C73
Conditions
Interventions
Group 1: Combination of Doxorubicin and Everolimus (RAD001) according to the following dose escalation scheme (3-6 Patienten per dose level until maximum tolerable dosis (MTD) is reached:
D1 Everolimu
D2 Everolimus 5mg daily p.o.+Doxorubicin 60 mg/m2 every 3 weeks i.v.
D3 Everolimus 10mg daily p.o.+Doxorubicin 50 mg/m2 every 3 weeks i.v.
D2 Everolimus 10mg daily p.o.+Doxorubicin 60 mg/m2 every 3 weeks i.v.
If MTD is reached at D1 the following scheme will applie:
D1 Everolimus 2.5mg daily p.o.+Doxorubicin 40 mg/m2 every 3 weeks i.v.
D2 Everolimus 5mg daily p.o.+Doxorubicin 40 mg/m2 every 3 weeks i.v.
Everolimus 10mg tgl daily+Doxorubicin 40 mg/m2 every 3 weeks i.v.
Patients responding to treatment are allowed to stay on their current dose of RAD001 until disease progression but no longer than a period of one year after their last doxorubicin treatment within thi
Sponsors
Universitätsklinikum Halle (Saale)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age = 18 2. Histologically or cytologically diagnosed thyroid cancer of follicular origin including papillary, follicular or poorly differentiated (insular or large-cell) thyroid cancer 3. Patients with progressive disease within 3 months according to RECIST-criteria or symptomatic disease (e.g. dyspnea due lung metastasis or bone pain) at the time of screening in the absence of documented disease progression with no further surgical treatment options and which are refractory or not susceptible to radioiodine treatment and if applicable, are refractory to treatment with sorafenib. 4. ECOG performance status = 2 5. Measurable lesion(s) according to RECIST-criteria v1.1 6. Adequate organ and bone marrow function 7. Agreement to use effective contraception while on treatment and for at least 3 months after end of treatment 8. Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001 9. Signed informed consent and willingness and ability to comply with study procedures
Exclusion criteria
Exclusion criteria: 1. Previously received investigational sorafenib therapy within 4 weeks before enrolment in the study 2. Previous conventional chemotherapy or any investigational anticancer therapy other than sorafenib 3. Prior therapy with mTOR inhibitors 4. Second malignancy or history of malignancy within the last 5 years 5. Clinically significant active infection requiring antibiotic or antiretroviral therapy 6. Clinically active brain metastasis, uncontrolled seizure disorder, spinal cord compression, or carcinomatous meningitis 7. Medical history of clinically significant pulmonary or cardiovascular disease including chronic heart failure or myocardial infarction within 6 month prior to study enrollment or serious uncontrolled cardiac arrhythmia 8. Significant hepatic or hematological abnormality (i.e. transaminase levels > 2.5 x ULN, serum bilirubin > 1.5 x ULN, hemoglobin 1.5 x ULN 10. Uncontrolled hyperlipidemia : Fasting serum cholesterol > 300mg/dl or > 7.75mmol/l AND fasting triglycerides > 2.5 x ULN 11. Uncontrolled diabetes mellitus as defined by fasting serum glucose > 1.5 x ULN 12. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus. 13. Patients with bleeding diathesis or an oral anti-vitamin K medication (except low dose warfarin) 14. A known history of HIV or HCV seropositivity 15. Pregnancy or breastfeeding 16. Situations that limit compliance with study requirements such as therapy schedules, lab investigations and other study procedures 17. Patients of childbearing/reproduction potential without highly effective contraception (PEARL-Index < 1%) 18. Patients with other significant disease or disorders that are considered contraindications according to the prescribing information for Doxorubicin or Affinitor or that, in the investigator’s opinion, would exclude the patient from the study 19. Patients who are incapable of giving legal informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of Doxorubicin co-administered every three weeks with RAD001 p.o. continuously | — |
Secondary
| Measure | Time frame |
|---|---|
| - Safety [safety assessments will include physical examinations, vital signs, clinical laboratory profile and monitoring of adverse events (according to NCI-CTC-AE v.4.0)] - Progression free survival - Overall survival and Response rates (according to RECIST v1.1) | — |
Countries
Germany
Contacts
Public ContactThomas Kegel
Universitätsklinikum Halle (Saale) Klinik Für Innere Medizin IV
Outcome results
None listed