NeurofibromatosisEarly Phase 1NCT01275586
Study of Tasigna®/Nilotinib (AMN107) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas
A Early Phase 1 study testing Tasigna in people with Neurofibromatosis and NF1, run by Indiana University at 1 site in United States.
Trial summary
The purpose of this Pilot Study is to determine if NF1 patients with plexiform neurofibromas treated with Tasgina® respond to therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurofibromatosis, NF1, Neurofibromas
- What is being tested?
- Tasigna
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2011to Oct 2016
- Phase
- Early Phase 1
- 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 > or = 18 years of age.
- Clinical diagnosis of neurofibromatosis type 1 (NF1)
- Presence of clinically significant plexiform neurofibromas (tumors that are potentially life threatening or are impinging on vital structures or significant impairment in the quality of life from pain or other symptoms)
- Patients must have measurable disease by magnetic resonance imaging (MRI)(as defined by Response Evaluation Criteria in Solid Tumors, see Appendix 4)
- Patients must have a Karnofsky Performance Status of ≥50%
- Adequate end organ function, defined as the following:
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- Creatinine < 1.5 x ULN
- ANC > 1.5 x 109/L
- Platelets > 100 x 109/L
- 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 ULN
- 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)
Who cannot join
- Previous treatment with any other tyrosine kinase inhibitor
- Impaired cardiac function including any one of the following:
- Inability to monitor the QT interval on ECG ii. Congenital long QT syndrome or a known family history of long QT syndrome. iii. Clinically significant resting brachycardia (<50 beats per minute) iv. QTc > 450 msec on baseline ECG. If QTc >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc v. Myocardial infarction within 12 months prior to starting study vi. Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension) vii. History or presence of clinically significant ventricular or atrial tachyarrhythmias
- Patients currently receiving treatment with strong CYP3A4 inhibitors and treatment cannot be either discontinued or switched to a different medication prior to starting study drug. (Appendix 1).
- Patients currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug (Appendix 3)
- Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery).
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- Acute or chronic pancreatic disease
- Patient has known brain metastasis. Non specific CNS changes on MRI characteristic with NF1 are allowed.
- Another primary malignant disease, which requires systemic treatment (chemotherapy or radiation)
- Acute or chronic liver disease or severe renal disease considered unrelated to the cancer.
- History of significant congenital or acquired bleeding disorder unrelated to cancer
- Major surgery within 4 weeks prior to Day 1 of the study or who have not recovered from prior surgery.
- Treatment with other investigational agents within 30 days of Day 1.
- History of non-compliance to medical regimens or inability to grant consent.
- Female patients who are pregnant, breast feeding, or of childbearing potential without a negative pregnancy test prior to baseline. Male or female patients of childbearing potential unwilling to use contraceptive precautions throughout the trial and 3 months following discontinuation of study drug. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Women of childbearing potential must have a negative serum pregnancy test prior to the first dose of nilotinib.
Trial locations and contacts
1 site in 1 country.
United States1 site
Riley Hospital for Children
Indianapolis, Indiana, 46202
About this study
Official title: Pilot Study of Tasigna®/Nilotinib (AMN107) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas
The purpose of this Pilot Study is to determine if NF1 patients with plexiform neurofibromas treated with Tasgina® respond to therapy.
Read the detailed description
This is an open-label Pilot Study to determine the efficacy of Tasigna® in adults with neurofibromatosis (NF1) and plexiform neurofibromas with the secondary goals of determining the toxicity, and tumor markers in this genetically defined population. The rationale for this study arises from the response of human and murine NF1 cells to Tasigna® in vitro and the clinical response in NF1 patients with plexiform neurofibromas using the similar drug, Gleevec®. Following enrollment each subject will initially receive Tasigna orally at 200 mg twice daily for two weeks. If tolerated, the dose will be increased to 300 mg twice daily after a minimum of two weeks and will be increase to a maximum dose of 400mg twice daily after an additional two weeks if tolerated. Subjects will have his/her dose increased as tolerated dose during the first three months of therapy. The maximum targeted dose is 400mg twice daily.
- Conditions
- Neurofibromatosis, NF1, Neurofibromas
- Being tested
- Tasigna
- Keywords
- NF1, plexiform neurofibromas, nilotinib, Tasigna
- Medical subject headings
- Neurofibromatoses, Neurofibroma, Neurofibroma, Plexiform
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TasignaDrug
Also called Nilotinib
Following enrollment each subject will initially receive Tasigna orally at 200 mg twice daily for two weeks. If tolerated, the dose will be increased to 300 mg twice daily after a minimum of two weeks and will be increase to a maximum dose of 400mg twice daily after an additional two weeks if tolerated.
| Study group | Role | What they receive |
|---|---|---|
| Tasigna | Experimental | Following enrollment each subject will initially receive the drug Tasigna orally at 200 mg twice daily for two weeks. If tolerated, the dose will be increased to 300 mg twice daily after a minimum of two weeks and will be increase to a maximum dose of 400mg twice daily after an additional two weeks if tolerated. Subjects will have his/her dose increased as tolerated dose during the first three months of therapy. The maximum targeted dose is 400mg twice daily. Receives: Drug: Tasigna |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Response
To estimate the disease control rate (PD,SD, PR, CR) with Tasigna® in patients with neurofibromas (NF1) using standard RECIST criteria. Complete Response (CR) is defined as; disappearance of all target lesions. Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as a reference the baseline sum longest diameter. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started. Disease Progression (PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
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 posted12 Jan 2011 (estimated)
- Study startJan 2011
- Primary completionJul 2016
- Study completionOct 2016
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 NeurofibromatosisStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Melissa Markel, MD, Study chair, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01275586
- Sponsor's protocol ID
- 1008-06
- Other IDs
- CAMN107YUS29T
- Status last verified
- Apr 2017
- First submitted
- 11 Jan 2011
- Last updated
- 12 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Tasigna®/Nilotinib (AMN107) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas
- ClinicalTrials.gov ID
- NCT01275586
- Acronym / sponsor ID
- 1008-06
- Conditions
- Neurofibromatosis, NF1, Neurofibromas
- Keywords
- NF1, plexiform neurofibromas, nilotinib, Tasigna
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jan 2011
- Primary completion
- Jul 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 12 Jan 2011 (estimated)
- Results
- Posted 12 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this Pilot Study is to determine if NF1 patients with plexiform neurofibromas treated with Tasgina® respond to therapy.
Detailed description
This is an open-label Pilot Study to determine the efficacy of Tasigna® in adults with neurofibromatosis (NF1) and plexiform neurofibromas with the secondary goals of determining the toxicity, and tumor markers in this genetically defined population. The rationale for this study arises from the response of human and murine NF1 cells to Tasigna® in vitro and the clinical response in NF1 patients with plexiform neurofibromas using the similar drug, Gleevec®. Following enrollment each subject will initially receive Tasigna orally at 200 mg twice daily for two weeks. If tolerated, the dose will be increased to 300 mg twice daily after a minimum of two weeks and will be increase to a maximum dose of 400mg twice daily after an additional two weeks if tolerated. Subjects will have his/her dose increased as tolerated dose during the first three months of therapy. The maximum targeted dose is 400mg twice daily.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tasigna | Experimental | Drug: TasignaFollowing enrollment each subject will initially receive the drug Tasigna orally at 200 mg twice daily for two weeks. If tolerated, the dose will be increased to 300 mg twice daily after a minimum of two weeks and will be increase to a maximum dose of 400mg twice daily after an additional two weeks if tolerated. Subjects will have his/her dose increased as tolerated dose during the first three months of therapy. The maximum targeted dose is 400mg twice daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients > or = 18 years of age.
- Clinical diagnosis of neurofibromatosis type 1 (NF1)
- Presence of clinically significant plexiform neurofibromas (tumors that are potentially life threatening or are impinging on vital structures or significant impairment in the quality of life from pain or other symptoms)
- Patients must have measurable disease by magnetic resonance imaging (MRI)(as defined by Response Evaluation Criteria in Solid Tumors, see Appendix 4)
- Patients must have a Karnofsky Performance Status of ≥50%
Key exclusion criteria (15 listed)
- Previous treatment with any other tyrosine kinase inhibitor
- Impaired cardiac function including any one of the following:
- Patients currently receiving treatment with strong CYP3A4 inhibitors and treatment cannot be either discontinued or switched to a different medication prior to starting study drug. (Appendix 1).
- Patients currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug (Appendix 3)
- Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery).
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 |
|---|---|---|
| TasignaAlso: NilotinibFollowing enrollment each subject will initially receive Tasigna orally at 200 mg twice daily for two weeks. If tolerated, the dose will be increased to 300 mg twice daily after a minimum of two weeks and will be increase to a maximum dose of 400mg twice daily after an additional two weeks if tolerated. | Drug | Tasigna |
Primary outcome
Disease Response
Time frame: 6 months
To estimate the disease control rate (PD,SD, PR, CR) with Tasigna® in patients with neurofibromas (NF1) using standard RECIST criteria. Complete Response (CR) is defined as; disappearance of all target lesions. Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as a reference the baseline sum longest diameter. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started. Disease Progression (PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Melissa Markel, MD study chair
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Tasigna in people with Neurofibromatosis and NF1, run by Indiana University 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 19 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Apr 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 12 Apr 2017). 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?
Disease Response (time frame: 6 months). 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 12 Apr 2017.