Thyroid CancerPhase 2NCT00115739
Trial Evaluating Gleevec in Patients With Anaplastic Thyroid Carcinoma
A Phase 2 study testing Imatinib in people with Thyroid Cancer, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
Anaplastic thyroid cancers are rare, aggressive tumors. Standard treatment options include surgery and chemoradiation. Few treatment options are available once metastases develop. Recent data suggest that Imatinib (Gleevec) may be advantageous in this patient population. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thyroid Cancer
- What is being tested?
- Imatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2004to Aug 2010
- 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
- Patients with histologically confirmed anaplastic thyroid carcinoma, who have measurable disease.
- Patients with brain metastases are eligible if they have been stable for at least six weeks post-radiation therapy.
- Age 18 years, male or female.
- Karnofsky performance status (KPS) of > 70%.
- Life expectancy of at least 12 weeks.
- Hematologic: ANC 1,500 mm3, hemoglobin 8.0 g/dl, platelets 100,000/mm3
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- Normal serum calcium level within normal limits for the institution documented within 14 days prior to registration.
- All patients (including those with liver metastases) must have adequate hepatic function as defined by a serum bilirubin 1.5 x the institutional upper limit of normal (ULN), and ALT and AST <2.5 x ULN, obtained within 14 days prior to registration.
- Patients must have a serum creatinine less than 1.5 x the institutional upper limits of normal (adjusted for age) within 14 days of registration.
- Women of childbearing potential must have a negative pregnancy test at baseline, prior to receiving any study drug. (Pregnant or lactating patients are excluded.)
- Patients of reproductive potential must practice effective contraception while on study and for at least six months after receiving the last dose of study drug.
- All patients must sign an informed consent prior to enrollment.
- No prior history of non-thyroid malignancy, except adequately treated skin cancer or in situ cervical carcinoma or any other cancer in complete remission for at least two years.
- Prior chemotherapy, chemoradiation, radiation therapy, or surgery must have been completed at least 28 days prior to registration, and all toxicities must have resolved. Patients who have been treated with nitrosourea or mitomycin C must be off of these drugs for at least 6 weeks prior to registration.
- Patients must be able to take oral medications.
Who cannot join
- Anaplastic thyroid cancer that does not overexpress PDGF receptors or c-Abl by immunohistochemistry
- Any medical or psychiatric illness which, in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment regimen.
- No concurrent radiotherapy (to the primary tumor) or chemotherapy may be given to the patient during the administration of the study drug.
- Pregnant or lactating women, women of childbearing potential with either a positive pregnancy test (PPT) at baseline, or sexually active females not using reliable contraceptive methods while on study and for at least six months after chemotherapy. (Postmenopausal women must have been amenorrheic for least 12 months to be considered of non-childbearing potential).
- Sexually active males not using reliable contraceptive methods while on the study and for at least six months after chemotherapy.
- Patients with malabsorption syndromes will be excluded.
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- Serious concurrent infections.
- Patients who have had previous organ allografts will be excluded.
- Prisoners.
- Patients with chronic liver disease (i.e chronic active hepatitis and cirrhosis).
- Patients with a known diagnosis of human immunodeficiency virus (HIV) infection.
- Patients who have had major surgery within 2 weeks of study entry.
- Patients with grade III/IV cardiac problems as defined by the New York Heart Association Criteria (i.e. congestive heart failure, myocardial infarction within 6 months of study entry).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Cancer Center
Ann Arbor, Michigan, 48109
About this study
Official title: Phase II Trial Evaluating Gleevec (Imatinib Mesylate Formerly Known as STI571) in Patients With Anaplastic Thyroid Cancer
Anaplastic thyroid cancers are rare, aggressive tumors. Standard treatment options include surgery and chemoradiation. Few treatment options are available once metastases develop. Recent data suggest that Imatinib (Gleevec) may be advantageous in this patient population. Patients who have been treated for anaplastic thyroid cancer with chemoradiation or surgery who develop recurrent or metastatic disease outside of the field of radiation are eligible. Patients will be treated with Imatinib 400 mg two times a day for eight weeks, followed by radiologic assessment. Patients will be treated until disease progression or a complete response is obtained.
Read the detailed description
Anaplastic thyroid carcinomas (ATC) are high grade neoplasms, which account for approximately 2% to 5% of primary malignant thyroid tumors but more than 50% of thyroid cancer deaths. Because therapies for anaplastic thyroid carcinoma are very limited with even early stage disease, new approaches for treating this devastating cancer are needed. Recently, imatinib mesylate (Gleevec®), formerly known as STI571, has been approved for the treatment of chronic myelogenous leukemia and for treatment of gastrointestinal stromal tumors, expressing the c-Kit tyrosine kinase. Imatinib is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor, c-Kit, and inhibits PDGF- and SCF-mediated cellular events. Recent data suggest that many if not most, anaplastic thyroid cancers express PDGF receptors, and that these receptors are functional. Additional preclinical work from Japan demonstrates that c-Abl is overexpressed in p53 mutated/deficient anaplastic thyroid carcinoma cell lines and that select inhibition of c-Abl activity by STI571 has a dramatic cytostatic effect in these cells.
Additional data suggest that many, if not most, anaplastic thyroid cancers express PDGF receptors, and that these receptors are functional. Since activation of PDGF receptors is associated with the growth of other tumors and c-Abl is overexpressed in p53-mutated anaplastic thyroid carcinoma cell lines, it seems appropriate to test Gleevec as a therapy for patients with anaplastic thyroid cancer. The specific hypothesis to be tested is that anaplastic thyroid cancers that overexpress PDGF receptors or Abl will respond to Gleevec therapy. The lack of any accepted efficacious therapies for anaplastic thyroid cancer, the poor prognosis of this cancer, and the relatively low toxicity of Gleevec justify this proposed trial.
Patients with anaplastic thyroid carcinoma who are status post best local control with surgery/chemoradiation, who have measurable disease outside their previous field of radiation, are eligible.
The Primary Objective of this study is:
- To determine the overall response (complete and partial response) rates of patients with anaplastic thyroid cancer treated with Gleevec at the first response assessment (i.e. 8 weeks following the start of Gleevec), following best local control with surgery or radiation/chemoradiation.
The Secondary Objectives include:
- To measure the grade III/IV toxicities experienced by patients with anaplastic thyroid cancer who are treated with Gleevec.
- To determine the time to obtain complete or partial responses in patients with anaplastic thyroid cancer treated with Gleevec, following best local control with surgery or radiation/chemoradiation.
Treatment Plan:
Patients will be treated with Imatinib (Gleevec) 400 mg two times a day for eight weeks after which radiologic imaging will be obtained to assess response. Patients who attained a complete response will be treated with four additional weeks of Imatinib. Patients who attain a partial response or stable disease will be treated until a complete response is attained, or until disease progression. All patients with progression of disease will be taken off the study. Patients continuing on the study, will undergo radiologic imaging every eight weeks following their initial response assessment. All patients will be followed until death.
- Conditions
- Thyroid Cancer
- Being tested
- Imatinib
- Keywords
- Anaplastic Thyroid Cancer
- Medical subject headings
- Thyroid Neoplasms, Thyroid Carcinoma, Anaplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImatinibDrug
Also called Gleevec
Imatinib 400 mg capsules were administered twice daily with food for 4 week cycles.
| Study group | Role | What they receive |
|---|---|---|
| Imatinib | Experimental | Patients will be treated with Imatinib (Gleevec) 400 mg two times a day for eight weeks after which radiologic imaging will be obtained to assess response. Patients who attained a complete response will be treated with four additional weeks of Imatinib. Patients who attain a partial response or stable disease will be treated until a complete response is attained, or until disease progression. All patients with progression of disease will be taken off the study. Patients continuing on the study, will undergo radiologic imaging every eight weeks following their initial response assessment. All patients will be followed until death. Receives: Drug: Imatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response (Complete and Partial Response) Rate at 8 Weeks
The number of patients with Complete Response (CR), Partial Response (PR) and Stable Disease (SD) were determined at 8 weeks.
Measured: 8 weeks
Secondary outcomes (3)
Rate of Grade 3, Grade 4 and Grade 5 Toxicities Experienced by Patients With Anaplastic Thyroid Cancer Who Are Treated With Gleevec
Number of grade 3, grade 4 and grade 5 toxicities experienced by patients with anaplastic thyroid cancer who are treated with Gleevec.
Measured: Up to 30 days post treatment
6 Month Progression Free Survival Rate
The percentage of patients with 6 months progression-free survival was estimated. Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, the appearance of new lesions, or the significant clinical deterioration related to progression of patient's disease.
Measured: 6 months
6 Month Survival Rate
The percentage of patients still alive at 6 months was estimated.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2005 (estimated)
- Study startFeb 2004
- Primary completionMay 2008
- Study completionAug 2010
Why it stopped: Study was closed early due to slow accrual
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 Thyroid CancerStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe 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
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francis (Frank) Worden, University of Michigan Rogel Cancer Center
- Investigators
- Francis P Worden, MD, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00115739
- Sponsor's protocol ID
- UMCC 2003-044
- Other IDs
- IRBMED number 2003-0701
- Status last verified
- Mar 2014
- First submitted
- 23 Jun 2005
- Last updated
- 21 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial Evaluating Gleevec (Imatinib Mesylate Formerly Known as STI571) in Patients With Anaplastic Thyroid Cancer
- ClinicalTrials.gov ID
- NCT00115739
- Acronym / sponsor ID
- UMCC 2003-044
- Conditions
- Thyroid Cancer
- Keywords
- Anaplastic Thyroid Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was closed early due to slow accrual
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Feb 2004
- Primary completion
- May 2008 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 24 Jun 2005 (estimated)
- Results
- Posted 21 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Anaplastic thyroid cancers are rare, aggressive tumors. Standard treatment options include surgery and chemoradiation. Few treatment options are available once metastases develop. Recent data suggest that Imatinib (Gleevec) may be advantageous in this patient population. Patients who have been treated for anaplastic thyroid cancer with chemoradiation or surgery who develop recurrent or metastatic disease outside of the field of radiation are eligible. Patients will be treated with Imatinib 400 mg two times a day for eight weeks, followed by radiologic assessment. Patients will be treated until disease progression or a complete response is obtained.
Detailed description
Anaplastic thyroid carcinomas (ATC) are high grade neoplasms, which account for approximately 2% to 5% of primary malignant thyroid tumors but more than 50% of thyroid cancer deaths. Because therapies for anaplastic thyroid carcinoma are very limited with even early stage disease, new approaches for treating this devastating cancer are needed. Recently, imatinib mesylate (Gleevec®), formerly known as STI571, has been approved for the treatment of chronic myelogenous leukemia and for treatment of gastrointestinal stromal tumors, expressing the c-Kit tyrosine kinase. Imatinib is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor, c-Kit, and inhibits PDGF- and SCF-mediated cellular events. Recent data suggest that many if not most, anaplastic thyroid cancers express PDGF receptors, and that these receptors are functional. Additional preclinical work from Japan demonstrates that c-Abl is overexpressed in p53 mutated/deficient anaplastic thyroid carcinoma cell lines and that select inhibition of c-Abl activity by STI571 has a dramatic cytostatic effect in these cells.
Additional data suggest that many, if not most, anaplastic thyroid cancers express PDGF receptors, and that these receptors are functional. Since activation of PDGF receptors is associated with the growth of other tumors and c-Abl is overexpressed in p53-mutated anaplastic thyroid carcinoma cell lines, it seems appropriate to test Gleevec as a therapy for patients with anaplastic thyroid cancer. The specific hypothesis to be tested is that anaplastic thyroid cancers that overexpress PDGF receptors or Abl will respond to Gleevec therapy. The lack of any accepted efficacious therapies for anaplastic thyroid cancer, the poor prognosis of this cancer, and the relatively low toxicity of Gleevec justify this proposed trial.
Patients with anaplastic thyroid carcinoma who are status post best local control with surgery/chemoradiation, who have measurable disease outside their previous field of radiation, are eligible.
The Primary Objective of this study is:
- To determine the overall response (complete and partial response) rates of patients with anaplastic thyroid cancer treated with Gleevec at the first response assessment (i.e. 8 weeks following the start of Gleevec), following best local control with surgery or radiation/chemoradiation.
The Secondary Objectives include:
- To measure the grade III/IV toxicities experienced by patients with anaplastic thyroid cancer who are treated with Gleevec.
- To determine the time to obtain complete or partial responses in patients with anaplastic thyroid cancer treated with Gleevec, following best local control with surgery or radiation/chemoradiation.
Treatment Plan:
Patients will be treated with Imatinib (Gleevec) 400 mg two times a day for eight weeks after which radiologic imaging will be obtained to assess response. Patients who attained a complete response will be treated with four additional weeks of Imatinib. Patients who attain a partial response or stable disease will be treated until a complete response is attained, or until disease progression. All patients with progression of disease will be taken off the study. Patients continuing on the study, will undergo radiologic imaging every eight weeks following their initial response assessment. All patients will be followed until death.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imatinib | Experimental | Drug: ImatinibPatients will be treated with Imatinib (Gleevec) 400 mg two times a day for eight weeks after which radiologic imaging will be obtained to assess response. Patients who attained a complete response will be treated with four additional weeks of Imatinib. Patients who attain a partial response or stable disease will be treated until a complete response is attained, or until disease progression. All patients with progression of disease will be taken off the study. Patients continuing on the study, will undergo radiologic imaging every eight weeks following their initial response assessment. All patients will be followed until death. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients with histologically confirmed anaplastic thyroid carcinoma, who have measurable disease.
- Patients with brain metastases are eligible if they have been stable for at least six weeks post-radiation therapy.
- Age 18 years, male or female.
- Karnofsky performance status (KPS) of > 70%.
- Life expectancy of at least 12 weeks.
Key exclusion criteria (13 listed)
- Anaplastic thyroid cancer that does not overexpress PDGF receptors or c-Abl by immunohistochemistry
- Any medical or psychiatric illness which, in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment regimen.
- No concurrent radiotherapy (to the primary tumor) or chemotherapy may be given to the patient during the administration of the study drug.
- Pregnant or lactating women, women of childbearing potential with either a positive pregnancy test (PPT) at baseline, or sexually active females not using reliable contraceptive methods while on study and for at least six months after chemotherapy. (Postmenopausal women must have been amenorrheic for least 12 months to be considered of non-childbearing potential).
- Sexually active males not using reliable contraceptive methods while on the study and for at least six months after chemotherapy.
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 |
|---|---|---|
| ImatinibAlso: GleevecImatinib 400 mg capsules were administered twice daily with food for 4 week cycles. | Drug | Imatinib |
Primary outcome
Overall Response (Complete and Partial Response) Rate at 8 Weeks
Time frame: 8 weeks
The number of patients with Complete Response (CR), Partial Response (PR) and Stable Disease (SD) were determined at 8 weeks.
3 secondary outcomes
Rate of Grade 3, Grade 4 and Grade 5 Toxicities Experienced by Patients With Anaplastic Thyroid Cancer Who Are Treated With Gleevec
Time frame: Up to 30 days post treatment
6 Month Progression Free Survival Rate
Time frame: 6 months
6 Month Survival Rate
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Francis P Worden, MD principal investigator
University of Michigan Rogel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Imatinib in people with Thyroid Cancer, run by University of Michigan Rogel Cancer Center at 1 site 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 15 inclusion and 13 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: stopped early, as of the sponsor's last update on 21 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 Apr 2014). 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?
Overall Response (Complete and Partial Response) Rate at 8 Weeks (time frame: 8 weeks). 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 21 Apr 2014.