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

NCT01736878 | Withdrawn Phase 2 DMC

• 2 other identifiers: EARL-22011-006250-90
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Medullary Thyroid Carcinoma

Keywords

Medullary Thyroid Carcinoma; Sorafenib; Efficacy

Outcome Measures

Primary Outcomes (1)

• 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.

  from the date of randomisation until the date of radiological or biochemical progression or death. An average of 9 months is assumed.

Secondary Outcomes (1)

• Time to Progression (TPP)

  from the date of randomisation until the date of confirmed radiological or biochemical progression. An average of 9 months is assumed.

Other Outcomes (1)

• Overall Survival (OS)

  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.

Study Arms (2)

Sorafenib tablets

EXPERIMENTAL

Oral administration of Sorafenib tablets, 400 mg bid, until disease progression or unacceptable toxicity

Drug: Sorafenib

Placebo tablets

PLACEBO COMPARATOR

Oral administration of Placebo tablets until disease progression, afterwards continuation with Sorafenib at the discretion of the investigator

Drug: Sorafenib

Interventions

Sorafenib DRUG

Placebo tablets; Sorafenib tablets

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eanm Research Ltd: lead

Study Sites (1)

University Hospital Ulm, Clinic for Nuclear Medicine

Ulm, Baden-Wurttemberg, D-89081, Germany

Location

MeSH Terms

Conditions

Carcinoma, Medullary

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2012
• First Posted: November 29, 2012
• Study Start: October 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: May 17, 2013

Record last verified: 2013-05

Locations

DE (1)