Recurrent endometrial cancer MedDRA version: 9.1 Level: HLT Classification code 10014742 Term: Endometrial neoplasms malignant
Conditions
Interventions
Trade Name: CERTICAN
Pharmaceutical Form: Tablet
INN or Proposed INN: Everolimus
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: .25-
Trade Name: FEMARA
Pharmaceut
Sponsors
Oncology Institute of Southern Switzerland
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed progressive or recurrent EC (serous papillary, clear cell, endometrioid or mixed with endometrioid component histology; any grade). Patients must have documented E and/or P receptor positivity. If not assessed, the original tissue specimens should be retrieved and analyzed. If the initial tumor tissues are not available, only the patients with a history of E- dependent tumor can be included. 2. At least one prior HT for advanced disease (a maximum of 1 is allowed) in group A and at least 1 prior CT for advanced disease (a maximum of 1 is allowed) and ≤ 2 previous HT in group B. 3. Measurable disease according to RECIST criteria with documented progressive disease in the 3 months preceeding the start of the treatment. 4. Pretreatment absolute granulocyte count (i.e. segmented neutrophils + bands) of ≥ 1,500/Fl, a hemoglobin level of ≥9.0 gm/dL and a platelet count of ≥100,000/Fl. 5. Adequate renal function as documented by serum creatinine ≤2.0 mg/dL. 6. Adequate hepatic function as documented by a serum bilirubin ≤1.5 mg/dL, regardless of whether patients have liver involvement secondary to tumor. Aspartate transaminase (SGOT) must be ≤2.5 x institutional upper normal values (UNV) unless the liver is involved with tumor, in that case the aspartate transaminase must be ≤5x institutional upper limit of normal. 7. Patients must have a ECOG performance status ≤ 1. 8. Life expectancy of at least 3 months 9. Age 18-75 years old 10. Patients must have signed an approved informed consent. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Prior treatment with RAD001 or another mTOR inhibitor. 2. Mixed malignant mullerian tumors (MMMT) components and uterine sarcomas. 3. Known metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, had a negative imaging study within 4 weeks of study entry, is clinically stable with respect to the tumor at the time of study entry, and is not receiving steroid therapy or taper. 4. Prior anticancer treatment (chemotherapy, radiotherapy, hormonal, immunotherapy, biological response modifiers, signal transduction inhibitors, etc) within 4 weeks prior to the first dose of RAD001; the interval is decreased to &#8805; 2 weeks for signal transduction inhibitors with a half-life known to be <24 hours, and is &#8805; 6 weeks for nitrosourea or mitomycin. The following exceptions are allowed: nasal, ophthalmic, and topical glucocorticoid preparations a stable dose of corticosteroids for at least two weeks low dose maintenance steroid therapy for other conditions physiologic hormone replacement therapy (e.g., thyroid supplementation for thyroid deficiency or oral replacement glucocorticoid therapy for adrenal insufficiency) 5. Pre-existing malabsorption syndrome, irritable bowel syndrome or other clinical situation which could affect oral absorption 6. Ongoing toxicity associated with prior anticancer therapy (except peripheral neuropathy of &#8804; grade 1 by NCI toxicity criteria and alopecia) 7. Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin) and to everolimus or sirolimus (rapamycin), to letrozole or lactose (contained in formulations of RAD001 and letrozole). 8. Active infection requiring systemic therapy. 9. Known HIV infection 10. History of psychiatric disorders that would interfere with consent or follow-up. 11. History of myocardial infarction within the previous six months or congestive heart failure requiring therapy. 12. Previous malignancy (except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer) or other cancer for which the patient has been disease-free for at least five years. 13. History of seizures. Patients receiving phenytoin, phenobarbital, or other antiepileptic prophylaxis are ineligible. 14. Any other severe concurrent disease which would make the patient inappropriate for entry into this study, including significant hepatic, renal, or gastrointestinal diseases.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To define the antitumor activity (according to RECIST) of the combination of RAD001 and Letrozole in patients with recurrent endometrial cancer;Secondary Objective: To define the safety profile of the combination after repeated administrations in patients with recurrent endometrial cancer;Primary end point(s): Objective clinical response | — |
Countries
Italy
Outcome results
None listed