Endometrial NeoplasmsNCT01888562
Ponatinib in the Treatment of FGFR Mutation Positive Recurrent or Persistent Endometrial Carcinoma
A study testing Ponatinib in people with Endometrial Neoplasms, run by Washington University School of Medicine.
Trial summary
To test the patient's cancerous tumor to see if it has a FGFR mutation and, if so, to see how their cancer responds to a treatment with the drug ponatinib as well as examine the side effects caused by ponatinib. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Neoplasms
- What is being tested?
- Ponatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2016to Jul 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have recurrent or persistent endometrial carcinoma which is refractory to curative therapy or established treatments. Histologic confirmation of the original primary tumor is required. Patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma.
- All patients must have measurable disease. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT, and MRI, or ≥ 10 mm when measured by spiral CT.
- Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1 (Section 11.1). Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
- Patients must have a documented FGFR2 activating mutation either on primary, recurrent or metastatic biopsy. Over 90% of FGFR2 mutations occur at 7 codons. Activating mutations are defined as the known FGFR2 hotspots at S252W, P253R, S373C, Y376C, C383R, N550K, N550H, K660E.
- Patients who have received one or two prior regimen must have a GOG Performance Status of 0, 1, or 2. Patients who have received three prior regimens must have a GOG Performance Status of 0 or 1.
- Patients must be ≥ 18 years of age.
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- Patients must be able to swallow tablets.
- Patients must have recovered from the effects of recent surgery, radiotherapy, or chemotherapy.
- Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated UTI).
- Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration.
- Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least three weeks prior to registration.
- Patients must have had at least one prior chemotherapeutic regimen for management of endometrial carcinoma. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer will be counted as a systemic chemotherapy regimen. Patients may have received prior anti-angiogenic compounds (i.e., bevacizumab).
- Patients are allowed to receive, but are not required to receive, up to two additional cytotoxic regimens for management of recurrent or persistent endometrial disease according to the following definition:
- Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa.
- Patients must have adequate bone marrow function defined as:
- Absolute neutrophil count (ANC) ≥ 1,500/mcl
- Platelets ≥ 100,000/mcl
- Hemoglobin > 9 g/dl
- Patients must have adequate renal function defined as:
- Creatinine ≤ 1.5 x institutional upper limit normal (ULN)
- Proteinuria must be ≤ 3+ by dipstick at baseline. If the urine dipstick is > 3+, a 24-hour protein level must be performed. The 24-hour protein level must be ≤ 3.5 g/24 hours.
- Patients must have adequate hepatic function defined as:
- Bilirubin ≤ 1.5 x ULN
- AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 2.5 x ULN
- Albumin ≥ 2.5 g/dl
- Patients must have adequate neurologic function defined as:
- Neuropathy (sensory and motor) ≤ grade 1
- Patients must have adequate blood coagulation parameters defined as:
- PT such that international normalized ratio (INR) is ≤ 1.5
- Patients on therapeutic warfarin are excluded from trial; anticoagulation with a heparin or heparin-like compound is permitted provided patient's PT INR is ≤ 1.5.
- Patients must be able to understand and willing to sign an approved informed consent and authorization permitting release of personal health information.
- Patients of childbearing potential must have a negative serum pregnancy test performed 48 hours prior to first dose and be practicing an effective form of contraception during the study and for at least 3 months after receiving the final treatment of ponatinib. Effective contraception is defined as hormonal or barrier method, or abstinence.
- Patients must have a baseline electrocardiogram completed prior to study entry with QTc ≤ 450 msec. Baseline ECG should be repeated if QTc is found to be > 450 msec. QTc must NOT be > 450 msec on both ECGs performed during the same visit.
Who cannot join
- Patients must not have had prior therapy with ponatinib or anti-FGFR (fibroblast growth factor receptor) therapy including brivanib, BIBF1120, and E7080.
- Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, localized cancer of the breast, and localized cancer of the head and neck, are excluded if there is any evidence of the other malignancy being present within the last five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
- Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last five years are excluded. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease.
- Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last five years are excluded. Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease.
- Patients must not be on required chronic anti-platelet therapy (aspirin >300 mg/day, or clopidogrel greater than or equal to 75mg/day).
- Patients must not have any gastrointestinal bleeding or any other hemorrhage/bleeding event ≥ grade 3 within 30 days prior to study entry.
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- Patients must not have a history of poor wound healing, non-healing ulcers or bone fractures within the last 3 months.
- Patients must not have uncontrolled or significant cardiovascular disease including:
- Myocardial infarction within 3 months
- Uncontrolled angina within 3 months
- Class III-IV New York Heart Association (NYHA) congestive heart failure (see Appendix B)
- Uncontrolled hypertension (systolic BP > 150 or diastolic BP > 100 mmHg for 24 hours) despite optimized anti-hypertensive therapy. BP must be below 150/100 mmHg at screening. Subjects with a history of hypertension who are receiving treatment with calcium channel blockers that are CYP3A4 inhibitors should be changed to an alternative antihypertensive medication before study entry
- History of stroke, TIA, or other CNS ischemic event
- Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
- Pre-therapy Left Ventricle Ejection Fraction (LVEF) ≤ 50%
- Valvular heart disease ≥ grade 2
- Patients must not have a serious uncontrolled medical disorder or active infection which would impair the ability of the subject to receive protocol therapy or whose control may be jeopardized by the complications of this therapy.
- Patients must not have any pre-existing thyroid abnormality with thyroid function that cannot be maintained in the institutional normal range with medication.
- Patients must not have hyponatremia (sodium < 130mEq/L).
- Patients must not have active/known HIV, Hepatitis B, or Hepatitis C.
- Patients must not have known brain metastases. Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurologic and other adverse events.
- Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biological composition to ponatinib or other agents used in this study.
- Patients must not be pregnant or nursing.
- Patients must not have untreated malabsorption syndrome.
- Patients must not have baseline serum potassium < 3.5 mmol/L (potassium supplementation may be given to restore the serum potassium above this level prior to study entry).
- Patients on therapeutic warfarin anticoagulation will be excluded. Patients converted to anticoagulation with a heparin compound will be allowed provided the PT INR is ≤ 1.5.
- Patients with:
- History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
- History of alcohol abuse
- History of uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)
- Women and Minorities
- Participating institutions will not exclude potential subjects from participating in this or any study solely on the basis of ethnic origin or socioeconomic status. Every attempt will be made to enter all eligible patients into this protocol and therefore address the study objectives in a patient population representative of the entire endometrial cancer population treated by participating institutions.
About this study
Official title: A Pilot Evaluation of Ponatinib (AP24534), a Potent Oral Pan-FGFR Inhibitor, in the Treatment of FGFR Mutation Positive Recurrent or Persistent Endometrial Carcinoma: a Multi-Institutional Study
To test the patient's cancerous tumor to see if it has a FGFR mutation and, if so, to see how their cancer responds to a treatment with the drug ponatinib as well as examine the side effects caused by ponatinib.
- Conditions
- Endometrial Neoplasms
- Being tested
- Ponatinib
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PonatinibDrug
Also called Iclusig™
Ponatinib 45 mg daily for 4 weeks (4 weeks equal one cycle)
| Study group | Role | What they receive |
|---|---|---|
| Ponatinib | Experimental | Ponatinib 45mg po daily for 4 weeks (4 weeks equal 1 cycle). Receives: Drug: Ponatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor responses (CR + PR)
Ponatinib in patients with recurrent or persistent endometrioid endometrial cancer (FGFR2 activating mutation positive)for tumor responses (CR + PR)
Complete Response (CR): 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): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: 6 months
Progression Free survival
Ponatinib in patients with recurrent or persistent endometrioid endometrial cancer (FGFR2 activating mutation positive) by evaluating 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: 6 months
Secondary outcomes (3)
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: 5.5 years
overall survival
Overall survival is define as date from time of initial treatment to date of death from any cause.
Measured: 5.5 years
Toxicity of Ponatinib
Frequency and severity as defined by CTCAE v 4.0
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2013 (estimated)
- Study startJan 2016
- Primary completionJul 2018 (estimated)
- Study completionJul 2023 (estimated)
Why it stopped: Could not obtain an IDE on the FGFR2 assay
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometrial NeoplasmsStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matthew Powell, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01888562
- Sponsor's protocol ID
- 201404024
- Status last verified
- Dec 2015
- First submitted
- 25 Jun 2013
- Last updated
- 18 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Evaluation of Ponatinib (AP24534), a Potent Oral Pan-FGFR Inhibitor, in the Treatment of FGFR Mutation Positive Recurrent or Persistent Endometrial Carcinoma: a Multi-Institutional Study
- ClinicalTrials.gov ID
- NCT01888562
- Acronym / sponsor ID
- 201404024
- Conditions
- Endometrial Neoplasms
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Could not obtain an IDE on the FGFR2 assay
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Jan 2016
- Primary completion
- Jul 2018 (estimated)
- Study completion
- Jul 2023 (estimated)
- First posted
- 27 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To test the patient's cancerous tumor to see if it has a FGFR mutation and, if so, to see how their cancer responds to a treatment with the drug ponatinib as well as examine the side effects caused by ponatinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ponatinib | Experimental | Drug: PonatinibPonatinib 45mg po daily for 4 weeks (4 weeks equal 1 cycle). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- Patients must have recurrent or persistent endometrial carcinoma which is refractory to curative therapy or established treatments. Histologic confirmation of the original primary tumor is required. Patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma.
- All patients must have measurable disease. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT, and MRI, or ≥ 10 mm when measured by spiral CT.
- Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1 (Section 11.1). Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
- Patients must have a documented FGFR2 activating mutation either on primary, recurrent or metastatic biopsy. Over 90% of FGFR2 mutations occur at 7 codons. Activating mutations are defined as the known FGFR2 hotspots at S252W, P253R, S373C, Y376C, C383R, N550K, N550H, K660E.
- Patients who have received one or two prior regimen must have a GOG Performance Status of 0, 1, or 2. Patients who have received three prior regimens must have a GOG Performance Status of 0 or 1.
Key exclusion criteria (32 listed)
- Patients must not have had prior therapy with ponatinib or anti-FGFR (fibroblast growth factor receptor) therapy including brivanib, BIBF1120, and E7080.
- Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, localized cancer of the breast, and localized cancer of the head and neck, are excluded if there is any evidence of the other malignancy being present within the last five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
- Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last five years are excluded. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease.
- Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last five years are excluded. Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease.
- Patients must not be on required chronic anti-platelet therapy (aspirin >300 mg/day, or clopidogrel greater than or equal to 75mg/day).
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 |
|---|---|---|
| PonatinibAlso: Iclusig™Ponatinib 45 mg daily for 4 weeks (4 weeks equal one cycle) | Drug | Ponatinib |
Primary outcome
Tumor responses (CR + PR)
Time frame: 6 months
Ponatinib in patients with recurrent or persistent endometrioid endometrial cancer (FGFR2 activating mutation positive)for tumor responses (CR + PR) Complete Response (CR): 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): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Progression Free survival
Time frame: 6 months
Ponatinib in patients with recurrent or persistent endometrioid endometrial cancer (FGFR2 activating mutation positive) by evaluating 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.
3 secondary outcomes
Progression Free Survival
Time frame: 5.5 years
overall survival
Time frame: 5.5 years
Toxicity of Ponatinib
Time frame: 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2015.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
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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.
Matthew Powell, M.D. principal investigator
Washington University School of Medicine
Questions about this trial
What is this clinical trial studying?
A study testing Ponatinib in people with Endometrial Neoplasms, run by Washington University School of Medicine.
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 33 inclusion and 32 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: withdrawn, as of the sponsor's last update on 18 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Tumor responses (CR + PR) (time frame: 6 months). The study lists 2 primary outcomes in all. 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 18 Dec 2015.