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
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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||540 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
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
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
Placebo tablet of Femara
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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
|Contact: Pamela McLaughlin, PhD||+41 61 328 42 firstname.lastname@example.org|
|Contact: Claudine Bommer||+41 61 328 42 email@example.com|
|Principal Investigator:||Viola Heinzelmann-Schwarz, Prof. MD PhD||University Hospital Basel, Head Women's Hospital|