Efficacy and Safety Study of Sorafenib to Treat Advanced Medullary Thyroid Carcinoma (SUMMIT)

Study Description

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Brief Summary:

The purpose of his study is to evaluate the efficacy and safety of Sorafenib versus placebo in subjects with locally advanced medullary thyroid cancer (MTC). The primary study objective is to compare the Progression-free Survival (PFS) of the Sorafenib treatment group with the placebo treatment group in patients with advanced MTC.

Condition or disease	Intervention/treatment	Phase
Medullary Thyroid Carcinoma	Drug: Sorafenib	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	0 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	October 2012
Actual Primary Completion Date :	April 2013
Actual Study Completion Date :	April 2013

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Sorafenib tablets; Oral administration of Sorafenib tablets, 400 mg bid, until disease progression or unacceptable toxicity	Drug: Sorafenib
Placebo Comparator: Placebo tablets; Oral administration of Placebo tablets until disease progression, afterwards continuation with Sorafenib at the discretion of the investigator	Drug: Sorafenib

Outcome Measures

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Primary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: from the date of randomisation until the date of radiological or biochemical progression or death. An average of 9 months is assumed. ]
   The proportion of patients with PFS in the Sorafenib group and the Placebo group will be compared by log rank test and Kaplan-Meier plot.

Secondary Outcome Measures :

1. Time to Progression (TPP) [ Time Frame: from the date of randomisation until the date of confirmed radiological or biochemical progression. An average of 9 months is assumed. ]
   The average TTP in the Sorafenib group and the Placebo group will be compared.

Other Outcome Measures:

1. Overall Survival (OS) [ Time Frame: from the date of randomisation until the date of death due to any cause. Final assessment at the end of study after approximately 36 months. ]
   The proportion of surviving patients in the Sorafenib group and the Placebo group will be compared.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Inpatient or outpatient ≥ 18 years of age
• Histologically confirmed medullary thyroid carcinoma
• Recurrent or persistent local disease and/or distant metastases
• No more than one prior line of systemic therapy
• Best available supportive care to control (endocrine) symptoms
• At least one defined lesion in CT or MRI evaluable for Response Evaluation Criteria in Solid Tumors (RECIST v1.1), or at least one defined lesion in CT or MRI not evaluable by RECIST in combination with elevated tumour markers
• Progression within previous 12 months
• Hb > 8g/dl, white blood cells (WBC) >3.000 cells/mm³ (ANC > 1.500 cells/mm³), platelets > 100.000 cells/mm³, bilirubin < 2mg/dl, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN)
• Performance status: WHO ≤ 2; Karnofsky index ≥ 50%
• Sufficient renal function (creatinin <1.5 mg/dl and creatinin clearance > 30ml/min)
• International normalized ratio (INR) and partial thromboplastin time (PTT) < 1.5 x ULN
• No acute infections
• Staging studies (MRT or CT and Calcitonin or CEA) completed within four weeks of protocol randomisation
• Women of childbearing potential with negative serum pregnancy test
• Women and men of childbearing potential using adequate contraception
• Signed and dated written informed consent

Exclusion Criteria:

• Unresolved toxicity (i.e. neurotoxicity) attributed to any prior therapy higher than National Cancer Institute-Common Toxicity Criteria for Adverse Effects (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
• Current participation in another investigational trial
• Patients with significant cardiovascular disease
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy other than beta-blockers or digoxin
• Congenital long corrected QT interval (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, 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
• 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
• Pregnant or breast-feeding patients
• Patients with uncontrolled infections
• Known HIV infection or infection with hepatitis B or C
• Immunosuppression
• Subjects with seizure disorder requiring medication • 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

Contacts and Locations

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Locations

Germany
University Hospital Ulm, Clinic for Nuclear Medicine
Ulm, Baden-Wuerttemberg, Germany, D-89081

Sponsors and Collaborators

Eanm Research Ltd

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Eanm Research Ltd
ClinicalTrials.gov Identifier:	NCT01736878 History of Changes
Other Study ID Numbers:	EARL-2; 2011-006250-90 ( EudraCT Number )
First Posted:	November 29, 2012
Last Update Posted:	May 17, 2013
Last Verified:	May 2013

Keywords provided by Eanm Research Ltd:

Medullary Thyroid Carcinoma; Sorafenib; Efficacy

Additional relevant MeSH terms:

Carcinoma; Thyroid Diseases; Thyroid Neoplasms; Carcinoma, Neuroendocrine; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal	Adenocarcinoma; Neoplasms, Nerve Tissue; Sorafenib; Niacinamide; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Vitamin B Complex; Vitamins; Micronutrients; Growth Substances; Physiological Effects of Drugs