Efficacy and Safety Study of Sorafenib to Treat Advanced Medullary Thyroid Carcinoma (SUMMIT)
Primary Purpose
Medullary Thyroid Carcinoma
Status
Withdrawn
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Sorafenib
Sponsored by
About this trial
This is an interventional treatment trial for Medullary Thyroid Carcinoma focused on measuring Medullary Thyroid Carcinoma, Sorafenib, Efficacy
Eligibility 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
Sites / Locations
- University Hospital Ulm, Clinic for Nuclear Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Sorafenib tablets
Placebo tablets
Arm Description
Oral administration of Sorafenib tablets, 400 mg bid, until disease progression or unacceptable toxicity
Oral administration of Placebo tablets until disease progression, afterwards continuation with Sorafenib at the discretion of the investigator
Outcomes
Primary Outcome Measures
Progression Free Survival (PFS)
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
Time to Progression (TPP)
The average TTP in the Sorafenib group and the Placebo group will be compared.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01736878
Brief Title
Efficacy and Safety Study of Sorafenib to Treat Advanced Medullary Thyroid Carcinoma
Acronym
SUMMIT
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 Type
Interventional
2. Study Status
Record Verification Date
May 2013
Overall Recruitment Status
Withdrawn
Why Stopped
Study was withdrawn due to unanticipated hassle in patient recruitment.
Study Start Date
October 2012 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
April 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eanm Research Ltd
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Medullary Thyroid Carcinoma
Keywords
Medullary Thyroid Carcinoma, Sorafenib, Efficacy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sorafenib tablets
Arm Type
Experimental
Arm Description
Oral administration of Sorafenib tablets, 400 mg bid, until disease progression or unacceptable toxicity
Arm Title
Placebo tablets
Arm Type
Placebo Comparator
Arm Description
Oral administration of Placebo tablets until disease progression, afterwards continuation with Sorafenib at the discretion of the investigator
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
from the date of randomisation until the date of radiological or biochemical progression or death. An average of 9 months is assumed.
Secondary Outcome Measure Information:
Title
Time to Progression (TPP)
Description
The average TTP in the Sorafenib group and the Placebo group will be compared.
Time Frame
from the date of randomisation until the date of confirmed radiological or biochemical progression. An average of 9 months is assumed.
Other Pre-specified Outcome Measures:
Title
Overall Survival (OS)
Description
The proportion of surviving patients in the Sorafenib group and the Placebo group will be compared.
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
University Hospital Ulm, Clinic for Nuclear Medicine
City
Ulm
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
D-89081
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety Study of Sorafenib to Treat Advanced Medullary Thyroid Carcinoma
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