Clinical Trials /

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

NCT04111978

Description:

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).

Related Conditions:
  • Fallopian Tube Endometrioid Adenocarcinoma
  • Fallopian Tube Serous Adenocarcinoma
  • Malignant Ovarian Serous Tumor
  • Ovarian Endometrioid Tumor
  • Primary Peritoneal Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: ENGOT-ov54/Swiss-GO-2/MATAO
  • SECONDARY ID: 2019-002264-27
  • SECONDARY ID: ENGOT-ov54
  • SECONDARY ID: Swiss-GO-2
  • NCT ID: NCT04111978

Conditions

  • Ovarian Neoplasm Epithelial
  • Fallopian Tube Neoplasms
  • Peritoneal Neoplasms

Interventions

DrugSynonymsArms
Letrozole 2.5mgFemaraLetrozole (aromatase inhibitor)

Purpose

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).

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.
    

Trial Arms

NameTypeDescriptionInterventions
Letrozole (aromatase inhibitor)ExperimentalLetrozole (Femara), 2.5 mg tablet, administered once daily for 5 years or until symptoms of toxicity or progression of underlying disease
  • Letrozole 2.5mg
PlaceboPlacebo ComparatorPlacebo tablet of Femara (without aromatase inhibitor), 2.5 mg tablet, administered once daily for 5 years or progression of underlying disease

    Eligibility 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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Progression-free survival (PFS) for each study group
    Time Frame:Up to approximately 12 years
    Safety Issue:
    Description: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

    Measure:Overall survival (OS) for each study group
    Time Frame:Up to approximately 12 years
    Safety Issue:
    Description: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.
    Measure:Quality-adjusted progression free survival (QAPFS) for each study group
    Time Frame:Up to approximately 12 years
    Safety Issue:
    Description: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.
    Measure:Time to first subsequent treatment (TFST) for each study group
    Time Frame:Up to approximately 12 years
    Safety Issue:
    Description: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.
    Measure:Quality-adjusted time without symptoms of toxicity (Q-TWiST) for each study group
    Time Frame:Up to approximately 12 years
    Safety Issue:
    Description: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.
    Measure: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
    Safety Issue:
    Description: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.
    Measure: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
    Safety Issue:
    Description: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.

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Swiss Go Trial Group

    Trial Keywords

    • maintenance therapy
    • aromatase inhibitor
    • primary ovarian cancer
    • estrogen-receptor

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