Thyroid NeoplasmsPhase 2NCT01838642
Ponatinib for Advanced Medullary Thyroid Cancer
A Phase 2 study testing Ponatinib in people with Thyroid Neoplasms, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial summary
Background: Medullary thyroid cancer (MTC) represents 5% of thyroid cancers and presents as a hereditary (25% of cases) or sporadic (75% of cases) neuroendocrine malignancy. MTC arises from the parafollicular C-cells of the thyroid. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Thyroid Neoplasms
- What is being tested?
- Ponatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to Jan 2016
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of localized or metastatic unresectable medullary thyroid cancer (MTC). The histological diagnosis of MTC must be confirmed on review of submitted tumor tissue by the Laboratory of Pathology in the National Cancer Institute
- Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral computed tomography (CT) scan.
- Disease amenable to biopsy and agree to undergo biopsy for molecular analysis
- The last dose of previous therapy targeting rearranged during transfection (RET) kinase must be given at least 4 weeks prior to the first dose of ponatinib.
- Previous treatment with cytotoxic chemotherapy, immunotherapy, or radiotherapy are permitted, if the last dose was given at least 4 weeks prior to the first dose of ponatinib
- Patient must have failed (progressed on or been intolerant of) prior treatment with cabozantinib and vandetanib.
Show all 20Show fewer
- Age greater than or equal to 18 years old
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
- Normal organ and marrow function as defined below:
- Leukocytes greater than or equal to microL
- Absolute neutrophil count 1,500/microL
- Platelet count greater than or equal to 100,000 microL
- Total bilirubin < 1.5 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase(SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) < 2.5 times institutional ULN or < 5 times ULN if liver involvement
- Prothrombin Time < 1.5 times ULN
- Creatinine < 1.5 times ULN
- Lipase less than or equal to 1.5 times ULN
- Negative pregnancy test for women of childbearing potential. The effects of ponatinib on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Normal QT interval corrected (Fridericia) (QTcF) on screening electrocardiogram (ECG) evaluation, defined as QTcF of less than or equal to 450 ms in males or less than or equal to 470 ms in females.
- Ability to understand and the willingness to sign a written informed consent document and follow the guidelines of the clinical protocol including visits to National Cancer Institute (NCI), Bethesda, Maryland for treatment and follow up visits.
Who cannot join
- Patients who are receiving any other investigational agent.
- Patients with brain metastases or spinal cord compression unless they completed radiation therapy greater than or equal to 4 weeks prior to the first dose of ponatinib and are stable without steroids or anti-convulsant therapy for greater than or equal to 10 days.
- Medications that are known to be associated with Torsades de Pointes.
- Uncontrolled hypertension (systolic blood pressure > 150 or diastolic blood pressure > 100
- Significant or active cardiovascular disease, specifically including but not restricted to:
- History of myocardial infarction
Show all 21Show fewer
- History of atrial or ventricular arrhythmia
- Unstable angina within 6 months prior to first dose of ponatinib
- History of congestive heart failure
- Left ventricular ejection fraction fraction (LVEF) less than lower limit of normal
- History of peripheral arterial occlusive disease
- History of cerebrovascular accident or transient ischemic attack
- Venous thromboembolism including deep venous thrombosis or pulmonary embolism within 6 months prior to enrollment
- A history of pancreatitis or alcohol abuse
- Uncontrolled hypertriglyceridemia (> 450 mg/dL)
- Major surgery (with the exception of minor surgical procedures, such as catheter placement or tumor biopsy) within 28 days prior to the first dose of ponatinib
- Ongoing or active infection including known history of human immunodeficiency virus [HIV], hepatitis B virus [HBV], or hepatitis C virus[HCV]. Testing for these viruses is not required in the absence of a history of infection.
- Suffer from any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the safety of the study drug
- Evidence of a bleeding diathesis that cannot be corrected with standard therapy or factor replacement
- Presence of another primary malignancy within the past 2 years (except for nonmelanoma skin cancer or cervical cancer in situ. Prior prostate cancer is also permitted if prostatic specific antigen (PSA) is now undetectable.)
- Pregnant or lactating
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase II Study of Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer
Background:
- Medullary thyroid cancer (MTC) represents 5% of thyroid cancers and presents as a hereditary (25% of cases) or sporadic (75% of cases) neuroendocrine malignancy.
- MTC arises from the parafollicular C-cells of the thyroid.
- Germline mutations in the rearranged during transfection (RET) proto-oncogene occur in virtually all of hereditary MTC cases, and somatic RET mutations occur in 50% of sporadic cases.
- Drugs targeting RET kinase such as vandetanib and cabozantinib have shown efficacy in the treatment of advanced or metastatic MTC, however, more effective RET inhibitors are needed for previously untreated patients as well as patients who have become refractory to other molecular targeted therapeutics (MTTs).
- Ponatinib, a drug that is Food and Drug Administration (FDA) approved as a therapy for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), is a potent inhibitor of RET kinase.
Read more
Primary Objective:
-To determine the objective overall response rate (complete response [CR] + partial response
[PR] by Response Evaluation Criteria in Solid Tumors (RECIST) to ponatinib in the treatment of patients with advanced or metastatic MTC previously treated with cabozantinib and vandetanib who: 1) have tumors with RET mutations and 2) have tumors without RET mutations.
Eligibility:
- Patients must have histologically confirmed, unresectable, locally advanced or metastatic MTC, with measurable disease by RECIST criteria.
- Patients must have disease amenable to biopsy and be willing to undergo biopsy for molecular analysis, and also have adequate archival material from their thyroidectomy or from a tumor biopsy obtained prior to beginning any systemic therapy.
- Patients must have failed or been intolerant to prior treatment with both cabozantinib and vandetanib.
- The last dose of prior systemic therapy must be more than 28 days prior to the first dose of ponatinib
- Radiation therapy is permitted if the last treatment was received more than 28 days prior to the first dose of ponatinib.
Design:
- Open label phase II trial with 2 treatment groups:
- RET mutation positive MTC, previously treated with vandetanib and cabozantinib
- RET mutation negative MTC, previously treated with vandetanib and cabozantinib
- Patients will receive ponatinib 30 mg orally daily until disease progression or until the development of intolerable side effects.
- Tumor response will be assessed by RECIST 1.1 criteria at 8 weeks and then every 12 weeks thereafter. After one year on study, tumor response will be assessed every 16 weeks.
- Patients will have a biopsy of their MTC for molecular analysis prior to initiating treatment with ponatinib. Patients will also have a biopsy of their MTC at the time of tumor progression, should that occur.
Read the detailed description
Background:
- Medullary thyroid cancer (MTC) represents 5% of thyroid cancers and presents as a hereditary (25% of cases) or sporadic (75% of cases) neuroendocrine malignancy.
- MTC arises from the parafollicular C-cells of the thyroid.
- Germline mutations in the rearranged during transfection (RET) proto-oncogene occur in virtually all of hereditary MTC cases, and somatic RET mutations occur in 50% of sporadic cases.
- Drugs targeting RET kinase such as vandetanib and cabozantinib have shown efficacy in the treatment of advanced or metastatic MTC, however, more effective RET inhibitors are needed for previously untreated patients as well as patients who have become refractory to other molecular targeted therapeutics (MTTs).
- Ponatinib, a drug that is Food and Drug Administration (FDA) approved as a therapy for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), is a potent inhibitor of RET kinase.
Primary Objective:
-To determine the objective overall response rate (complete response [CR] + partial response [PR] by Response Evaluation Criteria in Solid Tumors (RECIST) to ponatinib in the treatment of patients with advanced or metastatic MTC previously treated cabozantinib and vandetanib who: 1) have tumors with RET mutations and 2) have tumors without RET mutations.
Eligibility:
- Patients must have histologically confirmed, unresectable, locally advanced or metastatic MTC, with measurable disease by RECIST criteria.
- Patients must have disease amenable to biopsy and be willing to undergo biopsy for molecular analysis, and also have adequate archival material from their thyroidectomy or from a tumor biopsy obtained prior to beginning any systemic therapy.
- Patients must have failed or been intolerant to prior treatment with both cabozantinib and vandetanib.
- The last dose of prior systemic therapy must be more than 28 days prior to the first dose of ponatinib.
- Radiation therapy is permitted if the last treatment was received more than 28 days prior to the first dose of ponatinib.
Design:
- Open label phase II trial with 2 treatment groups:
- RET mutation positive MTC, previously treated with vandetanib and cabozantinib
- RET mutation negative MTC, previously treated with vandetanib and cabozantinib
- Patients will receive ponatinib 30 mg orally daily until disease progression or until the development of intolerable side effects.
- Tumor response will be assessed by RECIST 1.1 criteria at 8 weeks and then every 12 weeks thereafter. After one year on study, tumor response will be assessed every 16 weeks.
- Patients will have a biopsy of their MTC for molecular analysis prior to initiating treatment with ponatinib. Patients will also have a biopsy of their MTC at the time of tumor progression, should that occur.
- Conditions
- Thyroid Neoplasms
- Being tested
- Ponatinib
- Keywords
- Monoclonal Antibody, AP24534, RET Mutation Positive, RET Mutation Negative, RET Inhibitor
- Medical subject headings
- Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PonatinibDrug
Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.
| Study group | Role | What they receive |
|---|---|---|
| RET mutation positive participants | Active comparator | Rearranged during transfection (RET) mutation positive Receives: Drug: Ponatinib |
| RET mutation negative participants | Active comparator | Rearranged during transfection (RET) mutation negative Receives: Drug: Ponatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate.
Defined as the percentage of participants with a best response (complete response (CR) + partial response (PR)) recorded from the start of the treatment until disease progression/recurrence assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (Whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Measured: 2-4 months
Secondary outcomes (7)
Progression Free Survival
Progression free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Measured: 2-4 months
Number of Participants With Adverse Events
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Measured: 17 months and 19 days
Molecular Differences in Advanced Medullary Thyroid Cancer (MTC)
Compare the molecular profile of tumor deoxyribonucleic acid (DNA) prior to treatment with the molecular profile at the time of progression. Prior to the first dose of ponatinib and at time of progression, subjects were to undergo a biopsy of the primary tumor or any metastatic site for analysis of tumor DNA for rearranged during transfection (RET) or rat sarcoma (RAS) mutation. Progression is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as at least a 20% decrease in the sum of diameters of target lesions, taking as reference the smallest sum on study.
Measured: Prior to the first dose of ponatinib
Changes in Serum Levels of MTC Tumor Markers Calcitonin (CTN) and Its Relation With Clinical Response
Responders are those subjects with a best biomarker response of complete response (CR) or partial response (PR) and who achieve a clinical response of CR or PR assessed by the following criteria. Biomarker: complete response (CR) is normalization (</= upper limit of normal (ULN)) of CTN (i.e., normal <10 pg/mL) following treatment, confirmed with a repeat CTN level at least 4 weeks apart. Partial response (PR) is a >/=50% decrease in the CTN level relative to baseline level, confirmed with a repeat CTN level at least 4 weeks apart. Clinical: complete response (CR) is an average of 0-2 formed stools per day for a period of at least 4 weeks. Partial response (PR) is a >50% decrease in the average stool frequency relative to baseline and a change in stool consistency from watery to loose (partially formed) for a period of at least 4 weeks.
Measured: Baseline to 4 weeks
Objective Response to Ponatinib
Objective response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (Whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. Stable disease (SD) is neither shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Measured: up to 4 cycles of treatment with ponatinib
Changes in Serum Levels of MTC Tumor Markers Carcinoemybryonic Antigen (CEA) and Its Relation With Clinical Response
Responders are those subjects with a best biomarker response of complete response (CR) or partial response (PR) and who achieve a clinical response of CR or PR assessed by the following criteria. Biomarker: complete response (CR) is normalization (</= upper limit of normal (ULN)) of CTN (i.e., normal 0-2.5 mcg/L) following treatment, confirmed with a repeat CEA level at least 4 weeks apart. Partial response (PR) is a >/=50% decrease in the CEA level relative to baseline level, confirmed with a repeat CEA level at least 4 weeks apart. Clinical: complete response (CR) is an average of 0-2 formed stools per day for a period of at least 4 weeks. Partial response (PR) is a >50% decrease in the average stool frequency relative to baseline and a change in stool consistency from watery to loose (partially formed) for a period of at least 4 weeks.
Measured: Baseline to 4 weeks
Overall Survival
Overall survival is defined as the time between the first day of treatment to the day of disease progression.
Measured: up to 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 Apr 2013 (estimated)
- Study startMar 2013
- Primary completionDec 2015
- Study completionJan 2016
Why it stopped: Recruiting halted prematurely and will not resume. New study to open soon.
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Thyroid NeoplasmsStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, James Gulley, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- James Gulley, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01838642
- Sponsor's protocol ID
- 130108
- Other IDs
- 13-C-0108
- Status last verified
- Dec 2016
- First submitted
- 20 Apr 2013
- Last updated
- 15 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Lakhani VT, You YN, Wells SA. The multiple endocrine neoplasia syndromes. Annu Rev Med. 2007;58:253-65. doi: 10.1146/annurev.med.58.100305.115303.
PubMed 17037976Modigliani E, Cohen R, Campos JM, Conte-Devolx B, Maes B, Boneu A, Schlumberger M, Bigorgne JC, Dumontier P, Leclerc L, Corcuff B, Guilhem I. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d'etude des tumeurs a calcitonine. Clin Endocrinol (Oxf). 1998 Mar;48(3):265-73. doi: 10.1046/j.1365-2265.1998.00392.x.
PubMed 9578814Moley JF, DeBenedetti MK. Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg. 1999 Jun;229(6):880-7; discussion 887-8. doi: 10.1097/00000658-199906000-00016.
PubMed 10363903
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer
- ClinicalTrials.gov ID
- NCT01838642
- Acronym / sponsor ID
- 130108
- Conditions
- Thyroid Neoplasms
- Keywords
- Monoclonal Antibody, AP24534, RET Mutation Positive, RET Mutation Negative, RET Inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruiting halted prematurely and will not resume. New study to open soon.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2013
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 24 Apr 2013 (estimated)
- Results
- Posted 17 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Medullary thyroid cancer (MTC) represents 5% of thyroid cancers and presents as a hereditary (25% of cases) or sporadic (75% of cases) neuroendocrine malignancy.
- MTC arises from the parafollicular C-cells of the thyroid.
- Germline mutations in the rearranged during transfection (RET) proto-oncogene occur in virtually all of hereditary MTC cases, and somatic RET mutations occur in 50% of sporadic cases.
- Drugs targeting RET kinase such as vandetanib and cabozantinib have shown efficacy in the treatment of advanced or metastatic MTC, however, more effective RET inhibitors are needed for previously untreated patients as well as patients who have become refractory to other molecular targeted therapeutics (MTTs).
- Ponatinib, a drug that is Food and Drug Administration (FDA) approved as a therapy for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), is a potent inhibitor of RET kinase.
Primary Objective:
-To determine the objective overall response rate (complete response [CR] + partial response
[PR] by Response Evaluation Criteria in Solid Tumors (RECIST) to ponatinib in the treatment of patients with advanced or metastatic MTC previously treated with cabozantinib and vandetanib who: 1) have tumors with RET mutations and 2) have tumors without RET mutations.
Eligibility:
- Patients must have histologically confirmed, unresectable, locally advanced or metastatic MTC, with measurable disease by RECIST criteria.
- Patients must have disease amenable to biopsy and be willing to undergo biopsy for molecular analysis, and also have adequate archival material from their thyroidectomy or from a tumor biopsy obtained prior to beginning any systemic therapy.
- Patients must have failed or been intolerant to prior treatment with both cabozantinib and vandetanib.
- The last dose of prior systemic therapy must be more than 28 days prior to the first dose of ponatinib
- Radiation therapy is permitted if the last treatment was received more than 28 days prior to the first dose of ponatinib.
Design:
- Open label phase II trial with 2 treatment groups:
- RET mutation positive MTC, previously treated with vandetanib and cabozantinib
- RET mutation negative MTC, previously treated with vandetanib and cabozantinib
- Patients will receive ponatinib 30 mg orally daily until disease progression or until the development of intolerable side effects.
- Tumor response will be assessed by RECIST 1.1 criteria at 8 weeks and then every 12 weeks thereafter. After one year on study, tumor response will be assessed every 16 weeks.
- Patients will have a biopsy of their MTC for molecular analysis prior to initiating treatment with ponatinib. Patients will also have a biopsy of their MTC at the time of tumor progression, should that occur.
Detailed description
Background:
- Medullary thyroid cancer (MTC) represents 5% of thyroid cancers and presents as a hereditary (25% of cases) or sporadic (75% of cases) neuroendocrine malignancy.
- MTC arises from the parafollicular C-cells of the thyroid.
- Germline mutations in the rearranged during transfection (RET) proto-oncogene occur in virtually all of hereditary MTC cases, and somatic RET mutations occur in 50% of sporadic cases.
- Drugs targeting RET kinase such as vandetanib and cabozantinib have shown efficacy in the treatment of advanced or metastatic MTC, however, more effective RET inhibitors are needed for previously untreated patients as well as patients who have become refractory to other molecular targeted therapeutics (MTTs).
- Ponatinib, a drug that is Food and Drug Administration (FDA) approved as a therapy for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), is a potent inhibitor of RET kinase.
Primary Objective:
-To determine the objective overall response rate (complete response [CR] + partial response [PR] by Response Evaluation Criteria in Solid Tumors (RECIST) to ponatinib in the treatment of patients with advanced or metastatic MTC previously treated cabozantinib and vandetanib who: 1) have tumors with RET mutations and 2) have tumors without RET mutations.
Eligibility:
- Patients must have histologically confirmed, unresectable, locally advanced or metastatic MTC, with measurable disease by RECIST criteria.
- Patients must have disease amenable to biopsy and be willing to undergo biopsy for molecular analysis, and also have adequate archival material from their thyroidectomy or from a tumor biopsy obtained prior to beginning any systemic therapy.
- Patients must have failed or been intolerant to prior treatment with both cabozantinib and vandetanib.
- The last dose of prior systemic therapy must be more than 28 days prior to the first dose of ponatinib.
- Radiation therapy is permitted if the last treatment was received more than 28 days prior to the first dose of ponatinib.
Design:
- Open label phase II trial with 2 treatment groups:
- RET mutation positive MTC, previously treated with vandetanib and cabozantinib
- RET mutation negative MTC, previously treated with vandetanib and cabozantinib
- Patients will receive ponatinib 30 mg orally daily until disease progression or until the development of intolerable side effects.
- Tumor response will be assessed by RECIST 1.1 criteria at 8 weeks and then every 12 weeks thereafter. After one year on study, tumor response will be assessed every 16 weeks.
- Patients will have a biopsy of their MTC for molecular analysis prior to initiating treatment with ponatinib. Patients will also have a biopsy of their MTC at the time of tumor progression, should that occur.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RET mutation positive participants | Active comparator | Drug: PonatinibRearranged during transfection (RET) mutation positive |
| RET mutation negative participants | Active comparator | Drug: PonatinibRearranged during transfection (RET) mutation negative |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Diagnosis of localized or metastatic unresectable medullary thyroid cancer (MTC). The histological diagnosis of MTC must be confirmed on review of submitted tumor tissue by the Laboratory of Pathology in the National Cancer Institute
- Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral computed tomography (CT) scan.
- Disease amenable to biopsy and agree to undergo biopsy for molecular analysis
- The last dose of previous therapy targeting rearranged during transfection (RET) kinase must be given at least 4 weeks prior to the first dose of ponatinib.
- Previous treatment with cytotoxic chemotherapy, immunotherapy, or radiotherapy are permitted, if the last dose was given at least 4 weeks prior to the first dose of ponatinib
Key exclusion criteria (21 listed)
- Patients who are receiving any other investigational agent.
- Patients with brain metastases or spinal cord compression unless they completed radiation therapy greater than or equal to 4 weeks prior to the first dose of ponatinib and are stable without steroids or anti-convulsant therapy for greater than or equal to 10 days.
- Medications that are known to be associated with Torsades de Pointes.
- Uncontrolled hypertension (systolic blood pressure > 150 or diastolic blood pressure > 100
- Significant or active cardiovascular disease, specifically including but not restricted to:
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 |
|---|---|---|
| PonatinibPonatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting. | Drug | RET mutation negative participants, RET mutation positive participants |
Primary outcome
Overall Response Rate.
Time frame: 2-4 months
Defined as the percentage of participants with a best response (complete response (CR) + partial response (PR)) recorded from the start of the treatment until disease progression/recurrence assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (Whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
7 secondary outcomes
Progression Free Survival
Time frame: 2-4 months
Number of Participants With Adverse Events
Time frame: 17 months and 19 days
Molecular Differences in Advanced Medullary Thyroid Cancer (MTC)
Time frame: Prior to the first dose of ponatinib
Changes in Serum Levels of MTC Tumor Markers Calcitonin (CTN) and Its Relation With Clinical Response
Time frame: Baseline to 4 weeks
Objective Response to Ponatinib
Time frame: up to 4 cycles of treatment with ponatinib
Changes in Serum Levels of MTC Tumor Markers Carcinoemybryonic Antigen (CEA) and Its Relation With Clinical Response
Time frame: Baseline to 4 weeks
Overall Survival
Time frame: up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17037976Lakhani VT, You YN, Wells SA. The multiple endocrine neoplasia syndromes. Annu Rev Med. 2007;58:253-65. doi: 10.1146/annurev.med.58.100305.115303.
- Background: PubMed 9578814Modigliani E, Cohen R, Campos JM, Conte-Devolx B, Maes B, Boneu A, Schlumberger M, Bigorgne JC, Dumontier P, Leclerc L, Corcuff B, Guilhem I. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d'etude des tumeurs a calcitonine. Clin Endocrinol (Oxf). 1998 Mar;48(3):265-73. doi: 10.1046/j.1365-2265.1998.00392.x.
- Background: PubMed 10363903Moley JF, DeBenedetti MK. Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg. 1999 Jun;229(6):880-7; discussion 887-8. doi: 10.1097/00000658-199906000-00016.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Thyroid Gland Carcinoma
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.
James Gulley, M.D. principal investigator
National Cancer Institute (NCI)
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 Ponatinib in people with Thyroid Neoplasms, run by National Institutes of Health Clinical Center (CC) 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 20 inclusion and 21 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 15 Feb 2017. 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 17 Mar 2016). 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 Rate. (time frame: 2-4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01838642, which also lists 3 linked publications.
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 15 Feb 2017.