Clinical trial NCT04111978: MAintenance Therapy With Aromatase Inhibitor in Epithelial Ovarian Cancer (MATAO)
Official title: MAintenance Therapy With Aromatase Inhibitor in Epithelial Ovarian Cancer: a Randomized Double-blinded Placebo-controlled Multi-centre Phase III Trial (ENGOT-ov54/Swiss-GO-2/MATAO), Including LOGOS (Low Grade Ovarian Cancer Sub-study).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ovarian Neoplasm Epithelial
Fallopian Tube Neoplasms
Peritoneal Neoplasms
High-grade Serous Ovarian Carcinoma (HGSOC)
Low-grade Serous Ovarian Carcinoma (LGSOC)
Ovarian Endometrioid Carcinoma
Keywords: maintenance therapy
aromatase inhibitor
primary ovarian cancer
estrogen-receptor
Lead sponsor: Swiss GO Trial Group
Sponsor class: NETWORK
Collaborators: name: AGO Study Group
name: Arbeitsgemeinschaft Gynaekologische Onkologie Austria
name: Reliable Cancer Therapies
name: Krebsliga Schweiz
name: Stiftung Guido Feger
name: Hoffmann-La Roche
name: Helsana AG
name: Novartis Pharmaceuticals
name: Anticancer Fund, Belgium
First posted: 2019-10-02
Enrollment: 540
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of addition of letrozole to the standard maintenance therapy in subjects following a primary diagnosis of Estrogen-receptor (ER) positive high and low grade epithelial ovarian cancer (including fallopian tube and primary peritoneal cancer) and subsequent primary treatment surgery and chemotherapy. Half of the participants will receive to the standard maintenance treatment, letrozole, whilst the other half receives placebo.

The study's primary hypothesis is that the treatment with letrozole increases progression free survival in comparison to the maintenance standard treatment (superiority trial).

Detailed description: Femara (letrozole) is an extensively investigated, marketed aromatase inhibitor (AI) widely used as treatment in the maintenance phase of estrogen-receptor (ER) positive breast cancer, as it inhibit the synthesis of estrogens. Estrogen is a well known driver of cancer growth in ER-positive tumors and a high percentage of the epithelial ovarian cancers express ER as well. Of which low grade ovarian cancers demonstrates the highest level of expression, supporting our strategy of a sub-group analysis (LOGOS). Therefore, letrozole in this study be investigated prospectively and evaluated as maintenance therapy after standard surgical and chemotherapy treatment in comparison to placebo (which is the current standard maintenance treatment) in subjects with primary, ER-positive low or high grade serous or endometrioid epithelial ovarian cancer (including fallopian tube and primary peritoneal cancer) of FIGO Stage II-IV, whose cancer has not progressed by the end of the platinum-based chemotherapy.

The objectives are to evaluate the letrozole maintenance treatment compared to placebo in terms of

* progression-free survival (PFS; primary endpoint)
* overall survival (OS)
* quality-adjusted progression free survival (QAPFS)
* time to first subsequent treatment (TFST)
* quality-adjusted time without symptoms of toxicity (Q-TWiST)
* health related quality of life (QoL) assessed by EQ-5D-5L, FACT-ES and FACT-O questionnaires

Methods: 540 for this study eligible subjects are 1:1 allocated in this randomized, controlled, double-blinded, multi-centre study to either the test (letrozole) or control (placebo) group. The maximum maintenance treatment duration is 5 years or until symptoms of toxicity or progression of underlying disease.

Health and health-related quality of life will continuously be assessed at study entry and during routine recalls which are scheduled every 12 weeks for the first 2 years, followed by every 24 weeks for the next 3 years. Procedures performed to assess the participants' health are the same as are performed during the regular routine ovarian cancer follow-up visits: blood tests, physical as well as gynaecological examinations and may include imaging. In addition, the participants are asked to complete during the study quality of life (QoL) specific questionnaires and wear an activity tracker for one week just before the scheduled visits. These assessments will be used for the evaluation of letrozole's efficacy and burden in comparison to the standard maintenance treatment. Survival follow-up data after the mainentance treatment duration of 5 years (study end) are obtained for up to another 7 years.

Eligibility criteria: Inclusion Criteria:

* Patients must be ≥ 18 years of age
* Willing and able to attend the visits and to understand all study-related procedures.
* Primary, newly diagnosed FIGO Stage II to IV and histologically confirmed low or high grade serous or endometrioid epithelial ovarian/fallopian tube/peritoneal cancer
* (Interval-) debulking performed ECOG-Performance Status 0-2
* Signed informed consents (ICF-1; ICF-2)
* Paraffin-embedded tissue or paraffin-embedded cell block (from ascites) available
* Positivity (≥ 1%) for ER expression (only determined by Histopathology Core Facility of MATAO trial)
* At least 4 cycles of platinum-based chemotherapy (neoadjuvant allowed)
* Negative serum pregnancy test in women of childbearing potential who will get/have gotten a surgical resection or radiation sterilization, prior to the intervention in the therapeutical maintenance setting.

Exclusion Criteria:

* Progressive disease at the end of adjuvant treatment as defined in chapter 9.2.1 of protocol
* Women of childbearing potential (not having undergone a surgical or radiation sterilization and not getting a surgical resection, prior to the intervention in the therapeutical maintenance setting)
* Pregnant or lactating women
* Any other malignancy within the last 5 years which has impact on the prognosis of the patient
* \< 4 cycles of chemotherapy in total
* Contraindications to endocrine therapy
* Inability or unwillingness to swallow tablets
* Patients with a known intolerance to galactose, lactase deficiency and glucose-galactose malabsorption

Primary outcomes:
measure: Progression-free survival (PFS) for each study group
timeFrame: Up to approximately 12 years
Secondary outcomes:
measure: Overall survival (OS) for each study group
timeFrame: Up to approximately 12 years
measure: Quality-adjusted progression free survival (QAPFS) for each study group
timeFrame: Up to approximately 12 years
measure: Time to first subsequent treatment (TFST) for each study group
timeFrame: Up to approximately 12 years
measure: Quality-adjusted time without symptoms of toxicity (Q-TWiST) for each study group
timeFrame: Up to approximately 12 years
measure: Health related quality of life (QoL) assessed byFunctional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) questionnaire for each study group
timeFrame: Up to approximately 5.25 years
measure: Health related quality of life (QoL) assessed by Functional Assessment of Cancer Therapy - Ovarian (FACT-O) questionnaire for each study group
timeFrame: Up to approximately 5.25 years
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Krankenhaus der Barmherzigen Brüder Graz
city: Graz
country: Austria
facility: Medizinische Universität Graz
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Leoben
country: Austria
facility: Landeskrankenhaus Hochsteiermark Leoben
city: Linz
country: Austria
facility: Ordensklinikum Linz Barmherzige Schwestern
city: Salzburg
country: Austria
facility: Universitätsklinikum Salzburg
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Wien
country: Austria
facility: Klinik Hietzing Wien
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin Campus Virchow Klinikum
city: Deggendorf
country: Germany
facility: Donauisar Klinikum
city: Düsseldorf
country: Germany
facility: Evangelisches Krankenhaus Düsseldorf
city: Essen
country: Germany
facility: Evangelische Kliniken Essen Mitte GmbH
city: Esslingen
country: Germany
facility: Klinikum Esslingen
city: Freiburg
country: Germany
facility: University Hospital Freiburg
city: Hildesheim
country: Germany
facility: Gynäkologisch-Onkologische Gemeinschaftspraxis Dres. med. C.Uleer/J.Y.Pourfard
city: Konstanz
country: Germany
facility: Klinikum Konstanz
city: Köln
country: Germany
facility: St. Elisabeth-Krankenhaus
city: Münster
country: Germany
facility: University Hospital Münster
city: Ravensburg
country: Germany
facility: Studienzentrum Onkologie Ravensburg
city: Schweinfurt
country: Germany
facility: Leopoldina Krankenhaus der Stadt Schweinfurt
city: Wiesbaden
country: Germany
facility: Helios Dr. Horst Schmidt Kliniken Wiesbaden
city: Wolfsburg
country: Germany
facility: AMO Wolfsburg / AMO MVZ GmbH
city: Basel
country: Switzerland
facility: Universitätsspital Basel
state: Basel Stadt
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau AG
state: Kanton Aargau
city: Bellinzona
country: Switzerland
facility: Oncology Institute of Southern Switzerland (IOSI)-Ente Ospedaliero Cantonale (EOC)
state: Ticino
city: Baden
country: Switzerland
facility: Kantonsspital Baden AG
city: Basel
country: Switzerland
facility: Basel Claraspital AG
city: Bern
country: Switzerland
facility: Universitätsklinik für Medizinische Onkologie, Inselspital
city: Bern
country: Switzerland
facility: Praxis im Frauenzentrum Lindenhofspital
city: Chur
country: Switzerland
facility: Kantonspital Graubünden (KSGR),
city: Frauenfeld
country: Switzerland
facility: Kantonsspital Frauenfeld
city: Geneva
country: Switzerland
facility: Hôpitaux Universitaires de Genève
city: Grabs
country: Switzerland
facility: Frauenklinik Spital Grabs
city: Lausanne
country: Switzerland
facility: Universitätsspital Waadt/ CHUV
city: Liestal
country: Switzerland
facility: Kantonsspital Baselland
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: Luzern
country: Switzerland
facility: Tumorzentrum Hirslanden Klinik St. Anna
city: Münsterlingen
country: Switzerland
facility: Kantonsspital Münsterlingen
city: Saint Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zürich
country: Switzerland
facility: Klinik für Onkologie und Hämatologie Hirslanden Zürich AG
city: Zürich
country: Switzerland
facility: Stadtspital Triemli
city: Zürich
country: Switzerland
facility: Unispital Zürich
Study officials:
affiliation: University Hospital Basel, Head Women's Hospital
name: Viola Heinzelmann-Schwarz, Prof. MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: McLaughlin PMJ, Klar M, Zwimpfer TA, Dutilh G, Vetter M, Marth C, du Bois A, Schade-Brittinger C, Reuss A, Bommer C, Kurzeder C, Heinzelmann-Schwarz V. Maintenance Therapy with Aromatase Inhibitor in epithelial Ovarian Cancer (MATAO): study protocol of a randomized double-blinded placebo-controlled multi-center phase III Trial. BMC Cancer. 2022 May 6;22(1):508. doi: 10.1186/s12885-022-09555-8.