3rd Line GISTPhase 1NCT01735968
A Dose-finding Study of a Combination of Imatinib and BYL719 in the Treatment of 3rd Line GIST Patients
A Phase 1 study testing ST571 + BYL719 in people with 3rd Line GIST, run by Novartis Pharmaceuticals at 11 sites in 8 countries.
Trial summary
The purpose of this study is to determine a maximum tolerated dose and/or recommended phase 2 dose of a combination of imatinib and BYL719 in the treatment of 3rd line GIST patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- 3rd Line GIST
- What is being tested?
- ST571 + BYL719
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 11 sitesin 8 countries
- Study dates
- 27 Feb 2013to 19 Oct 2018
- 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
- Male or female patients ≥ 18 years of age -WHO performance status (PS) of 0-2 -Histologically confirmed diagnosis of GIST that is unresectable or metastatic -.Available tissue specimen: • Dose-escalation part: patients must have available archival tumor tissue which can be shipped during the course of the study. In the absence of archival tumor tissue, patients must agree to a fresh pre-treatment biopsy at screening. • Dose-expansion part: patients must have available archival tumor tissue which can be shipped during the course of the study and must agree to a fresh pre-treatment biopsy
- Failed prior therapy with imatinib followed by sunitinib for the treatment of unresectable or metastatic GIST. Note the following specific criteria for the two parts of the trial: • Dose-escalation part: patients who failed prior therapy with imatinib and then have failed therapy with sunitinib. Treatment failure may be due to either disease progression on therapy (both imatinib and sunitinib) or intolerance to therapy (sunitinib) • Dose-escalation part patients may have had additional lines of therapy than imatinib and sunitinib dose-expansion part: patients must have documented disease progression on both imatinib and sunitinib. In addition, patients may have had no more than two lines of prior therapy (i.e. treatment with imatinib followed by treatment with sunitinib). • Note: Adjuvant imatinib will not count as a prior course of imatinib for the purposes of this criterion 6. Radiological (CT/MRI) confirmation of disease progression (RECIST criteria) during prior therapy with imatinib and sunitinib will be required for patients entering the Dose-expansion part
Who cannot join
- -Previous treatment with PI3K inhibitors -Patient has active uncontrolled or symptomatic central nervous system (CNS) metastases Note: A patient with controlled and asymptomatic CNS metastases may participate in this trial. As such, the patient must have completed any prior treatment for CNS metastases > 28 days (including radiotherapy and/or surgery) prior to start of treatment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases -Severe and/or uncontrolled concurrent medical condition that, in the opinion of the investigator, could cause unacceptable safety risks or compromise compliance with the protocol (e.g. acute or chronic liver, pancreatic disease, severe renal disease considered unrelated to study disease, chronic pulmonary disease including dyspnea at rest from any cause) -Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with FPG >120mg/dL / 6.7mmol/L, or history of documented steroid-induced diabetes mellitus -Patient who has not recovered to grade 1 or better from any adverse events related to previous imatinib and/or sunitinib therapy before screening procedures are initiated
Trial locations and contacts
11 sites in 8 countries.
11 sites in 8 countries
Germany2 sites
Novartis Investigative Site
Berlin, 13125
Novartis Investigative Site
Essen, 45147
Italy2 sites
Novartis Investigative Site
Bologna, BO, 40138
Novartis Investigative Site
Candiolo, TO, 10060
Netherlands2 sites
Novartis Investigative Site
Groningen, 9713 GZ
Novartis Investigative Site
Leiden, 2300 RC
United States1 site
Oregon Health and Science University Dept. of OHSU (3)
Portland, Oregon, 97239
About this study
Official title: A Dose-finding Phase Ib Multicenter Study of Imatinib in Combination With the Oral Phosphatidyl-inositol 3-kinase (PI3K) Inhibitor BYL719 in Patients With Gastrointestinal Stromal Tumor (GIST) Who Failed Prior Therapy With Imatinib and Sunitinib
The purpose of this study is to determine a maximum tolerated dose and/or recommended phase 2 dose of a combination of imatinib and BYL719 in the treatment of 3rd line GIST patients.
- Conditions
- 3rd Line GIST
- Being tested
- ST571 + BYL719
- Keywords
- Imatinib mesylate, STI571, BYL719, GIST, 3rd line GIST
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ST571 + BYL719Drug
Evaluable patients must meet the minimum treatment and safety evaluation requirements of the study. Patients will be treated until they experience progression of disease, withdraw consent, or experience unacceptable toxicity. One study cycle equals 28 days.
| Study group | Role | What they receive |
|---|---|---|
| STI571 (imatinib mesylate) and BYL719 | Experimental | The study will comprise of 2 parts. A dose escalation and a dose expansion part. All patients in the dose escalation part will have a pharmacokinetic (PK) run-in period of 7 days receiving imatinib monotherapy. Patients will receive increasing doses of BYL719 (200, 300, 400 mg) in combination with 400mg imatinib daily until maximum tolerated dose (MTD) and rapid phase 2 dose (RP2D) is determined. Approximately 35 patients will enter the expansion phase. Receives: Drug: ST571 + BYL719 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of dose limiting toxicities (DLTs)
Dose limiting toxicity (DLT) will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) (v4.0.3), unless otherwise specified in the protocol.
Measured: 28 days (1st cycle)
Characteristics of dose limiting toxicities (DLTs)
Dose limiting toxicity (DLT) will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) (v4.0.3), unless otherwise specified in the protocol.
Measured: 28 days (1st cycle)
Secondary outcomes (10)
Frequency and characteristics of DLTs
Dose limiting toxicity (DLT) will be assessed using CTCAE (v4.0.3), unless otherwise specified in the protocol.
Measured: 28 days (1st cycle)
Imatinib and BYL719 plasma concentrations vs time profile
Measured: 28 days (1st cycle)
Clinical benefit rate (CBR)
Clinical benefit rate is defined as the rate of confirmed complete response (CR) or partial response (PR), or stable disease (SD) which lasts for at least 16 weeks.Tumor response will be determined locally by the investigator sites according to Novartis guideline on the Response Evaluation Criteria in Solid Tumors, based on RECIST Version 1.1.
Measured: 28 days (1st cycle)
Type of adverse drug reactions
Measured: 28 days (1st cycle)
Frequency of adverse drug reactions
Measured: 28 days (1st cycle)
Severity of adverse drug reactions
Measured: 28 days (1st cycle)
Effect of basic Pharmacokinetics (PK) parameter: AUC0-24
Measured: 28 days (1st cycle)
Effect of basic PK parameter: Cmax
Measured: 28 days (1st cycle)
Effect of basic PK parameter: Tmax
Measured: 28 days (1st cycle)
Effect of basic PK parameter: CL/F
Measured: 28 days (1st cycle)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2012 (estimated)
- Study start27 Feb 2013
- Primary completion19 Oct 2018
- Study completion19 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 3rd Line GISTStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01735968
- Sponsor's protocol ID
- CSTI571X2103
- Other IDs
- 2012-003273-25
- Status last verified
- Sep 2019
- First submitted
- 15 Nov 2012
- Last updated
- 21 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pantaleo MA, Heinrich MC, Italiano A, Valverde C, Schoffski P, Grignani G, Reyners AKL, Bauer S, Reichardt P, Stark D, Berhanu G, Brandt U, Stefanelli T, Gelderblom H. A multicenter, dose-finding, phase 1b study of imatinib in combination with alpelisib as third-line treatment in patients with advanced gastrointestinal stromal tumor. BMC Cancer. 2022 May 6;22(1):511. doi: 10.1186/s12885-022-09610-4.
PubMed 35524239
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose-finding Phase Ib Multicenter Study of Imatinib in Combination With the Oral Phosphatidyl-inositol 3-kinase (PI3K) Inhibitor BYL719 in Patients With Gastrointestinal Stromal Tumor (GIST) Who Failed Prior Therapy With Imatinib and Sunitinib
- ClinicalTrials.gov ID
- NCT01735968
- Acronym / sponsor ID
- CSTI571X2103
- Conditions
- 3rd Line GIST
- Keywords
- Imatinib mesylate, STI571, BYL719, GIST, 3rd line GIST
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 27 Feb 2013 (actual)
- Primary completion
- 19 Oct 2018 (actual)
- Study completion
- 19 Oct 2018 (actual)
- First posted
- 28 Nov 2012 (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.
The purpose of this study is to determine a maximum tolerated dose and/or recommended phase 2 dose of a combination of imatinib and BYL719 in the treatment of 3rd line GIST patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| STI571 (imatinib mesylate) and BYL719 | Experimental | Drug: ST571 + BYL719The study will comprise of 2 parts. A dose escalation and a dose expansion part. All patients in the dose escalation part will have a pharmacokinetic (PK) run-in period of 7 days receiving imatinib monotherapy. Patients will receive increasing doses of BYL719 (200, 300, 400 mg) in combination with 400mg imatinib daily until maximum tolerated dose (MTD) and rapid phase 2 dose (RP2D) is determined. Approximately 35 patients will enter the expansion phase. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Male or female patients ≥ 18 years of age -WHO performance status (PS) of 0-2 -Histologically confirmed diagnosis of GIST that is unresectable or metastatic -.Available tissue specimen: • Dose-escalation part: patients must have available archival tumor tissue which can be shipped during the course of the study. In the absence of archival tumor tissue, patients must agree to a fresh pre-treatment biopsy at screening. • Dose-expansion part: patients must have available archival tumor tissue which can be shipped during the course of the study and must agree to a fresh pre-treatment biopsy
- Failed prior therapy with imatinib followed by sunitinib for the treatment of unresectable or metastatic GIST. Note the following specific criteria for the two parts of the trial: • Dose-escalation part: patients who failed prior therapy with imatinib and then have failed therapy with sunitinib. Treatment failure may be due to either disease progression on therapy (both imatinib and sunitinib) or intolerance to therapy (sunitinib) • Dose-escalation part patients may have had additional lines of therapy than imatinib and sunitinib dose-expansion part: patients must have documented disease progression on both imatinib and sunitinib. In addition, patients may have had no more than two lines of prior therapy (i.e. treatment with imatinib followed by treatment with sunitinib). • Note: Adjuvant imatinib will not count as a prior course of imatinib for the purposes of this criterion 6. Radiological (CT/MRI) confirmation of disease progression (RECIST criteria) during prior therapy with imatinib and sunitinib will be required for patients entering the Dose-expansion part
Key exclusion criteria (1 listed)
- -Previous treatment with PI3K inhibitors -Patient has active uncontrolled or symptomatic central nervous system (CNS) metastases Note: A patient with controlled and asymptomatic CNS metastases may participate in this trial. As such, the patient must have completed any prior treatment for CNS metastases > 28 days (including radiotherapy and/or surgery) prior to start of treatment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases -Severe and/or uncontrolled concurrent medical condition that, in the opinion of the investigator, could cause unacceptable safety risks or compromise compliance with the protocol (e.g. acute or chronic liver, pancreatic disease, severe renal disease considered unrelated to study disease, chronic pulmonary disease including dyspnea at rest from any cause) -Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with FPG >120mg/dL / 6.7mmol/L, or history of documented steroid-induced diabetes mellitus -Patient who has not recovered to grade 1 or better from any adverse events related to previous imatinib and/or sunitinib therapy before screening procedures are initiated
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 |
|---|---|---|
| ST571 + BYL719Evaluable patients must meet the minimum treatment and safety evaluation requirements of the study. Patients will be treated until they experience progression of disease, withdraw consent, or experience unacceptable toxicity. One study cycle equals 28 days. | Drug | STI571 (imatinib mesylate) and BYL719 |
Primary outcome
Frequency of dose limiting toxicities (DLTs)
Time frame: 28 days (1st cycle)
Dose limiting toxicity (DLT) will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) (v4.0.3), unless otherwise specified in the protocol.
Characteristics of dose limiting toxicities (DLTs)
Time frame: 28 days (1st cycle)
Dose limiting toxicity (DLT) will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) (v4.0.3), unless otherwise specified in the protocol.
10 secondary outcomes
Frequency and characteristics of DLTs
Time frame: 28 days (1st cycle)
Imatinib and BYL719 plasma concentrations vs time profile
Time frame: 28 days (1st cycle)
Clinical benefit rate (CBR)
Time frame: 28 days (1st cycle)
Type of adverse drug reactions
Time frame: 28 days (1st cycle)
Frequency of adverse drug reactions
Time frame: 28 days (1st cycle)
Severity of adverse drug reactions
Time frame: 28 days (1st cycle)
Effect of basic Pharmacokinetics (PK) parameter: AUC0-24
Time frame: 28 days (1st cycle)
Effect of basic PK parameter: Cmax
Time frame: 28 days (1st cycle)
Effect of basic PK parameter: Tmax
Time frame: 28 days (1st cycle)
Effect of basic PK parameter: CL/F
Time frame: 28 days (1st cycle)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2020.
- Derived from this study: PubMed 35524239Pantaleo MA, Heinrich MC, Italiano A, Valverde C, Schoffski P, Grignani G, Reyners AKL, Bauer S, Reichardt P, Stark D, Berhanu G, Brandt U, Stefanelli T, Gelderblom H. A multicenter, dose-finding, phase 1b study of imatinib in combination with alpelisib as third-line treatment in patients with advanced gastrointestinal stromal tumor. BMC Cancer. 2022 May 6;22(1):511. doi: 10.1186/s12885-022-09610-4.
- Results for CSTI571X2103 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
11 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ST571 + BYL719 in people with 3rd Line GIST, run by Novartis Pharmaceuticals at 11 sites in 8 countries.
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 2 inclusion and 1 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 21 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Germany, Italy, Netherlands, United States, Belgium and 3 more countries. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Frequency of dose limiting toxicities (DLTs) (time frame: 28 days (1st cycle)). 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?
On the ClinicalTrials.gov record for NCT01735968, which also lists 1 linked publication.
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 21 Dec 2020.