Open label Phase I Study of Everolimus(RAD001) plus Doxorubicin in advanced progressive and refractory thyroid cancer

Phase 1

• Conditions: C73; Malignant neoplasm of thyroid gland

• Registration Number: DRKS00000635
• Lead Sponsor: niversitätsklinikum Halle (Saale)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-12-10
• Study Completion: 2017-05-09
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 14

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

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 < 9g/dl, platelets < 120.000/mm³ or absolute neutrophile count < 1.500/mm³)
9. Serum creatinine > 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

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of Doxorubicin co-administered every three weeks with RAD001 p.o. continuously

Secondary Outcome Measures

Name	Time	Method
- 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)]<br>- Progression free survival<br>- Overall survival and Response rates (according to RECIST v1.1)