A multicentre phase II trial to determine the efficacy of RAD 001 (everolimus, Afinitor®) as second line therapy in patients with transitional cell carcinoma (TCC) of the urothelium which failed or progressed after first line chemotherapy. - AFINIVEST
- Conditions
- Patients who have metastatic or locally advanced inoperable transitional cell carcinoma of the urothelium who failed prior systemic chemotherapy
- Registration Number
- EUCTR2010-020067-20-FR
- Lead Sponsor
- Hôpital FOCH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
1. Patient Information and written informed consent form signed
2. Patient aged 18 years old or more
3. Histologically proven advanced transitional cell carcinoma of the urothelium,
4. Metatatic or inoperable locally advanced disease
5. Disease recurring or progressing after two lines of chemotherapeutic ageents, tah have urothelial cancer as a specific indication in their RCP (as for instance Javlor)
6. Previous chemotherapy or radiotherapy must have been stopped 30 days before first dose of study treatment and patients must have recovered from any serious side effects of treatment,
7. Except if contra-indicated, patients must have been treated with two lines of chemotherapy
8. Patients must have one measurable lesion defined by RECIST criteria not previously irradiated, assessed by conventional CT-scan or MRI performed < 30 days before first day of study drug administration,
9. Patients must have a performance Status < 2 on the Eastern Cooperative Oncology Group Scale ,
10.Adequate haematological function (ANC > 1.5 x 109/L; Platelets ³ 100 x 109/L and Hb ³ 8 g/dL),
11. Adequate hepatic function: total bilirubin £ 1.5 times the upper limit of normal (ULN), ASAT and ALAT £ 2.5 x ULN or £ 5 x UNL in presence of liver metastase,
12. Adequate renal function: calculated creatinine clearance =40 ml/min according to Cockcroft and Gault formula,
13. Adequate lipid profile: total cholesterol < 300 mg/dL and triglycerides < 200 mg/dL.
14. Women and men with reproductive potential must use medically acceptable contraceptive method,
15. Patients must be affiliated to the French National Health Insurance System
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) no
F.1.3.1 Number of subjects for this age range
1. Prior treatment with radiotherapy involving more than 25 % of marrow producing area
2. Concurrent anti-cancer treatment
3. Prior treatment on RAD001
4. Symptomatic brain metastases
5. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as :
- unstable angina pectoris, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction = 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia, cerebrovascular accidents = 6 months before study treatment start
- severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
- poorly controlled diabetes as defined by fasting serum glucose >2.0 x ULN
- any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study
- nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by this study treatment.
- liver disease such as cirrhosis, decompensated liver disease, chronic active hepatitis or chronic persistent hepatitis.
6. Patients receiving chronic systemic treatment with corticosteroids (dose of = 10 mg/day methylprednisone equivalent) or another immunosuppressive agent. Inhaled and topical steroids are acceptable .
7. Patients with a known history of HIV seropositivity.
8. Treatment with anticoagulant agent with warfarin or unfractionated heparin; patients requiring anticoagulation may be entered after successful conversion to low molecular weight heparin.
9. Diagnosis of any second malignancy within the last 5 years, except basal cell carcinoma, squamous cell skin cancer, incidental PT2 prostate cancer found on a radical cystoprostatectomy material; or carcinoma in situ of the cervix that has been adequately treated with no evidence of recurrent disease for 12 months.
10. Pregnant women, women who are likely to be pregnant or are breastfeeding,
11. Hypersensitivity to the study drug, other derivatives of rapamycinen notably sirolimus and temsirolius, and/or to any the encipients notably lactose and galactose.
12. Patients with galactos intolerance, Lapp lactase deficiency or a glucose galactose malapsortion syndrome
13. Individuals deprived of liberty or placed under the authority of a tutor.
14. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and the follow-up schedule.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Progression-free survival (PFS) at 12 weeks of patients who receive RAD001 after failure of conventional chemotherapy.;Secondary Objective: 1. Progression Free Survival<br>2. Objective Response Rate (RECIST) <br>3. Safety (CTAE vs3.0)<br>4. Overall survival<br>;Primary end point(s): Progression-free survival (PFS). Progression-free survival (PFS) is the time from the date of registration to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.
- Secondary Outcome Measures
Name Time Method