A phase II study to investigate the efficacy of RAD001 (Afinitor®, everolimus) in patients with irresectable recurrent or metastatic differentiated, undifferentiated (anaplastic) and medullary thyroid carcinoma - THYRRAD, CRAD001CNL08T

• Conditions: Patients with irresectable recurrent or metastatic differentiated, undifferentiated (anaplastic) and medullary thyroid carcinoma will be treated in a phase II study to investigate the efficacy of RAD001 (Afinitor®, everolimus).

• Registration Number: EUCTR2009-016669-27-NL
• Lead Sponsor: eiden University Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01-28
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

TARGET POPULATION:
Patients with differentiated thyroid cancer comprise the main part of this study. A total number of 28 patients with differentiated thyroid cancer will be studied.

Inclusion Criteria:
•Age > 18 years
•Karnofsky performance score > 70%
•Patients with differentiated thyroid carcinoma (i.e. papillary and follicular carcinomas)
•Patients must have undergone total thyroidectomy (and having received thyrosuppressive therapy afterwards)
•Patients with no RaI uptake in tumor as proven by RaI scintigraphy performed after prior RaI therapy
•Patients with insufficient RaI uptake as proven by progression of lesions despite accumulation of RaI
•Patients with a maximum cumulative dosis of RaI
•The patient has documented progressive disease (PD) on computerized tomography (CT), magnetic resonance imaging (MRI), bone scan or X-ray, per RECIST v1.1 at screening compared with a previous image done within 14 months of screening
•Measurable tumor according to RECIST v1.1 criteria (see Section 7 on evaluation of response). Patients must have clinically and/or radiographically documented measurable disease. All radiology studies must be performed within 28 days prior to registration
•The subject has no other diagnosis of malignancy (unless non-melanoma skin cancer, carcinoma in situ of the cervix, or a malignancy diagnosed = 2 years previously) and currently has no evidence of malignancy (unless non-melanoma skin cancer or carcinoma in situ of the cervix).
•Patients with history of brain metastasis who are neurologically stable following definitive radiation and/or surgery and do not require corticosteroids will be permitted.

Laboratory Requirements - within 14 days prior to enrollment:
•Patients with adequate bone marrow function defined as ANC = 1.5 x 109/L, Platelets = 100 x 109/L, Hb = 5.6 mmol/L
•Patients with adequate liver function defined as serum bilirubin = 1.5 x ULN, ALT and AST = 2.5x ULN. Patients with known liver metastases are allowed to have an AST and ALT = 5x ULN.
•Patients with adequate renal function defined as serum creatinine = 2 x ULN.
•Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to the first dose of study drug.
•Patients must give written informed consent for inclusion in the study according to local guidelines.

Patients with progressive metastases or inoperable recurrent disease of undifferentiated (anaplastic) or medullary thyroid cancer will also have the opportunity to participate in this study, since there is a lack of therapeutic options for these patients. The same inclusion and exclusion criteria will be used, apart from the criteria on RaI therapy, since this is not applicable for undifferentiated or medullary thyroid cancer. We will analyse these patients as separate cohorts. Patients with undifferentiated or medullary thyroid cancer will be treated and evaluated according to the same criteria as the patients included with differentiated thyroid cancer. A minimum of 7 undifferentiated thyroid cancer patients and 7 medullary thyroid cancer patients will be analysed for response rate; if no responses are found in these patient groups, further investigation of RAD001 in undifferentiated or medullary thyroid cancer patients is not warranted.

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

Exclusion Criteria

Exclusion Criteria:
•Patients receiving chemotherapy, immunotherapy, radiation therapy or any other investigational agent within 4 weeks of the first dose of study drug, or sunitinib and/or sorafenib within 2 weeks of the first dose of RAD001. Patients must have recovered from effects of prior therapy.
•Patients who have previously received RAD001 or other mTOR inhibitors.
•Patients with known hypersensitivity to RAD001 or other rapamycin analogs (sirolimus, temsirolimus), or to its excipients.
•Patients receiving chronic, systemic treatment with corticosteroids or another
immunosuppressive agent (except corticosteroids with a daily dosage equivalent to
prednisone = 20 mg for adrenal insufficiency). Patients receiving corticosteroids must be on a stable dose for = 4 weeks prior to the first dose of RAD001. Topical or inhaled corticosteroids are permitted.
•Patients with an active bleeding diathesis.
•Patients who have undergone major surgery within 4 weeks prior to starting study drug (e.g., intra-thoracic, intra-abdominal, or intra-pelvic), open biopsy, or significant traumatic injury, or who have not recovered from the side effects of any of the above.
•Patients with any severe and/or uncontrolled medical conditions such as unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction = 6 months, serious uncontrolled cardiac arrhythmia, uncontrolled hyperlipidemia, active or uncontrolled severe infection, cirrhosis, chronic or persistent active hepatitis or severely impaired lung function. Investigation of LVEF can be performed in case of doubt for in/exclusion.
•Uncontrolled diabetes (fasting glucose > 2 x ULN).
•Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not willing to use effective birth control methods. If barrier contraceptives are used, they must be continued throughout the study by both sexes.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified