Biomarker Guided Treatment in Gynaecological Cancer

NCT ID: NCT02543710

Last Updated: 2017-03-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 1300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2033-12-31

Brief Summary

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.

Conditions

Endometrial Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Biomarker (ER/PR) guided lymphadenectomy

Intervention Type: PROCEDURE

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.

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.

Group Type: EXPERIMENTAL

Biomarker guided weekly taxane treatment in endometrial/ ovarian cancer

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: PROCEDURE

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

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

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

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 95 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Haukeland University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Henrica MJ Werner, MD PhD MRCOG

Role: PRINCIPAL_INVESTIGATOR

Haukeland University Hospital

Locations

Radboud university hospital

Nijmegen, , Netherlands

Site Status: NOT_YET_RECRUITING

Women's hospital, Haukeland university hospital

Bergen, Hordaland, Norway

Site Status: RECRUITING

Ålesund hospital

Ålesund, , Norway

Site Status: RECRUITING

Førde central hospital

Førde, , Norway

Site Status: RECRUITING

Sørlandet hospital

Kristiansand, , Norway

Site Status: NOT_YET_RECRUITING

Akershus University hospital

Oslo, , Norway

Site Status: RECRUITING

Stavanger university hospital

Stavanger, , Norway

Site Status: RECRUITING

St Olav university hospital

Trondheim, , Norway

Site Status: RECRUITING

Spsk No 1

Lublin, , Poland

Site Status: RECRUITING

Countries

Netherlands; Norway; Poland

Central Contacts

Jone Trovik, MD PhD Prof

Role: CONTACT

jone.trovik@k2.uib.no

+4755974200

Henrica MJ Werner, MD PhD MRCOG

Role: CONTACT

henrica.werner@k2.uib.no

+4755974200

Facility Contacts

Hanny MA Pijnenborg, MD, PhD

Role: primary

Casper Reijne, MD

Role: backup

Henrica MJ Werner, MD, PhD

Role: primary

heaw@helse-bergen.no

+4755974200

Jone Trovik, prof MD PhD

Role: backup

jone.trovik@uib.no

+4755974200

Margaret S Lode, MD

Role: primary

Jostein Tjugum, MD

Role: primary

marthe LT Larsson, MD

Role: backup

Ane C Munk, MD, PhD

Role: primary

ingvild Vistad, MD, PhD

Role: backup

marie E Engh, MD

Role: primary

Elisabeth B Nilsen, MD

Role: primary

Nina Nordskar, MD

Role: primary

Solveig Tingulstad, MD

Role: backup

Bartolomiej Barczynski, MD, PhD

Role: primary

References

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.

Reference Type: DERIVED

PMID: 34400137 (View on PubMed)

Other Identifiers

2015/548

Identifier Type: -

Identifier Source: org_study_id