E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent endometrial cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10014742 |
E.1.2 | Term | Endometrial neoplasms malignant |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To define the antitumor activity (according to RECIST) of the combination of RAD001 and Letrozole in patients with recurrent endometrial cancer |
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E.2.2 | Secondary objectives of the trial |
To define the safety profile of the combination after repeated administrations in patients with recurrent endometrial cancer |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective clinical response |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |