ChordomaPhase 1NCT01175109
Study of Imatinib, a Platelet-derived Growth Factor Receptor Inhibitor, and LBH589, a Histone Deacetylase Inhibitor, in the Treatment of Newly Diagnosed and Recurrent Chordoma
A Phase 1 study testing Imatinib + LBH589 in people with Chordoma, run by Deric M Park MD at 3 sites in United States.
Trial summary
This is a multi-center study to assess the safety and to determine the maximum tolerated dose of the combination of imatinib and LBH589 in patients with newly diagnosed and recurrent chordoma. For the recurrent population, those patients that do not require immediate surgical resection will be eligible. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chordoma
- What is being tested?
- Imatinib + LBH589
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 3 sitesUnited States
- Study dates
- Oct 2011to Dec 2013
- Phase
- Phase 1
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients greater than or equal to 18 years of age.
- Histologically documented diagnosis of chordoma
- At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors, see Appendix 3).
- Performance status 0,1, or 2 (ECOG) (see Section 6)
- Patients must have adequate bone marrow and end organ function, as defined as the following:
- WBC > 3.0 x 109/L
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- ANC > 1.5 x 109/L,
- Platelets > 100 x 109/L
- Hemoglobin > 10 gm/dl
- Total bilirubin < 1.5 x ULN (Does not apply to patients with isolated hyperbilirubinemia (e.g., Gilbert's disease) grade <3.
- AST/SGOT and ALT/SGPT < 2.5 x UNL
- Serum creatinine ≤ 2.5 x ULN or 24 hr creatinine clearance ≥ 50ml/min
- Serum albumin ≤ 3g/dL
- Serum amylase and lipase ≤ 1.5 x ULN
- Alkaline phosphatase ≤ 2.5 x ULN
- Patients must have the following laboratory values (WNL = within normal limits at the local institution lab) or corrected to within normal limits with supplements prior to the first dose of study medication:
- Potassium (WNL)
- Magnesium (WNL)
- Phosphorus (WNL)
- Calcium (WNL)
- Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
- A scan should be performed within 14 days prior to registration. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement.
- Patients must have an interval of greater than or equal to 3 months from the completion of radiation therapy to study entry.
- Patients must be willing to participate in the pharmacokinetic studies.
- Written, voluntary informed consent.
Who cannot join
- Patient has received any other investigational agents within 28 days of first day of study drug dosing for treatment of chordoma, unless the disease is rapidly progressing. Patients who have been previously treated with imatinib or LBH589 are ineligible.
- Patients must not be on enzyme inducing anticonvulsants or valproic acid, a seizure medication with HDAC inhibition activity.
- Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
- Patient 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)
- Impaired cardiac function including any one of the following:
- Inability to monitor the QT/QTc interval on ECG
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- Long QT syndrome or a known family history of long QT syndrome.
- Clinically significant resting brachycardia (<50 beats per minute)
- QTc > 450 msec on baseline ECG (using the QTcF formula). If QTcF >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
- Myocardial infarction within 12 months prior to starting study
- Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension)
- History of or presence of clinically significant ventricular or atrial tachyarrhythmias
- Female patients who are pregnant or breast-feeding.
- Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
- Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
- Patient has known brain metastasis
- Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
- Patient received chemotherapy within 4 weeks (6 weeks for nitrosourea or mitomycin-C)prior to study entry, unless the disease is rapidly progressing.
- Patient receiving concurrent treatment with warfarin.
- Patient previously received radiotherapy to > 25 % of the bone marrow
- Patient had a major surgery within 2 weeks prior to study entry.
- Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
- Patients may not be receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to imatinib or LBH589 used in study.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Michigan
Ann Arbor, Michigan, 48109
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Virginia
Charlottesville, Virginia, 22908
About this study
Official title: Multicenter Phase I Study of Imatinib, a Platelet-derived Growth Factor Receptor Inhibitor, and LBH589, a Histone Deacetylase Inhibitor, in the Treatment of Newly Diagnosed and Recurrent Chordoma
This is a multi-center study to assess the safety and to determine the maximum tolerated dose of the combination of imatinib and LBH589 in patients with newly diagnosed and recurrent chordoma. For the recurrent population, those patients that do not require immediate surgical resection will be eligible. Patients will be treated with 4 cycles, followed by surgical resection if possible. If indicated, surgery may take place prior to the completion of 4 cycles.
- Conditions
- Chordoma
- Being tested
- Imatinib + LBH589
- Keywords
- Chordoma
- Medical subject headings
- Chordoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib + LBH589Drug
Escalating doses of imatinib and LBH589 will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Escalating doses of imatinib and LBH589 | Experimental | Study will incorporate a "3+3" dose escalation design. Receives: Drug: Imatinib + LBH589 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of dose limiting toxicities
Measured: At time of study drug discontinuation
Secondary outcomes (2)
Tumor response
Tumor response will be evaluated using the RECIST criteria
Measured: Week 7
Tumor response
Tumor response will be evaluated using the RECIST criteria.
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2010 (estimated)
- Study startOct 2011
- Primary completionDec 2013 (estimated)
- Study completionDec 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ChordomaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Deric M Park MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Deric M Park MD, University of Virginia
- Investigators
- Deric M Park, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01175109
- Sponsor's protocol ID
- 15120
- Status last verified
- Dec 2012
- First submitted
- 28 Jul 2010
- Last updated
- 27 Dec 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Phase I Study of Imatinib, a Platelet-derived Growth Factor Receptor Inhibitor, and LBH589, a Histone Deacetylase Inhibitor, in the Treatment of Newly Diagnosed and Recurrent Chordoma
- ClinicalTrials.gov ID
- NCT01175109
- Acronym / sponsor ID
- 15120
- Conditions
- Chordoma
- Keywords
- Chordoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Deric M Park MDUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2013 (estimated)
- First posted
- 4 Aug 2010 (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.
This is a multi-center study to assess the safety and to determine the maximum tolerated dose of the combination of imatinib and LBH589 in patients with newly diagnosed and recurrent chordoma. For the recurrent population, those patients that do not require immediate surgical resection will be eligible. Patients will be treated with 4 cycles, followed by surgical resection if possible. If indicated, surgery may take place prior to the completion of 4 cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Escalating doses of imatinib and LBH589 | Experimental | Drug: Imatinib + LBH589Study will incorporate a "3+3" dose escalation design. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Patients greater than or equal to 18 years of age.
- Histologically documented diagnosis of chordoma
- At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors, see Appendix 3).
- Performance status 0,1, or 2 (ECOG) (see Section 6)
- Patients must have adequate bone marrow and end organ function, as defined as the following:
Key exclusion criteria (24 listed)
- Patient has received any other investigational agents within 28 days of first day of study drug dosing for treatment of chordoma, unless the disease is rapidly progressing. Patients who have been previously treated with imatinib or LBH589 are ineligible.
- Patients must not be on enzyme inducing anticonvulsants or valproic acid, a seizure medication with HDAC inhibition activity.
- Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
- Patient 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)
- Impaired cardiac function including any one of the following:
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 |
|---|---|---|
| Imatinib + LBH589Escalating doses of imatinib and LBH589 will be administered. | Drug | Escalating doses of imatinib and LBH589 |
Primary outcome
Number of dose limiting toxicities
Time frame: At time of study drug discontinuation
2 secondary outcomes
Tumor response
Time frame: Week 7
Tumor response
Time frame: Week 12
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2012.
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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.
Deric M Park, MD principal investigator
University of Virginia
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Imatinib + LBH589 in people with Chordoma, run by Deric M Park MD 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 25 inclusion and 24 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: status not confirmed, as of the sponsor's last update on 27 Dec 2012. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Number of dose limiting toxicities (time frame: At time of study drug discontinuation). 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 27 Dec 2012.