A phase II study to investigate the effect of Glivec® (imatinib mesylate, formerly known as STI571) in patients with inoperable medullary thyroid carcinoma

ISRCTN	ISRCTN13256080
DOI	https://doi.org/10.1186/ISRCTN13256080
Secondary identifying numbers	CSTI571BNL07; METC 03-044

Submission date: 23/02/2007
Registration date: 23/02/2007
Last edited: 20/12/2007

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Contact information

Dr B A Zonnenberg
Scientific

University Medical Centre Utrecht (UMCU)
Department of Medical Oncology
Heidelberglaan 100
Utrecht
3584 CX
Netherlands

Phone	+31 (0)30 250 6308
Email	B.Zonnenberg@umcutrecht.nl

Study information

Study design	Observational phase II study
Primary study design	Observational
Secondary study design	Single-centre
Study setting(s)	Other
Study type	Treatment
Scientific title
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(s)	Ethics approval received from the local medical ethics committee
Condition	Medullary thyroid carcinoma
Intervention	Oral treatment with 600 - 800 mg imatinib daily.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Imatinib mesylate (Glivec®)
Primary outcome measure	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 study start date	11/07/2003
Overall study end date	11/07/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	15
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 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

Study participating centre

University Medical Centre Utrecht (UMCU)

Utrecht
3584 CX
Netherlands

Sponsor information

University Medical Centre Utrecht (UMCU) (The Netherlands)
Hospital/treatment centre

P.O. Box 85500
Utrecht
3508 GA
Netherlands

Website	http://www.umcutrecht.nl/zorg/
"ROR"	https://ror.org/04pp8hn57

Funders

Funder type

Industry

Novartis Pharma B.V. (The Netherlands)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	Results	01/09/2007		Yes	No