Contact information
Type
Scientific
Primary contact
Dr B A Zonnenberg
ORCID ID
Contact details
University Medical Centre Utrecht (UMCU)
Department of Medical Oncology
Heidelberglaan 100
Utrecht
3584 CX
Netherlands
+31 (0)30 250 6308
B.Zonnenberg@umcutrecht.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
CSTI571BNL07; METC 03-044
Study information
Scientific title
Acronym
Study hypothesis
In the pathogenesis of medullary thyroid carcinoma a mutation of the rearranged during transfection (RET) tyrosine kinase system plays an essential role. In animal models the tyrosine kinase inhibitor imatinib showed tumor regression. So a phase II study in patients with progressive medullary thyroid carcinoma with imatinib may open new treatment possibilities.
Ethics approval
Ethics approval received from the local medical ethics committee
Study design
Observational phase II study
Primary study design
Observational
Secondary study design
Single-centre
Trial setting
Other
Trial type
Treatment
Patient information sheet
Condition
Medullary thyroid carcinoma
Intervention
Oral treatment with 600 - 800 mg imatinib daily.
Intervention type
Drug
Phase
Phase II
Drug names
Imatinib mesylate (Glivec®)
Primary outcome measures
The primary objective is to determine the objective response rate (partial and complete responses) in subjects with advanced medullary thyroid carcinoma.
Secondary outcome measures
1. To determine the time to tumour progression
2. To evaluate overall survival
3. To evaluate the safety profile of Glivec® in advanced medullary thyroid carcinoma
Overall trial start date
11/07/2003
Overall trial end date
11/07/2006
Reason abandoned
Eligibility
Participant inclusion criteria
1. Patients over 18 years of age
2. The subject has advanced histologically proven medullary thyroid cancer. Advanced disease is defined as locally recurrent disease or metastatic disease that is not amenable to curative resection. The subject must have measurable disease.
3. The subject has not received anti-tumor radiotherapy or chemotherapy therapy within four weeks (six weeks for nitrosourea, mitomycin-C or any antibody therapy) of the start of imatinib administration
4. The subject has an Eastern Cooperative Oncology Group (ECOG) performance score of zero to two
5. Adequate end organ function, defined as the following:
5.1. Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)
5.2. Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) less than 2.5 x ULN
5.3. Creatinine less than 1.5 x ULN
5.4. Absolute neutrophil count (ANC) more than 1.5 x 10^9/L
5.5. Platelets more than 100 x 10^9/L
6. Female patients of childbearing potential must have negative pregnancy test within seven days before initiation of study drug dosing. Postmenopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to three months following discontinuation of study drug.
7. Life expectancy of more than three months (in the absence of any intervention)
8. The subject has voluntarily signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent prior to any study specific procedures
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
15
Participant exclusion criteria
1. The subject is less than five years free of another primary malignancy except:
1.1. If the other primary malignancy is not currently clinically significant nor requiring active intervention, or
1.2. If the other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ
2. The subject is with known brain metastases
3. The subject has received any other investigational agents within 28 days of first day of study drug dosing
4. The subject has a current history of a class three to four cardiovascular disability status in accordance with the New York Heart Association Functional Classification:
4.1. Class three is defined as marked limitation of physical activity, comfortable at rest, but less than ordinary activity causes fatigue or dyspnea
4.2. Class four is defined as being unable to carry on any physical activity without symptoms and symptoms are present even at rest. Also, if any physical activity is undertaken, symptoms are increased
5. Female patients who are pregnant or breast-feeding
6. Patient has another severe and/or life-threatening medical disease
7. The subject has an acute or known chronic liver disease (e.g., chronic active hepatitis, cirrhosis)
8. The subject has a known diagnosis of human immunodeficiency virus (HIV) infection
9. The subject has received chemotherapy within four weeks (six weeks for nitrosourea, mitomycin-C or any antibody therapy) prior to study entry
10. The subject had a major surgery within two weeks prior to study entry
11. The subject uses therapeutic anticoagulation with warfarins. Low-molecular weight heparin (e.g. Fragmin®) or heparin is permitted.
12. The subject with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent
Recruitment start date
11/07/2003
Recruitment end date
11/07/2006
Locations
Countries of recruitment
Netherlands
Trial participating centre
University Medical Centre Utrecht (UMCU)
Utrecht
3584 CX
Netherlands
Sponsor information
Organisation
University Medical Centre Utrecht (UMCU) (The Netherlands)
Sponsor details
P.O. Box 85500
Utrecht
3508 GA
Netherlands
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Industry
Funder name
Novartis Pharma B.V. (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
Results in http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17579194
Publication citations
-
Results
de Groot JW, Zonnenberg BA, van Ufford-Mannesse PQ, de Vries MM, Links TP, Lips CJ, Voest EE, A phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma., J. Clin. Endocrinol. Metab., 2007, 92, 9, 3466-3469, doi: 10.1210/jc.2007-0649.