GISTPhase 2NCT01089595
Trial of Tasigna (Nilotinib) 400 mg Twice Daily Alone or With Gleevec (Imatinib Mesylate) 400 mg Daily for Patients With Advanced Gastrointestinal Stromal Tumor (GIST)
A Phase 2 study testing Nilotinib and Nilotinib with Imatinib in people with GIST and Metastatic Disease, run by Fox Chase Cancer Center at 3 sites in United States.
Trial summary
Patients with advanced GIST are treated with imatinib. This study seeks to look at a new therapeutic agent at the time of tumor progression following treatment with 600-800 mg daily of imatinib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GIST, Metastatic Disease
- What is being tested?
- Nilotinib and Nilotinib with Imatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2009to Mar 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- histologically or cytologically confirmed GIST.
- advanced/metastatic GIST.
- experienced failure of prior treatment with imatinib 600-800 mg per day defined by progression of disease according to RECIST criteria during treatment. Radiographic evidence of PD on imatinib must be confirmed by the Investigator prior to enrollment.
- May have focal progression of disease including a new enhancing nodular focus within a pre-existing tumor nodule; such a nodule should be considered measurable by standard RECIST criteria.
- measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
- At least 4 weeks since prior therapy with imatinib \& resolution of all acute toxic effects of the prior therapy or surgical procedure to grade ≤1.
Show all 20Show fewer
- Age >18 years.
- ECOG performance status 0-2.
- Normal organ and marrow function as defined below:
- ANC >1,500/mcL
- Platelets >100,000/mcL
- Total bilirubin < or equal to 1.5 X ULN
- AST(SGOT)/ALT(SGPT) < or equal to 2.5 X ULN OR < or equal to 5.0 X ULN if considered due to tumor
- Amylase/Lipase < or equal to 1.5 X ULN
- Alkaline Phosphatase < or equal to 2.5 X ULN or </= 5 X ULN if considered tumor related.
- Potassium, magnesium, calcium, phosphorus, creatinine WNL prior to randomization
- OR
- Creatinine clearance of > 50 calculated by cockroft-gault formula
- WOCBP must have negative pregnancy test within 7 days of first treatment and use appropriate contraception.
- Ability to understand and willingness to sign a written informed consent document.
Who cannot join
- Have received nilotinib or additional tyrosine kinase inhibitors or additional targeted therapies (except for imatinib).
- May not be receiving any other investigational agents within 4 weeks before treatment.
- Prior or concomitant malignancies (with a relapse in the last 5 years or requiring active treatment) other than GIST and with exception of previous or concomitant basal cell skin, previous cervical carcinoma in situ.
- Impaired cardiac function, including any one of the following:
- Complete left bundle branch block. Ventricular paced cardiac pacemaker. Congenital long QT syndrome or family history of long QT syndrome. History of or presence of symptomatic ventricular or atrial tachyarrhythmias. Clinically significant resting bradycardia (< 50 beats per minute). QTc > 480 msec on screening ECG (using the QTcF formula). If QTc > 480 msec and electrolytes are not within normal ranges (electrolytes should be corrected and then the patient rescreened for QTc).
- Right bundle branch block plus left anterior hemiblock, bifascicular block. Myocardial infarction within 12 months prior to Visit 1. Other clinically significant heart diseases (e.g., unstable angina, congestive heart failure or uncontrolled hypertension).
Show all 13Show fewer
- Severe and/or uncontrolled concurrent medical disease that could cause unacceptable safety risks or compromise compliance with protocol e.g. impairment of GI function, or GI disease that may significantly alter absorption of study drugs; uncontrolled diabetes; active infections; psychiatric illness/social situation that would limit compliance with study requirements.
- Inability to remain laying down in PET scanner for up to one hour.
- Use of any medications that prolong the QT interval and CYP3A4 inhibitors if treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug administration.
- Major surgery ≤ 2 weeks prior to Visit 1 or who have not recovered from side effects of such surgery.
- Known history of noncompliance to medical regimens or inability/unwillingness to return for scheduled visits, patients who are pregnant or breast feeding, patients unwilling or unable to comply with the requirements for the protocol.
- Known chronic liver disease (i.e., chronic active, hepatitis, and cirrhosis).
- Known diagnosis of HIV, currently taking combination antiretroviral therapy.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Siteman Cancer Center, Washington University School of Mediciine
St Louis, Missouri, 63110
Wake Forest University
Winston-Salem, North Carolina, 27157-1082
About this study
Official title: Open Label Phase II Randomized Trial of Tasigna (Nilotinib) 400 mg Twice Daily Alone or in Combination With Gleevec (Imatinib Mesylate) 400 mg Daily for Patients With Advanced GIST That Have Progressed on High Dose Imatinib
Patients with advanced GIST are treated with imatinib. This study seeks to look at a new therapeutic agent at the time of tumor progression following treatment with 600-800 mg daily of imatinib. The study is looking to see if Nilotinib (tasigna) alone or in combination with imatinib (gleevec) is more effective at controlling disease.
Read the detailed description
Resistance to imatinib does develop and represents a major clinical challenge. Mechanisms implicated in imatinib resistance include: target resistance due to new KIT or PDGFRA mutations or over expression of the KIT protein; target modulation due to activation of an alternate receptor tyrosine kinase protein with loss of KIT oncoprotein expression; functional resistance due to KIT or PDGFRA activation without a secondary mutation; and alterations in imatinib uptake by P-glycoprotein.
This study seeks to test nilotinib alone and nilotinib in combination with imatinib in patients that have progressed on imatinib.
Nilotinib is a new synthetic second-generation inhibitor of the BCR-ABL tyrosine kinase that competes for the ATP-bindings sites of BCR-ABL. A completed phase I trial assessed the activity of nilotinib alone and in combination with imatinib in patients that have progressed on imatinib in a population of patients with imatinib refractory and intolerant patients. There were rare responses, but stable disease was observed in grater than 50% of patients.
This study is aiming to treat patients with advanced or metastatic GIST who have disease progression on imatinib dose escalated up to 600 mg or greater. The rationale for exploring Nilotinib in this setting is to determine if it has therapeutic efficacy, with potentially less toxicity than the current standard of care for second line therapy. In addition, since it is not uncommon to see progression of some metastatic GIST lesions on imatinib, while others remain controlled, adding nilotinib may treat the progressing lesions while imatinib continues to control the areas without disease progression.
- Conditions
- GIST, Metastatic Disease
- Being tested
- Nilotinib, Nilotinib with Imatinib
- Keywords
- Imatinib Resistance, GIST, Advanced Disease, Nilotinib
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NilotinibDrug
Also called Tasigna
Nilotinib 400 mg po bid
Nilotinib with ImatinibDrug
Also called Tasigna, Gleevec
Nilotinib 400 mg po BID Imatinib 400 mg po daily
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib | Active comparator | Nilotinib 400 mg po bid Receives: Drug: Nilotinib |
| Nilotinib + Imatinib | Active comparator | Nilotinib 400 mg BID with Imatinib 400 mg daily Receives: Drug: Nilotinib with Imatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression. It will be determined for both RECIST (Response Evaluation Criteria in Solid Tumors) and CHOI criteria.
Measured: 6 months until death or for 5 years
Secondary outcomes (1)
Best Overall Response Using Response Evaluation Criteria in Solid Tumors, Choi Criteria, and Positron Emission Tomography Imaging
Measured: Every 8 weeks for up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2010 (estimated)
- Study startFeb 2009
- Primary completionNov 2011
- Study completionMar 2012
Why it stopped: Novartis is ending their research program for Nilotinib in GIST.
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 GISTStudies of the same condition, open and under way.
- More trials run by Fox Chase Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Margaret von Mehren, MD, Principal investigator, Fox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01089595
- Sponsor's protocol ID
- FER-SAR-023
- Status last verified
- Jan 2017
- First submitted
- 28 Jan 2010
- Last updated
- 15 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Phase II Randomized Trial of Tasigna (Nilotinib) 400 mg Twice Daily Alone or in Combination With Gleevec (Imatinib Mesylate) 400 mg Daily for Patients With Advanced GIST That Have Progressed on High Dose Imatinib
- ClinicalTrials.gov ID
- NCT01089595
- Acronym / sponsor ID
- FER-SAR-023
- Conditions
- GIST, Metastatic Disease
- Keywords
- Imatinib Resistance, GIST, Advanced Disease, Nilotinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Novartis is ending their research program for Nilotinib in GIST.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Feb 2009
- Primary completion
- Nov 2011 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 18 Mar 2010 (estimated)
- Results
- Posted 15 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with advanced GIST are treated with imatinib. This study seeks to look at a new therapeutic agent at the time of tumor progression following treatment with 600-800 mg daily of imatinib. The study is looking to see if Nilotinib (tasigna) alone or in combination with imatinib (gleevec) is more effective at controlling disease.
Detailed description
Resistance to imatinib does develop and represents a major clinical challenge. Mechanisms implicated in imatinib resistance include: target resistance due to new KIT or PDGFRA mutations or over expression of the KIT protein; target modulation due to activation of an alternate receptor tyrosine kinase protein with loss of KIT oncoprotein expression; functional resistance due to KIT or PDGFRA activation without a secondary mutation; and alterations in imatinib uptake by P-glycoprotein.
This study seeks to test nilotinib alone and nilotinib in combination with imatinib in patients that have progressed on imatinib.
Nilotinib is a new synthetic second-generation inhibitor of the BCR-ABL tyrosine kinase that competes for the ATP-bindings sites of BCR-ABL. A completed phase I trial assessed the activity of nilotinib alone and in combination with imatinib in patients that have progressed on imatinib in a population of patients with imatinib refractory and intolerant patients. There were rare responses, but stable disease was observed in grater than 50% of patients.
This study is aiming to treat patients with advanced or metastatic GIST who have disease progression on imatinib dose escalated up to 600 mg or greater. The rationale for exploring Nilotinib in this setting is to determine if it has therapeutic efficacy, with potentially less toxicity than the current standard of care for second line therapy. In addition, since it is not uncommon to see progression of some metastatic GIST lesions on imatinib, while others remain controlled, adding nilotinib may treat the progressing lesions while imatinib continues to control the areas without disease progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nilotinib | Active comparator | Drug: NilotinibNilotinib 400 mg po bid |
| Nilotinib + Imatinib | Active comparator | Drug: Nilotinib with ImatinibNilotinib 400 mg BID with Imatinib 400 mg daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- histologically or cytologically confirmed GIST.
- advanced/metastatic GIST.
- experienced failure of prior treatment with imatinib 600-800 mg per day defined by progression of disease according to RECIST criteria during treatment. Radiographic evidence of PD on imatinib must be confirmed by the Investigator prior to enrollment.
- May have focal progression of disease including a new enhancing nodular focus within a pre-existing tumor nodule; such a nodule should be considered measurable by standard RECIST criteria.
- measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
Key exclusion criteria (13 listed)
- Have received nilotinib or additional tyrosine kinase inhibitors or additional targeted therapies (except for imatinib).
- May not be receiving any other investigational agents within 4 weeks before treatment.
- Prior or concomitant malignancies (with a relapse in the last 5 years or requiring active treatment) other than GIST and with exception of previous or concomitant basal cell skin, previous cervical carcinoma in situ.
- Impaired cardiac function, including any one of the following:
- Complete left bundle branch block. Ventricular paced cardiac pacemaker. Congenital long QT syndrome or family history of long QT syndrome. History of or presence of symptomatic ventricular or atrial tachyarrhythmias. Clinically significant resting bradycardia (< 50 beats per minute). QTc > 480 msec on screening ECG (using the QTcF formula). If QTc > 480 msec and electrolytes are not within normal ranges (electrolytes should be corrected and then the patient rescreened for QTc).
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 |
|---|---|---|
| NilotinibAlso: TasignaNilotinib 400 mg po bid | Drug | Nilotinib |
| Nilotinib with ImatinibAlso: Tasigna, GleevecNilotinib 400 mg po BID Imatinib 400 mg po daily | Drug | Nilotinib + Imatinib |
Primary outcome
Progression Free Survival
Time frame: 6 months until death or for 5 years
Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression. It will be determined for both RECIST (Response Evaluation Criteria in Solid Tumors) and CHOI criteria.
1 secondary outcome
Best Overall Response Using Response Evaluation Criteria in Solid Tumors, Choi Criteria, and Positron Emission Tomography Imaging
Time frame: Every 8 weeks for up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for GIST
RecruitingPhase 2
A Study to Learn More About How Well Treatment With Sevabertinib (BAY 2927088) Tablets Works and How Safe it is in Participants Who Have a Solid Tumor With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)
Advanced Solid Tumors, HER2 Mutation
RecruitingPhase 2
Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015)
Pheochromocytoma/Paraganglioma, Pancreatic Neuroendocrine Tumor
RecruitingObservational study
Surgery in Gastrointestinal Stromal Tumors (GISTs) for Treatment, Tumor Modeling, and Genomic Analysis
Gastric Cancer, Gastric Neoplasm
RecruitingPhase 1
A Study of Ziftomenib in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)
Gastrointestinal Stromal Tumor (GIST), Gastrointestinal Stromal Cancer
RecruitingPhase 1
Phase I Trial to Determine the Dose and Evaluate the PK and Safety of Lutetium Lu 177 Edotreotide Therapy in Pediatric Participants With SSTR-positive Tumors
Somatostatin Receptor Positive, NETs
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.
Margaret von Mehren, MD principal investigator
Fox Chase Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nilotinib and Nilotinib with Imatinib in people with GIST and Metastatic Disease, run by Fox Chase Cancer Center 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 20 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Mar 2017. 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 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 15 Mar 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?
Progression Free Survival (time frame: 6 months until death or for 5 years). 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 15 Mar 2017.