Phase II Trial of Sorafenib (Nexavar) in Patients With Advanced Thyroid Cancer

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT00654238
• Collaborator: (none)
• Enrollment: 59
• Location: 1
• Arm: 1
• Duration (Months): 60.9
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The goal of this study is to determine the activity of sorafenib in patients with advanced (metastatic or recurrent) thyroid cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Differentiated Thyroid Cancer; Metastatic Poorly Differentiated Thyroid Cancer; Metastatic Anaplastic Thyroid Cancer; Metastatic Medullary Thyroid Cancer	Drug: sorafenib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of BAY 43-9006 in Patients With Metastatic Thyroid Cancer
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 This is a single arm study.	Drug: sorafenib; 400mg PO BID daily; Other Names: Nexavar (Bayer)

Outcome Measures

Primary Outcome Measures

1. To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

1. Median Progression Free Survival in Patients Receiving BAY 43-9006 (Sorafenib). [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months]

   This is the result of the Kaplan Meier analysis of all patients treated with sorafenib

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have histologically confirmed thyroid cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.

• Patients may have received multiple treatments of radioactive iodine, one prior biologic treatment, and at least half of the patients will have had no prior chemotherapy for metastatic disease. At least 3 weeks must have elapsed since prior treatment.

• Measurable disease defined as at least one malignant lesion that can be accurately and serially measured in at least one dimension (longest diameter to be recorded), using a caliper (diameter > 10 mm) for superficial cutaneous disease, or using contrast-enhanced CT or spiral CT (diameter > 20 mm) for visceral or nodal/soft tissue disease.

• ECOG performance status < 2 (Appendix 1).

• Life expectancy greater than 3 months.

• Adequate organ function that has been determined within 7 days prior to enrollment, defined as:Leucocyte count > 3,000/uL; Absolute neutrophil count (ANC) > 1,500/mm3, platelets > 100,000/mm3, and hemoglobin > 9 g/dl; Serum creatinine < 1.5 times ULN, or 24-hour creatinine clearance > 75 cc/min. (Note: creatinine clearance need not be determined if the baseline serum creatinine is within normal limits); Serum bilirubin < 1.5 times ULN; serum glutamyloxaloacetic transaminase (SGOT) < 2.5 ULN; alkaline phosphatase < 2.5 times ULN; PT-INR/PTT < 1.5 x upper limit of normal.

• Intellectual, emotional, and physical ability to comply with oral medication.

• Ability to understand and the willingness to sign a written informed consent

• Patients with disease accessible for biopsy will be preferentially selected for participation in the study. Accessible disease includes lymph node metastases.

• Female patients of child-bearing potential must have a negative pregnancy test within 14 days before initiation of study drug dosing. Post-menopausal women must be amenorrheic for at least 12 months to be considered non-child-bearing potential. Male and female patients of reproductive potential must agree to use adequate contraception (i.e. hormonal or barrier method of birth control). throughout the study and for 3 months after the study.

Exclusion Criteria:

• Significant medical disease including: uncontrolled congestive heart failure; active symptoms of coronary artery disease, uncontrolled seizure disorder; active infection; uncontrolled diabetes mellitus; requirement for chronic corticosteroid treatment; requirement for concurrent immunosuppressive drug(s); active autoimmune disease.

• Organ allografts.

• Known HIV-infection (HIV testing is not required for participation).

• Pregnancy or lactation. Women of childbearing potential and sexually active males must be advised to take precautions to prevent pregnancy during treatment

• History of second cancer (except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for five or more years).

• Use of any experimental therapy within 3 weeks prior to baseline evaluations done prior to enrollment.

• Patients with carcinomatous meningitis are excluded from the study.

• Excluded therapies and medications, previous and concomitant:Anticancer chemotherapy or immunotherapy during the study or within 4 weeks prior to the first dose of the study drug; Radiotherapy for the treatment of a symptomatic (e.g. bone metastasis) as clinically indicated is allowed as long as it is not evidence of progressive disease (see 4.5.2); -Biological response modifiers, such as G-CSF, within 3 week prior to study entry. (G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction); Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study; Investigational drug therapy outside of this trial during or within 4 weeks prior the screening assessment; Use of ketoconazole, itraconazole, and ritonavir; Use of carbamazepine, phenytoin, phenobarbital; Previous exposure to a Ras pathway inhibitor (including herceptin, EGFr inhibitors, farnesyl transferase inhibitors or MEK inhibitors); Use of grapefruit juice products; Use of cyclosporin;

• Pregnant or breast feeding.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania - Abramson Comprehensive Cancer Center	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania

Investigators

• Principal Investigator: Marcia S Brose, MD PhD, Unviersity of Pennsylvania - Abramson Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Marcia Brose, Associate Professor, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00654238
• Other Study ID Numbers: 802861; UPCC 03305; NCT00601783
• First Posted: Apr 7, 2008
• Last Update Posted: Nov 18, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by Marcia Brose, Associate Professor, University of Pennsylvania: Thyroid Cancer; Anaplastic; Medullary; sorafenib
• Additional relevant MeSH terms: Thyroid Neoplasms; Thyroid Carcinoma, Anaplastic; Thyroid Diseases; Sorafenib

Study Results

Participant Flow

Arm/Group Title	Sorafenib
Arm/Group Description	This is a single arm study. sorafenib: 400mg PO BID daily
Period Title: Overall Study
STARTED	59
COMPLETED	55
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Sorafenib
Arm/Group Description	This is a single arm study. sorafenib: 400mg PO BID daily
Overall Participants	55
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63
Sex: Female, Male (Count of Participants)
Female	27 49.1%
Male	28 50.9%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	55 100%
Histology subtype (Count of Participants)
DIfferentiated	44 80%
Poorly Differentiated	6 10.9%
Medullary	3 5.5%
Anaplastic	2 3.6%
ECOG Performance Status at Baseline (Count of Participants)
ECOG Performance Status 0	29 52.7%
ECOG Performance Status 1	26 47.3%

Outcome Measures

1. Primary Outcome

Title	To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma.
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Outcome Measure Data

Analysis Population Description

Responses were calculated by total enrolled to each group by histologic subtype.

Arm/Group Title	Sorafenib
Arm/Group Description	This is a single arm study. sorafenib: 400mg PO BID daily
Measure Participants	55
Complete Response	0 0%
Partial response	16 29.1%
Stable Disease	22 40%
Progressive Disease	1 1.8%
Not Evaluable for Response	5 9.1%
Complete Response	0 0%
Partial response	2 3.6%
Stable Disease	1 1.8%
Progressive Disease	1 1.8%
Not Evaluable for Response	2 3.6%
Complete Response	0 0%
Partial response	1 1.8%
Stable Disease	2 3.6%
Progressive Disease	0 0%
Not Evaluable for Response	0 0%
Complete Response	0 0%
Partial response	0 0%
Stable Disease	0 0%
Progressive Disease	1 1.8%
Not Evaluable for Response	1 1.8%

2. Secondary Outcome

Title	Median Progression Free Survival in Patients Receiving BAY 43-9006 (Sorafenib).
Description	This is the result of the Kaplan Meier analysis of all patients treated with sorafenib
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Outcome Measure Data

Analysis Population Description

Of the 59 patients that were consented, four patients were deemed ineligible as a result of inadequate CBC and the establishment of an alternative diagnosis resulting from secondary pathology review. Therefore the total number of patients analyzed going forward was 55.

Arm/Group Title	Progression Free Survival For Entire Study (55 Total Patients)
Arm/Group Description	This is based on Kaplan Meier estimate
Measure Participants	55
Median (95% Confidence Interval) [weeks]	77

Adverse Events

Time Frame	5 Years
Arm/Group Title	Sorafenib
Arm/Group Description	This is a single arm study. sorafenib: 400mg PO BID daily
All Cause Mortality
	Sorafenib
	Affected / at Risk (%)	# Events
Total	36/55 (65.5%)
Serious Adverse Events
	Sorafenib
	Affected / at Risk (%)	# Events
Total	4/55 (7.3%)
Blood and lymphatic system disorders
Deep Vein Thhrombosis	2/55 (3.6%)	2
Nervous system disorders
Cerebral Vascular Accident/Stroke	2/55 (3.6%)	2
Other (Not Including Serious) Adverse Events
	Sorafenib
	Affected / at Risk (%)	# Events
Total	43/55 (78.2%)
Gastrointestinal disorders
Diarrhea	29/55 (52.7%)	29
Stomatitis/Mucositis	18/55 (32.7%)	18
GI Discomfort	9/55 (16.4%)	9
Hepatic Lab Abnormalities	1/55 (1.8%)	1
General disorders
Fatigue	15/55 (27.3%)	15
Metabolism and nutrition disorders
Anorexia and Weight Loss	7/55 (12.7%)	7
Musculoskeletal and connective tissue disorders
Myalgia	11/55 (20%)	11
Skin and subcutaneous tissue disorders
Hand Foot Skin Reaction	43/55 (78.2%)	43
Rash	41/55 (74.5%)	41
Alopecia	25/55 (45.5%)	25
Squamous Cell Carcinoma of the Skin	8/55 (14.5%)	8
Vascular disorders
Hypertension	8/55 (14.5%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.