Primary low-grade serous carcinoma of the ovary or peritoneum. MedDRA version: 20.0 Level: LLT Classification code 10007107 Term: Cancer of ovary System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10026340 Term: Malignant neoplasm of peritoneum, unspecified System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Femara®
Product Name: Letrozole
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Letrozole
CAS Number: 112809-51-5
Concentration unit: mg milligram(s)
Concentration type: equa
Sponsors
Cancer Trials Ireland
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient cannot be considered eligible for this study unless ALL of the following conditions are met. 1. Patients must have newly diagnosed, Stage II-IV low-grade serous ovarian cancer (submission of pathology report(s) required). Ovarian cancer = ovarian, fallopian tube and primary peritoneal cancers. NOTE: Patients with a prior history of serous borderline tumors but a new diagnosis of Stage II-IV low-grade serous ovarian cancer are eligible. • p53 immunohistochemistry (IHC) is required and must show nonaberrant pattern (nonaberrant p53 expression is consistent with normal/wildtype TP53). If aberrant p53 expression is found on p53 IHC, the patient is NOT eligible (e.g., aberrant p53 expression is consistent with mutant TP53 and supports a diagnosis of high grade serous ovarian cancer). 2. Appropriate stage for study entry based on the following diagnostic workup: o History/physical examination within 14 days prior to registration; o Contrast-enhanced imaging of the chest, abdomen and pelvis within 28 days prior to registration. 3. Age = 18 4. Patients must have undergone an attempt at maximal upfront cytoreductive surgery, with either optimal (1 cm diameter residual disease/nodule) status allowed. 5. Patients must have undergone a bilateral salpingo-oophorectomy 6. Patients must have an ECOG Performance Status of 0, 1 or 2 within 14 days prior to registration (protocol Appendix I). 7. Patients must be within =8 weeks of primary cytoreductive surgery at time of randomization. 8. Patients must be able to take per oral (P.O.) medications. 9. Patients must have adequate organ and marrow function as defined below: 9.1. Bone marrow function within 14 days prior to registration defined as follows: o Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl o Platelets greater than or equal to 100,000 cells/mcl 9.2. Adequate renal function within 14 days prior to registration defined as follows: o Creatinine less than or equal to 1.5 x ULN 9.3. Adequate hepatic function within 14 days prior to registration defined as follows: o Bilirubin less than or equal to 1.5 x ULN o ALT and AST less than or equal to 3 x ULN 10. The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information. 11. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 225 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 225
Exclusion criteria
Exclusion criteria: Patients with any of the following conditions are NOT eligible for this study. 1. Patients may not have received neoadjuvant or adjuvant chemotherapy or radiotherapy for the treatment of this disease. 2. Patients may not have received previous hormonal therapy for the treatment of this disease. 3. Patients with known hypersensitivity to letrozole or hypersensitivity/intolerance to carboplatin/paclitaxel therapy. 4. Patients with severe cardiac disease: • Myocardial infarction or unstable angina within 6 months prior to registration. • New York Heart Association (NYHA) Class II or greater congestive heart failure (protocol Appendix II). 5. Patients with known central nervous system metastases 6. Patients with active (except for uncomplicated urinary tract infection) or uncontrolled systemic infection. 7. Patients with =grade 2 baseline neuropathy 8. Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To examine if letrozole monotherapy/maintenance (L/L) is non-inferior to IV paclitaxel/carboplatin and maintenance letrozole (CT/L) with respect to PFS in women with stage II-IV primary low-grade serous carcinoma of the ovary or peritoneum after primary surgical cytoreduction.;Secondary Objective: 1. To compare the nature, frequency and maximum degree of toxicity as assessed by CTCAE v5.0 for each treatment arm. 2. To compare the relative frequency of objective tumour response in those with measurable disease after cytoreductive surgery for each treatment arm. 3. To compare overall survival for each treatment arm. 4. To compare the CT\L and L\L arms with respect to patients adherence to letrozole therapy as measured by pill counts.;Primary end point(s): The primary efficacy endpoint is Progression Free Survival (PFS). PFS is defined as the time (in months) from the randomized treatment assignment to documentation of disease progression (RECIST 1.1) or death from any cause, whichever comes first.;Timepoint(s) of evaluation of this end point: The study includes two interim analyses. At 20% information time, a futility analysis will be conducted. At 40% information time, both efficacy and futility will be assessed. The PFS comparison will be assessed at the second interim and final analyses using a logrank test stratified by country and residual disease status. Full analysis will be performed after the date on which the last participant was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Toxicity • Objective Tumour Response • Overall Survival • Adherence to Letrozole Maintenance Therapy ;Timepoint(s) of evaluation of this end point: The study includes two interim analyses. At 20% information time, a futility analysis will be conducted. At 40% information time, both efficacy and futility will be assessed. Full analysis will be performed after the date on which the last participant was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events. | — |
Countries
Canada, Ireland, Korea, Republic of, United States
Contacts
Public ContactHead of Clinical Operations
Cancer Trials Ireland
Outcome results
None listed