Randomized double-blind placebo controlled Phase II study to evaluate the efficacy and safety of Sorafenib treatment in patients with advanced (recurrent, persistent and/or metastasizing) medullary thyroid carcinoma (SUMMIT).
- Conditions
- Advanced (recurrent, persistent and/or metastasizing) medullary thyroid carcinomaTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-006250-90-DE
- Lead Sponsor
- EANM Forschungs GmbH / EANM Research Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 110
• Patient must be = 18 years of age when signing the informed consent form
• Histologically confirmed medullary thyroid carcinoma (C-cell thyroid carcinoma)
• Recurrent or persistent local disease and/or distant metastases not suitable for local curative treatment (surgery or radiation therapy) assessed by Investigator
• No more than one prior line of systemic therapy (including no more than 1 prior line with a targeted drug, e.g. kinase inhibitor)
• Best available supportive care to control (endocrine) symptoms according to current standards established for at least 8 weeks before study entry
• At least one defined lesion in CT or MRI evaluable for RECIST (v1.1), no older than 42 days from planned treatment start, or at least one defined lesion in CT or MRI not evaluable by RECIST in combination with elevated tumour markers with minimum initial levels of 150 pg/ml for calcitonin or 5 x UILN for CEA (e.g., in case of bone metastases)
• Progression within previous 12 months (according to RECIST 1.1 criteria or tumour marker progression (calcitonin or CEA referred to normal Reference Ranges from Site Lab) can be used as a basis for the assessment of disease progression); tumour marker doubling time must be no longer than 12 months (30) and a minimum initial level of 150 pg/ml for calcitonin or 5 x UILN for CEA, respectively, need to be present. The tumour marker doubling time should be estimated using the calculator at the ATA-website: http://www.thyroid.org/professionals/calculators/CDTC.php
• Hb > 8g/dl, WBC >3.000 cells/mm³ (ANC > 1.500 cells/mm³), platelets > 100.000 cells/mm³, bilirubin < 2mg/dl, Alanine aminotransaminase (ALT) and Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (referred to normal Reference Ranges from Site Lab)
• Performance status: WHO = 2; Karnofsky index = 50%
• Patients should have sufficient renal function, as determined by serum creatinine <1.5 mg/dl and CrCL > 30ml/min
• PT-INR and PTT < 1.5 x upper limit of normal (referred to normal Reference Ranges from Site Lab) [Patients who are being therapeutically anticoagulated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists]
• No acute infections at the time of therapy initiation
• Staging studies (MRT or CT and Calcitonin or CEA) completed within four weeks of protocol randomisation
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
• Women and men of childbearing potential must agree to use adequate contraception (barrier method of birth control) from signing of the informed consent form until at least 30 days after the last study drug administration (men for at least 3 months after last administration of study medication)
• Patient is able to understand the study procedures, voluntarily agrees to participate in the study and has given a signed and dated written informed consent prior to study participation.
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 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 110
• Unresolved toxicity (i.e. neurotoxicity) attributed to any prior therapy higher than NCI-CTCAE (version 4) Grade 2 (excluding cases of alopecia)
• Patients with history of allergic or hypersensitivity reaction to study drug or placebo or their excipients or with a history of allergic reactions attributed to compounds with similar composition to any of the study drug or placebo.
• Current participation in another investigational trial
• Patients with significant cardiovascular disease, such as myocardial infarction < 6 months, unstable coronary artery disease (anginal symptoms at rest), new-onset angina within 3 months before randomization, or chronic heart failure (New York Heart Association grade III or IV)
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy other than beta-blockers or digoxin
• Congenital long QTc syndrome, history of drug induced QTc prolongation, or QTc interval unmeasurable or more than 450 ms
• Abnormal serum electrolytes such as potassium, magnesium and calcium
• Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg, despite optimal management
• Major surgery, open biopsy, or significant traumatic injury within 30 days prior to randomization
• Non-healing wound, ulcer, or bone fracture
• Evidence or history of bleeding diathesis or coagulopathy disorder
• Hemorrhage/bleeding event = Grade 3 within 3 months prior to first dose of study drug
• Thrombotic or embolic events including transient ischemic attacks within the past 6 months
• Subjects with symptomatic brain metastases or Subjects with brain metastases under corticosteroid treatment. Previous or concurrent cancer that is distinct in primary site or histology from thyroid cancer within 5 years prior to randomization EXCEPT cervical cancer in situ, treated basal cell carcinoma and superficial bladder tumours [Ta (Non invasive tumour), Tis (Carcinoma in situ) and T1 (Tumour invades lamina propria)]
• Pregnant or breast-feeding patients
• Patients with uncontrolled infections
• Known human immunodeficiency virus (HIV) infection or infection with hepatitis B or C
• Immunosuppression
• Subjects with seizure disorder requiring medication (such as steroids or anti¬epileptics)
• Subjects undergoing renal dialysis
• Substance abuse, medical, psychological or social conditions that may interfere with the subject’s participation in the study or evaluation of the study results
• Any malabsorption condition
• Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method