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MAintenance Therapy With Aromatase Inhibitor in Epithelial Ovarian Cancer (MATAO) (MATAO)

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ClinicalTrials.gov Identifier: NCT04111978
Recruitment Status : Not yet recruiting
First Posted : October 2, 2019
Last Update Posted : October 2, 2019
Sponsor:
Collaborators:
AGO Study Group
Arbeitsgemeinschaft Gynaekologische Onkologie Austria
Information provided by (Responsible Party):
Swiss Go Trial Group

Brief Summary:

The purpose of this study is to evaluate the efficacy of the addition of letrozole to the standard maintenance therapy in subjects following a primary diagnosis of Estrogen-receptor (ER) positive epithelial ovarian cancer (including fallopian tube and primary peritoneal cancer). Half of the participants will receive in addition to the standard maintenance treatment letrozole, while the other half receives the current standard treatment.

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


Condition or disease Intervention/treatment Phase
Ovarian Neoplasm Epithelial Fallopian Tube Neoplasms Peritoneal Neoplasms Drug: Letrozole 2.5mg Other: Placebo Phase 3

Detailed Description:

Femara (letrozole) is a extensively investigated, marketed aromatase inhibitor (AI) widely used as treatment in estrogen-receptor (ER) positive breast cancer. IAs inhibit the synthesis of estrogen. Estrogen is a driver of cancer growth in ER positive tumors. A high percentage of epithelial ovarian cancer express also the ER. Letrozole seems therefore a potent drug for subjects with ovarian cancer too and shall 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 (only domain: additional concerns) and EORTC-QLQ OV-28 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 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 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 540 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Estimated Study Start Date : January 1, 2020
Estimated Primary Completion Date : July 1, 2025
Estimated Study Completion Date : July 1, 2030

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer
Drug Information available for: Letrozole

Arm Intervention/treatment
Experimental: Letrozole (aromatase inhibitor)
Letrozole (Femara), 2.5 mg tablet, administered once daily for 5 years or until symptoms of toxicity or progression of underlying disease
Drug: Letrozole 2.5mg
Aromatase inhibitor
Other Name: Femara

Placebo Comparator: Placebo
Placebo tablet of Femara (without aromatase inhibitor), 2.5 mg tablet, administered once daily for 5 years or progression of underlying disease
Other: Placebo
Placebo tablet of Femara




Primary Outcome Measures :
  1. Progression-free survival (PFS) for each study group [ Time Frame: Up to approximately 12 years ]

    PFS defined as the time from the date of first IMP administration until the date of progression (recurrence) or death by any cause in the absence of progression.

    Assessment of progression (recurrence) is generally indicated by SYMPTOMS and will be assessed by the investigator most commonly on the basis of CT scans of the pelvis, abdomen and thorax, according to RECIST v1.1 criteria recommended and mostly presented by an elevated CA-125 level. Elevated CA-125 levels alone shouldn't be considered as progression. Progression assessment according to local standard of care, however, is similarly acceptable.



Secondary Outcome Measures :
  1. Overall survival (OS) for each study group [ Time Frame: Up to approximately 12 years ]
    OS defined for each patient as the time from the date of first IMP administration until the date of death from any cause. Patients not having an event at the time of analysis will be censored at the date they were last known to be alive.

  2. Quality-adjusted progression free survival (QAPFS) for each study group [ Time Frame: Up to approximately 12 years ]

    QAPFS defined as the time from the date of first IMP administration until the date of progression (recurrence) or death by any cause in the absence of progression under consideration of the quality of life during this period. QAPFS incorporates progression-free survival (quantity) and quality of life during this period into a measure of net clinical benefit:

    QAPFS = PFS (years or months) x QoL (utility value).

    Utility values derived from the EQ-5D-L5 questionnaire will be used.


  3. Time to first subsequent treatment (TFST) for each study group [ Time Frame: Up to approximately 12 years ]
    TFST defined for each patient as the time from the date of first IMP administration until the date the patient started the next (second-line) subsequent anticancer treatment. Patients not receiving a subsequent anticancer treatment at the time of analysis will be censored at the date they were last known to be alive.

  4. Quality-adjusted time without symptoms of toxicity (Q-TWiST) for each study group [ Time Frame: Up to approximately 12 years ]

    Q-TWiST defined as the Quality adjusted Time Without appearance of any Symptoms of Toxicity related to either the progression of the cancer or side effects of the trial medication from the date of first IMP administration until dead.

    The Q-TWiST analysis considers the following three health states:

    • (1) the period experiencing toxicity (TOX)
    • (2) the period before progression without experiencing toxicity (TWiST)
    • (3) the period after relapse (REL)

    These periods are assigned preference utilities (u), which will be derived using the generic EQ-5D-5L questionnaire.

    The Q-TWiST will be calculated as the weighted sum of the time spent in each health state:

    Q-TWiST = uTox*TOX + TWiST + uRel*REL where u denotes the assigned utility for each respective health state.


  5. Health related quality of life (QoL) assessed by FACT-ES questionnaire (only domain: additional concerns) for each study group [ Time Frame: Up to approximately 5.25 years ]

    FACT-ES (only the domain: additional concerns) is included into the study to more specifically assess the side effects from the IMPs on quality of life.

    Secondary endpoint is the proportion of patients with a minimum important clinical difference (MICD) - to differentiate between improvement and deterioration - from baseline in the FACT-ES score at any time point during the study.


  6. Health related quality of life (QoL) assessed by EORTC-QLQ OV-28 questionnaire for each study group [ Time Frame: Up to approximately 5.25 years ]

    In the context of this study the specific ovarian cancer symptom-oriented questionnaire EORTC QLQ-OV-28 will be used to measure diminishing quality of life due to increasing symptoms of progression (recurrence).

    Secondary endpoint is the proportion of patients with a minimum important clinical difference (MICD) of ≥ 10 points (to differentiate between improvement and deterioration) from baseline in the QLQ-OV28 score at any time point during the study. A more stringent and clinically relevant 20-point MCID cutoff may be used.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years
  • 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 cell block (from ascites) available
  • Positivity (≥ 1%) for ER expression (only determined by MATAO Core Pathology Facility)
  • At least 4 cycles of platinum-based chemotherapy (neoadjuvant allowed)
  • Inclusion of a patient already in the chemotherapy phase is allowed if the G8 questionnaire, ESGO surgery questionnaire, and CCI have been routinely obtained prior to this phase
  • Negative serum pregnancy test in women of childbearing potential (women of childbearing potential defined as: premenopausal or less than 12 months of postmenopausal amenorrhea, and who have not undergone surgical or radiation sterilization)

Exclusion Criteria:

  • Progressive disease at the end of adjuvant treatment
  • Any other malignancy within the last 5 years which has impact on the prognosis of the patient
  • < 4 cycles of chemotherapy totally
  • Contraindications to endocrine therapy
  • Inability or unwillingness to swallow tablets
  • Patients with a known intolerance to galactose, lactase deficiency and glucose-galactose mal-absorption
  • Implanted ICD or/and PM
  • Impairment or disability to place the wearable on the forearm

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04111978


Contacts
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Contact: Pamela McLaughlin, PhD +41 61 328 42 04 pamela.mclaughlin@usb.ch
Contact: Claudine Bommer +41 61 328 42 04 claudine.bommer@usb.ch

Sponsors and Collaborators
Swiss Go Trial Group
AGO Study Group
Arbeitsgemeinschaft Gynaekologische Onkologie Austria
Investigators
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Principal Investigator: Viola Heinzelmann-Schwarz, Prof. MD PhD University Hospital Basel, Head Women's Hospital

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Responsible Party: Swiss Go Trial Group
ClinicalTrials.gov Identifier: NCT04111978     History of Changes
Other Study ID Numbers: ENGOT-ov54/Swiss-GO-2/MATAO
2019-002264-27 ( EudraCT Number )
ENGOT-ov54 ( Other Identifier: European Network for Gynaecological Oncological Trial Groups )
Swiss-GO-2 ( Other Identifier: Swiss Network for Gynaecological Oncological Studies )
First Posted: October 2, 2019    Key Record Dates
Last Update Posted: October 2, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Swiss Go Trial Group:
maintenance therapy
aromatase inhibitor
primary ovarian cancer
estrogen-receptor
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases
Letrozole
Aromatase Inhibitors
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists