Hereditary Thyroid Gland Medullary CarcinomaPhase 2NCT00390325
Sorafenib Tosylate in Treating Patients With Metastatic, Locally Advanced, or Recurrent Medullary Thyroid Cancer
A Phase 2 study testing Sorafenib Tosylate in people with Hereditary Thyroid Gland Medullary Carcinoma and Locally Advanced Thyroid Gland Medullary Carcinoma, run by National Cancer Institute (NCI) at 3 sites in United States.
Trial summary
This phase II trial studies how well sorafenib tosylate works in treating patients with medullary thyroid cancer that has spread to other parts of the body (metastatic), spread to the tissue surrounding the thyroid (locally advanced), or has returned after a period of improvement (recurrent). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hereditary Thyroid Gland Medullary Carcinoma, Locally Advanced Thyroid Gland Medullary Carcinoma, Multiple Endocrine Neoplasia Type 2A
- What is being tested?
- Sorafenib Tosylate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 3 sitesUnited States
- Study dates
- 3 Nov 2006to 22 Dec 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ELIGIBILITY CRITERIA SPECIFIC FOR ARM A
- Histologically confirmed medullary thyroid carcinoma under the clinical setting of inherited tumor syndromes, such as multiple endocrine neoplasia (MEN) 2A, MEN 2B, or familial medullary thyroid carcinoma (FMTC)
- ELIGIBILITY CRITERIA SPECIFIC FOR ARM B
- Histologically confirmed medullary thyroid carcinoma under the clinical setting of sporadic medullary thyroid carcinoma (MTC)
- ELIGIBILITY CRITERIA COMMON FOR ARMS A AND B
- Patients must have measurable disease
Show all 18Show fewer
- Metastatic and/or locally advanced or locally recurrent disease
- Oral or intravenous (IV) bisphosphonates therapy will be allowed for patients with bony metastasis at the investigator's discretion; bisphosphonate usage should be recorded if used since these agents may have anti-farnesyl transferase activity and may have some therapeutic effect in combination with sorafenib
- Life expectancy must be >= six months
- Patients must have an Eastern Cooperative Oncology Group performance status 0-2
- Leukocytes >= 2,000/uL (10 days prior to patient enrollment)
- Absolute neutrophil count >= 1,000/uL (10 days prior to patient enrollment)
- Platelets >= 100,000/uL (10 days prior to patient enrollment)
- Total bilirubin =< within 2 x upper limit of normal (10 days prior to patient enrollment)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< within 3 x upper limit of normal (10 days prior to patient enrollment)
- Serum creatinine within normal institutional limits OR creatinine clearance > 30 mL/min (by Cockcroft-Gault formula) (10 days prior to patient enrollment)
- The effects of sorafenib (BAY 43-9006) on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because kinase inhibitors are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 30 days after completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients who have had systemic anti-tumor therapy (such as chemotherapy, biologic modifiers or antiangiogenic therapy) within 4 weeks (6 weeks if nitrosourea or mitomycin chemotherapy) prior to study entry
- Patients who have had external beam radiation therapy within 1 week or if the adverse events associated with radiation are not resolved to grade 1 or less prior to study entry
- Prior therapy with sorafenib (BAY 43-9006), ZD 6474 or AMG-706
- Patients currently receiving any other tumor-specific therapy for thyroid cancer or investigational therapy; patients receiving adjuvant hormonal therapy for a second primary (such as breast cancer or prostate cancer) are allowed to participate as far as there are no known drug interactions
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib (BAY 43-9006)
- Patients unable to swallow sorafenib tablets (e.g. any condition that impairs patient's ability to swallow pills)
Show all 12Show fewer
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients with any evidence of a bleeding diathesis
- Patients actively receiving anticoagulation with therapeutic intent; prophylactic anticoagulation (i.e. low dose warfarin) or venous or arterial access devices is allowed provided that the prothrombin time (PT), international normalized ratio (INR) or partial thromboplastin time (PTT) are normal
- Pregnant women or women who are breast-feeding are excluded from this study because sorafenib (BAY 43-9006) is an investigational agent and teratogenicity has not been evaluated yet; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sorafenib (BAY 43-9006), breastfeeding should be discontinued if the mother is treated with sorafenib (BAY 43-9006)
- Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with sorafenib (BAY 43-9006); patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy
- Patients taking the cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin or St. John's wort due to potential drug interactions with sorafenib
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Duke University Medical Center
Durham, North Carolina, 27710
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Phase II Study of Sorafenib (BAY 43-9006) in Patients With Metastatic Medullary Thyroid Carcinoma
This phase II trial studies how well sorafenib tosylate works in treating patients with medullary thyroid cancer that has spread to other parts of the body (metastatic), spread to the tissue surrounding the thyroid (locally advanced), or has returned after a period of improvement (recurrent). Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess objective response rate of sorafenib tosylate (sorafenib [BAY 43-9006]) in metastatic medullary thyroid carcinoma in setting of inherited tumor syndromes, such as multiple endocrine neoplasia (MEN) 2A, MEN 2B, or familial medullary thyroid carcinoma (FMTC).
II. To assess objective response rate of sorafenib (BAY 43-9006) in sporadic metastatic medullary thyroid carcinoma.
SECONDARY OBJECTIVES:
- To assess toxicity of sorafenib (BAY 43-9006) in patients with metastatic medullary thyroid carcinoma.
II. Measure serum tumor markers calcitonin and carcinoembryonic antigen (CEA) pre-, during, and post-treatment to correlate with disease response.
III. Correlate nuclear medicine functional imaging (fludeoxyglucose F 18 [F-18 fluorodeoxyglucose] positron emission tomography [PET] scan) data obtained at pre-, during, and post-treatment with tumor response.
IV. Correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data obtained at pre-, during, and post-treatment with changes in tumor permeability and vascularity with tumor response.
- Perform pharmacogenomic studies on procured peripheral blood mononuclear cells (PBMCs) if clinical responses are observed.
VI. To correlate between the degree of retrovirus-associated sequence (Ras)-mitogen-activated protein kinase (MAPK) signaling inhibition and vascular endothelial growth factor (VEGF) expression in the tumor and clinical response.
VII. To correlate between the presence and type of ret proto-oncogene (RET) gene defects in tumor and clinical response.
OUTLINE:
Patients receive sorafenib tosylate orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity.
- Conditions
- Hereditary Thyroid Gland Medullary Carcinoma, Locally Advanced Thyroid Gland Medullary Carcinoma, Multiple Endocrine Neoplasia Type 2A, Multiple Endocrine Neoplasia Type 2B, Recurrent Thyroid Gland Medullary Carcinoma, Sporadic Thyroid Gland Medullary Carcinoma
- Being tested
- Sorafenib Tosylate
- Medical subject headings
- Familial medullary thyroid carcinoma, Multiple Endocrine Neoplasia Type 2a, Multiple Endocrine Neoplasia Type 2b, Carcinoma, Medullary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sorafenib TosylateDrug
Also called BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (sorafenib tosylate) | Experimental | Patients receive sorafenib tosylate PO BID in the absence of disease progression or unacceptable toxicity. Receives: Drug: Sorafenib Tosylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate of Sorafenib Tosylate in Metastatic Medullary Thyroid Carcinoma in Setting of Inherited Tumor Syndromes as Well as in Setting of Sporadic Medullary Thyroid Cancer
Measured using MRI scans. Determined using Response Evaluation Criteria in Solid Tumors/World Health Organization response criteria. 95% confidence interval will be calculated to estimate the frequency of response.
Measured: Up to 4 weeks after last dose of sorafenib tosylate
Secondary outcomes (9)
Number of Patients With Decreased Calcitonin Levels
Identifying the number of patients with decreased calcitonin levels
Measured: Up to 4 weeks after last dose of sorafenib tosylate
Patient With Decreased Carcinoembryonic Antigen (CEA) Levels
Identify the number of patients with decreased Carcinoembryonic Antigen (CEA) levels
Measured: Up to 4 weeks after last dose of sorafenib tosylate
Percent of Baseline Dynamic-Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) Exchange Rate Constant (Kep)
Median decrease in exchange rate Kep in index lesions
Measured: Up to 4 weeks after last dose of sorafenib tosylate
Degree of Ras-MAPK Signaling Inhibition in the Tumor
Identify the number of patients with degree of Ras-MAPK signaling inhibition
Measured: Up to 4 weeks after last dose of sorafenib tosylate
Degree of Vascular Endothelial Growth Factor (VEGF) Expression in the Tumor
Correlated with clinical response.
Measured: Up to 4 weeks after last dose of sorafenib tosylate
Standardized Uptake Value (SUV Max) as Measured by Fludeoxyglucose F-18 Positron Emission Tomography (PET)
Identify the median SUV at baseline and 8 week follow up as measured by Fludeoxyglucose F-18 Positron Emission Tomography (PET).
Measured: Up to 4 weeks after last dose of sorafenib tosylate
Number of Patients With Toxicity, Graded Using the Revised National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0
Toxicities were graded for patients using the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Measured: Up to 4 weeks after last dose of sorafenib tosylate
Number of Participants With Ret Proto-Oncogene (RET) Gene Defects in the Tumor
Percent of patients with RET mutations
Measured: Baseline
Selected Polymorphisms of Genes Influencing Sorafenib Tosylate Metabolism and/or Resistance Genes That May Predict Response or Toxicity
Changes will be correlated with toxicity and clinical response to therapy.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2006 (estimated)
- Study start3 Nov 2006
- Primary completion30 Jan 2017
- Study completion22 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hereditary Thyroid Gland Medullary CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Bhavana Konda, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00390325
- Sponsor's protocol ID
- NCI-2009-00196
- Other IDs
- NCI-2009-00196, 2006C0050, NCI-7609, CDR0000507441, OSU 06054 / IRB 2006C0050, 7609, 7609, N01CM00070
- Status last verified
- Jan 2024
- First submitted
- 18 Oct 2006
- Last updated
- 6 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Sorafenib (BAY 43-9006) in Patients With Metastatic Medullary Thyroid Carcinoma
- ClinicalTrials.gov ID
- NCT00390325
- Acronym / sponsor ID
- NCI-2009-00196
- Conditions
- Hereditary Thyroid Gland Medullary Carcinoma, Locally Advanced Thyroid Gland Medullary Carcinoma, Multiple Endocrine Neoplasia Type 2A, Multiple Endocrine Neoplasia Type 2B, Recurrent Thyroid Gland Medullary Carcinoma, Sporadic Thyroid Gland Medullary Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 3 Nov 2006 (actual)
- Primary completion
- 30 Jan 2017 (actual)
- Study completion
- 22 Dec 2022 (actual)
- First posted
- 19 Oct 2006 (estimated)
- Results
- Posted 21 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well sorafenib tosylate works in treating patients with medullary thyroid cancer that has spread to other parts of the body (metastatic), spread to the tissue surrounding the thyroid (locally advanced), or has returned after a period of improvement (recurrent). Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
Detailed description
PRIMARY OBJECTIVES:
- To assess objective response rate of sorafenib tosylate (sorafenib [BAY 43-9006]) in metastatic medullary thyroid carcinoma in setting of inherited tumor syndromes, such as multiple endocrine neoplasia (MEN) 2A, MEN 2B, or familial medullary thyroid carcinoma (FMTC).
II. To assess objective response rate of sorafenib (BAY 43-9006) in sporadic metastatic medullary thyroid carcinoma.
SECONDARY OBJECTIVES:
- To assess toxicity of sorafenib (BAY 43-9006) in patients with metastatic medullary thyroid carcinoma.
II. Measure serum tumor markers calcitonin and carcinoembryonic antigen (CEA) pre-, during, and post-treatment to correlate with disease response.
III. Correlate nuclear medicine functional imaging (fludeoxyglucose F 18 [F-18 fluorodeoxyglucose] positron emission tomography [PET] scan) data obtained at pre-, during, and post-treatment with tumor response.
IV. Correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data obtained at pre-, during, and post-treatment with changes in tumor permeability and vascularity with tumor response.
- Perform pharmacogenomic studies on procured peripheral blood mononuclear cells (PBMCs) if clinical responses are observed.
VI. To correlate between the degree of retrovirus-associated sequence (Ras)-mitogen-activated protein kinase (MAPK) signaling inhibition and vascular endothelial growth factor (VEGF) expression in the tumor and clinical response.
VII. To correlate between the presence and type of ret proto-oncogene (RET) gene defects in tumor and clinical response.
OUTLINE:
Patients receive sorafenib tosylate orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (sorafenib tosylate) | Experimental | Drug: Sorafenib TosylatePatients receive sorafenib tosylate PO BID in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- ELIGIBILITY CRITERIA SPECIFIC FOR ARM A
- Histologically confirmed medullary thyroid carcinoma under the clinical setting of inherited tumor syndromes, such as multiple endocrine neoplasia (MEN) 2A, MEN 2B, or familial medullary thyroid carcinoma (FMTC)
- ELIGIBILITY CRITERIA SPECIFIC FOR ARM B
- Histologically confirmed medullary thyroid carcinoma under the clinical setting of sporadic medullary thyroid carcinoma (MTC)
- ELIGIBILITY CRITERIA COMMON FOR ARMS A AND B
Key exclusion criteria (12 listed)
- Patients who have had systemic anti-tumor therapy (such as chemotherapy, biologic modifiers or antiangiogenic therapy) within 4 weeks (6 weeks if nitrosourea or mitomycin chemotherapy) prior to study entry
- Patients who have had external beam radiation therapy within 1 week or if the adverse events associated with radiation are not resolved to grade 1 or less prior to study entry
- Prior therapy with sorafenib (BAY 43-9006), ZD 6474 or AMG-706
- Patients currently receiving any other tumor-specific therapy for thyroid cancer or investigational therapy; patients receiving adjuvant hormonal therapy for a second primary (such as breast cancer or prostate cancer) are allowed to participate as far as there are no known drug interactions
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib (BAY 43-9006)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sorafenib TosylateAlso: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenibGiven PO | Drug | Treatment (sorafenib tosylate) |
Primary outcome
Objective Response Rate of Sorafenib Tosylate in Metastatic Medullary Thyroid Carcinoma in Setting of Inherited Tumor Syndromes as Well as in Setting of Sporadic Medullary Thyroid Cancer
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Measured using MRI scans. Determined using Response Evaluation Criteria in Solid Tumors/World Health Organization response criteria. 95% confidence interval will be calculated to estimate the frequency of response.
9 secondary outcomes
Number of Patients With Decreased Calcitonin Levels
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Patient With Decreased Carcinoembryonic Antigen (CEA) Levels
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Percent of Baseline Dynamic-Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) Exchange Rate Constant (Kep)
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Degree of Ras-MAPK Signaling Inhibition in the Tumor
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Degree of Vascular Endothelial Growth Factor (VEGF) Expression in the Tumor
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Standardized Uptake Value (SUV Max) as Measured by Fludeoxyglucose F-18 Positron Emission Tomography (PET)
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Number of Patients With Toxicity, Graded Using the Revised National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Number of Participants With Ret Proto-Oncogene (RET) Gene Defects in the Tumor
Time frame: Baseline
Selected Polymorphisms of Genes Influencing Sorafenib Tosylate Metabolism and/or Resistance Genes That May Predict Response or Toxicity
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Hereditary Thyroid Gland Medullary Carcinoma
Active, not recruitingPhase 2
Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
Adrenal Cortical Carcinoma, Alveolar Soft Part Sarcoma
RecruitingObservational study
Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients
Neuroendocrine Neoplasm, Neuroendocrine Neoplasm of Gastrointestinal Tract
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bhavana Konda principal investigator
Ohio State University Comprehensive Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sorafenib Tosylate in people with Hereditary Thyroid Gland Medullary Carcinoma and Locally Advanced Thyroid Gland Medullary Carcinoma, run by National Cancer Institute (NCI) at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate of Sorafenib Tosylate in Metastatic Medullary Thyroid Carcinoma in Setting of Inherited Tumor Syndromes as Well as in Setting of Sporadic Medullary Thyroid Cancer (time frame: Up to 4 weeks after last dose of sorafenib tosylate). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2024.