Criteria part 1:

1. Patients who do not have endometrial cancer
2. Patients who will or cannot give informed consent (including language barriers)
3. Patients <18 years of age
4. Patients who will not get surgical treatment for their endometrial cancer

Inclusion criteria part 2:

1. Patients with endometrial or epithelial ovarian cancer who following routine clinical guidelines are offered weekly taxane (paclitaxel) treatment. This will often be a third or fourth line treatment, i.e. patients with advanced disease.
2. Technical possibility to obtain a new tissue biopsy to determine stathmin level in the tumour recurrence.

Exclusion criteria part 2:

1. Patients not suffering from endometrial or epithelial ovarian cancer
2. Patients <18 years of age
3. Patients who do not agree to the proposed treatment or will receive (part of) the treatment in a non-participating centre
4. Patients who cannot or do not want to give informed consent (including language barriers)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: phase 4 implementation study; The historical MoMaTEC1 outcome data, collected from 2001-2015 serve as control arm. These data have been rigorously collected and quality controlled with extensive clinical annotation and follow-up data, and reflect the outcome in (for a larger part) the same population as expected for MoMaTEC2 as there have not been major changes in surgical or medical treatment for endometrial cancer in this time period that could cause confounding. Internal validity, and to a degree also external validity, covering practice in multiple countries, should in this way be assured.	Procedure: Biomarker (ER/PR) guided lymphadenectomy; Lymphadenectomy in the pelvis and para-aortic, will, for patients who are considered otherwise low risk (endometrioid tumours grade 1 or 2, or grade 3 with <50% myometrial infiltration (MI), with no sign of extrauterine disease), be dependent on the preoperative hormone receptor status (ER and PR). Patients will be defined low risk when endometrioid, grade 1 or 2, or grade 3 with <50% MI, AND positive hormone receptor status for both ER AND PR. These patients will not undergo lymphadenectomy. Patients with endometrioid tumours grade 1 or 2, or grade 3 <50% MI,, with either negative ER or PR status, are defined high risk and will undergo pelvic and para-aortic lymphadenectomy as part of their surgical procedure. Patients will receive routine clinical follow-up for 5 years. Follow-up data will be collected for the study, focusing on survival and recurrence of disease. All patients will, as part of the study fill out validated quality of life questionnaires (QoL) at follow-up.
Experimental: phase 2b biomarker study; For the current study, stathmin is used as an integrated marker and does not dictate treatment modality, therefore there is no requirement for a control arm.	Drug: Biomarker guided weekly taxane treatment in endometrial/ ovarian cancer; A 5mm tissue biopsy will be analysed for stathmin level in the recurrence as well as urine and a second 5mm biopsy on termination of study participation. The second biopsy could help explain why patients have stopped responding to the treatment. Determination of stathmin level both from the tissue and the urine will take place at the pathology department. Stathmin serves as an integrated biomarker, which enables a central biomarker analysis at Haukeland university hospital. Stathmin level is defined as high with an immunohistochemical score 9 (max score). All other scores are considered low. Pre-treatment all patients undergo CT or MRI, maximum 1 month prior to treatment start. During treatment, urine and bloods will be collected every treatment cycle (weekly basis). Imaging will take place every 8 treatment cycles. Treatment will continue until disease progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of recurrences after primary treatment	The percentage of lymphadenectomy can be reduced safely and significantly, from 70% (MoMaTEC1 study results) to 30% in the MoMaTEC2 study through a better risk stratification of patients, especially better identification of low risk patients. Additionally The percentage of patients who need to be subjected to adjuvant (chemo) therapy can be reduced similarly from 20 to 10%, based on the same, optimised risk stratification and better identification of low risk patients. Patients will be rigorously followed during 5 years to detect any unexpected increase in the percentage of patients suffering a recurrence compared to the historical MoMaTEC1 cohort.	5 year after diagnosis
stathmin levels	stathmin level will be measured in metastatic tissue and related to response to treatment using Response Evaluation Criteria In Solid Tumors (RECIST) criteria	duration of complete or partial treatment response in metastatic setting (expected duration less than one year)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life measurements	Quality of life will be measured through validated questionnaires (EORTC QLQ-C30 and EORTC QLQ-EN24).	5 years post treatment
correlation of stathmin llevels in tumor, urine and blood	stathmin tumor levels, urine levels and blood levels will be correlated.	duration of complete or partial treatment response in metastatic setting (expected duration less than one year)

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Investigators: Principal Investigator: Henrica MJ Werner, MD PhD MRCOG, Haukeland University Hospital

Publications and helpful links

General Publications

• Forsse D, Barbero ML, Werner HMJ, Woie K, Nordskar N, Berge Nilsen E, Ellstrom Engh M, Vistad I, Rege A, Saevik-Lode M, Andreasen S, Haldorsen IS, Trovik J, Krakstad C. Longitudinal effects of adjuvant chemotherapy and lymph node staging on patient-reported outcomes in endometrial cancer survivors: a prospective cohort study. Am J Obstet Gynecol. 2022 Jan;226(1):90.e1-90.e20. doi: 10.1016/j.ajog.2021.08.011. Epub 2021 Aug 13.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2033

Study Registration Dates

• First Submitted: July 7, 2015
• First Submitted That Met QC Criteria: September 4, 2015
• First Posted (Estimate): September 7, 2015

Study Record Updates

• Last Update Posted (Actual): March 28, 2017
• Last Update Submitted That Met QC Criteria: March 24, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms; Antineoplastic Agents; Taxane
• Other Study ID Numbers: 2015/548

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO