Gastrointestinal Stromal Tumor (GIST)Phase 2NCT01294202
A Study to Investigate the Safety and Efficacy of AT13387, Alone or in Combination With Imatinib, in Patients With GIST
A Phase 2 study testing AT13387 and Imatinib in people with Gastrointestinal Stromal Tumor (GIST), run by Astex Pharmaceuticals, Inc. at 8 sites in United States.
Trial summary
The purpose of this study is to investigate if an investigational drug called AT13387 is active against Gastrointestinal Stromal Tumor (GIST) that is resistant to other treatments, and to understand more about the safety of AT13387. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumor (GIST)
- What is being tested?
- AT13387 and Imatinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 8 sitesUnited States
- Study dates
- Mar 2011to Jul 2014
- Phase
- Phase 2
- 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
- Ability to understand the risks of the study and to provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations).
- Age 18 years or older.
- Unresectable and/or metastatic malignant GIST with objective progression of disease following treatment with a maximum of 3 tyrosine kinase inhibitors (TKIs) including imatinib. To clarify, it is the number of TKIs - up to a maximum of three agents, including imatinib - that is the criterion for entry, not the number of prior courses of TKI treatment.
- Measurable disease.
- ECOG performance status 0 or 1.
- Negative blood or urine pregnancy test (within 7 days prior to commencing treatment), or documented evidence of surgical sterility, or natural or treatment-induced post-menopausal status with last menses >1 year ago.
- Willing to provide a tissue block or unstained slides of archived tumour for central pathology review and genotyping, or a full pathology report and results of genotyping of a previous tumour sample, or willing to undergo a new tumour biopsy for central pathology review and genotyping during the screening period of the study (prior to dosing)
Who cannot join
- Pregnancy or lactation (women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to commencing treatment ). Male and female patients of childbearing potential must use appropriate birth control (abstinence, barrier methods, oral contraceptives and/or intrauterine devices) during the entire duration of the study, or the patient must be surgically sterile (with documentation in the patient's medical records).
- Impaired liver function, as evidenced by prior liver segmentectomy or hemi-hepatectomy; or alanine or aspartate aminotransferase (ALAT/ASAT) >2.5x ULN; or alkaline phosphatase >2.0x ULN; or bilirubin >2.0x ULN.
- Abnormal clotting, as evidenced by PT or PTT >1.5x ULN, or therapeutic/prophylactic anticoagulation.
- Renal impairment, defined as either serum creatinine higher than the institution ULN,or estimated creatinine clearance lower than LLN (i.e. patients should have both normal serum creatinine, and normal estimated creatinine clearance)
- Impaired marrow function, defined as haemoglobin <9.0 g/dL, neutrophils <1.5 x10^9/L, or platelets <100 x10^9/L. Patients may receive a blood transfusion for anaemia to allow entry to the study but should not be transfusion-dependent.
- Left ventricular ejection fraction <50% on echocardiography or MUGA scan.
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- Known metastases of the central nervous system.
- Prior anticancer therapies including tyrosine kinase inhibitors (other than imatinib) not completed within 2 weeks or 5 half-lives of the agent (including known active metabolites) prior to treatment with study drug. Patients receiving imatinib should continue to receive imatinib (400 mg daily) throughout the screening period.
- Clinically important intolerance or safety concerns with prior use of imatinib 400 mg daily.
- Prior treatment with an HSP90 inhibitor.
- Major surgery within 14 days prior to treatment with study drug, or failure to recover from the effects of such surgery.
- Wide field radiotherapy within 4 weeks prior to treatment with study drug, limited field radiation within 2 weeks, or failure to recover from such therapies.
- History of an ischaemic cardiac event or unstable cardiac disease within 3 months of study entry.
- QTc >450 ms using Fredericia's correction.
- Previous malignancy, except for basal cell and squamous cell skin carcinomas or carcinoma of the uterine cervix, unless treated with curative intent more than 2 years prior to study entry.
- Evidence of severe or uncontrolled systemic medical conditions which make it undesirable for the patient to take part in the study, or which could jeopardize protocol compliance. Patients with multiple comorbidities and/or requiring multiple concomitant medications (especially conditions/medications which may impair renal function or predispose to renal impairment) should be discussed with the Astex Medical Monitor at the discretion of the Investigator before enrollment.
- Prior history of infection with HIV, or known active hepatitis B or C viral infection (active screening for viral infections is not required for study entry).
- Significant visual impairment such that in the opinion of the investigator, further minor deterioration would have unacceptable consequences (eg. loss of ability to drive or live at home.
- The Safety Monitoring Committee may add other specific exclusion criteria to enhance the safety of the patients based on emerging safety data.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Johns Hopkins University
Baltimore, Maryland, 21231
Dana-Farber Cancer Institute
Boston, Massachusetts, 02459
Robert H. Lurie Cancer Center of Northwestern University
Chicago, Illinois, 60611
Duke University Medical Center
Durham, North Carolina, 27710
University of Texas MD Anderson Cancer Center
Houston, Texas, 77230-1402
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2412
Oregon Health and Sciences University
Portland, Oregon, 97239
Arizona Cancer Center at UMC North
Tucson, Arizona, 85719
About this study
Official title: An Open-Label, Randomised, Multi-Centre, Phase II Study to Investigate the Safety and Efficacy of AT13387, Either as Monotherapy or in Combination With Imatinib, in Patients With Unresectable and/or Metastatic Malignant GIST Whose Tumour Has Progressed Following Treatment With a Maximum of Three Tyrosine Kinase Inhibitors
The purpose of this study is to investigate if an investigational drug called AT13387 is active against Gastrointestinal Stromal Tumor (GIST) that is resistant to other treatments, and to understand more about the safety of AT13387.
Most subjects in the study will receive AT13387 along with another drug called imatinib (Gleevec). Imatinib is a standard (approved) drug for treating patients with GIST. Some patients may receive AT13387 on its own. As a result, we shall begin to understand the effects of AT13387 given on its own and when combined with imatinib.We shall also find out more about the side-effects of AT13387, and more about how the body breaks down (metabolizes) AT13387.
Read the detailed description
The study consists of 3 parts: Part 1 is a dose escalation phase, Part 2 is a dose expansion phase and Part 3 is either a further dose expansion phase or a randomised phase in which half the patients receive AT13387 monotherapy and half continue to receive AT13387 in combination with imatinib.
All patients will receive AT13387 given by intravenous infusion on Days 1, 8, and 15 of a 28-day cycle. Most patients will also receive imatinib 400 mg by mouth every day.
Patients will have tumour imaging at baseline, and at 2, 4 and 6 months, and then at 2 month intervals until cycle 12, and then 3-monthly thereafter.
Blood samples will be taken to measure plasma drug levels of AT13387 given in combination with imatinib
- Conditions
- Gastrointestinal Stromal Tumor (GIST)
- Being tested
- AT13387 and Imatinib
- Keywords
- GIST, Gastrointestinal Stromal Tumor, unresectable, metastatic, AT13387, Astex, Gleevec, Imatinib
- Medical subject headings
- Gastrointestinal Stromal Tumors, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AT13387 and ImatinibDrug
Also called Gleevec
In part 1 pts will receive AT13387 in combination with imatinib. Up to 5 possible dose levels of AT13387 could be evaluated in combination with imatinib 400 mg daily: 120 mg/m2, 150 mg/m2, 180 mg/m2, 220 mg/m2 and 260 mg/m2. AT13387 IV (in the vein) on day 1, 8 and 15 of each 28 day cycle, until progression or unacceptable toxicity develops, in order to establish the recommended phase II combination dose, which will be used in part 2 and/or part 3 of the study.
In part 2 an additional 6-9pts will be treated.
In part 3, provided that sufficient evidence of anti-tumour effect was observed in part 2 (disease stabilisation or reduction in tumour dimensions by RECIST), then an additional 12pts will be treated with AT13387 in combination with imatinib. Alternatively, if combination treatment is found to have excellent efficacy the randomised phase of the study may start so that 12 pts receive AT13387 on its own (monotherapy) and 12 pts receive AT13387 in combination with imatinib.
| Study group | Role | What they receive |
|---|---|---|
| AT13387 and imatinib | Experimental | AT13387 administered on days 1, 8 and 15, imatinib administered daily Receives: Drug: AT13387 and Imatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of reduction/stabilisation of tumour size at 4 months according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria
Measured: 4 months
Secondary outcomes (7)
Rate of reduction/stabilisation of tumour size at 6 months (6-month 'disease control rate' [DCR]), determined according to RECIST version 1.1 criteria.
Measured: 6 months
Progression-free survival at 6 months, and estimated proportion of patients surviving at 6 months.
Measured: 6 months
Objective responses, using RECIST version 1.1 criteria
Measured: 6 months
Changes in pharmacodynamic biomarkers assessed in tumour biopsies and plasma samples, and changes in tumour metabolism by Fludeoxyglucose - Positron emission tomography scans (FDG-PET).
Measured: 6 months
Relationships between KIT and PDGRFA tumour mutational status, changes in tumour dimensions, and exploratory pharmacodynamic biomarkers.
Measured: 6 months
Pharmacokinetic profile of AT13387 given in combination with imatinib.
Measured: 6 months
Treatment emergent adverse events, classified by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
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 posted11 Feb 2011 (estimated)
- Study startMar 2011
- Primary completionApr 2013
- Study completionJul 2014
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 Gastrointestinal Stromal Tumor (GIST)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astex Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01294202
- Sponsor's protocol ID
- AT13387/0002
- Status last verified
- Aug 2024
- First submitted
- 10 Feb 2011
- Last updated
- 2 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
Publications
Wagner AJ, Agulnik M, Heinrich MC, Mahadevan D, Riedel RF, von Mehren M, Trent J, Demetri GD, Corless CL, Yule M, Lyons JF, Oganesian A, Keer H. Dose-escalation study of a second-generation non-ansamycin HSP90 inhibitor, onalespib (AT13387), in combination with imatinib in patients with metastatic gastrointestinal stromal tumour. Eur J Cancer. 2016 Jul;61:94-101. doi: 10.1016/j.ejca.2016.03.076. Epub 2016 May 5.
PubMed 27156227
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Randomised, Multi-Centre, Phase II Study to Investigate the Safety and Efficacy of AT13387, Either as Monotherapy or in Combination With Imatinib, in Patients With Unresectable and/or Metastatic Malignant GIST Whose Tumour Has Progressed Following Treatment With a Maximum of Three Tyrosine Kinase Inhibitors
- ClinicalTrials.gov ID
- NCT01294202
- Acronym / sponsor ID
- AT13387/0002
- Conditions
- Gastrointestinal Stromal Tumor (GIST)
- Keywords
- GIST, Gastrointestinal Stromal Tumor, unresectable, metastatic, AT13387, Astex, Gleevec, Imatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Astex Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Mar 2011
- Primary completion
- Apr 2013 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 11 Feb 2011 (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 investigate if an investigational drug called AT13387 is active against Gastrointestinal Stromal Tumor (GIST) that is resistant to other treatments, and to understand more about the safety of AT13387.
Most subjects in the study will receive AT13387 along with another drug called imatinib (Gleevec). Imatinib is a standard (approved) drug for treating patients with GIST. Some patients may receive AT13387 on its own. As a result, we shall begin to understand the effects of AT13387 given on its own and when combined with imatinib.We shall also find out more about the side-effects of AT13387, and more about how the body breaks down (metabolizes) AT13387.
Detailed description
The study consists of 3 parts: Part 1 is a dose escalation phase, Part 2 is a dose expansion phase and Part 3 is either a further dose expansion phase or a randomised phase in which half the patients receive AT13387 monotherapy and half continue to receive AT13387 in combination with imatinib.
All patients will receive AT13387 given by intravenous infusion on Days 1, 8, and 15 of a 28-day cycle. Most patients will also receive imatinib 400 mg by mouth every day.
Patients will have tumour imaging at baseline, and at 2, 4 and 6 months, and then at 2 month intervals until cycle 12, and then 3-monthly thereafter.
Blood samples will be taken to measure plasma drug levels of AT13387 given in combination with imatinib
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AT13387 and imatinib | Experimental | Drug: AT13387 and ImatinibAT13387 administered on days 1, 8 and 15, imatinib administered daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Ability to understand the risks of the study and to provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations).
- Age 18 years or older.
- Unresectable and/or metastatic malignant GIST with objective progression of disease following treatment with a maximum of 3 tyrosine kinase inhibitors (TKIs) including imatinib. To clarify, it is the number of TKIs - up to a maximum of three agents, including imatinib - that is the criterion for entry, not the number of prior courses of TKI treatment.
- Measurable disease.
- ECOG performance status 0 or 1.
Key exclusion criteria (19 listed)
- Pregnancy or lactation (women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to commencing treatment ). Male and female patients of childbearing potential must use appropriate birth control (abstinence, barrier methods, oral contraceptives and/or intrauterine devices) during the entire duration of the study, or the patient must be surgically sterile (with documentation in the patient's medical records).
- Impaired liver function, as evidenced by prior liver segmentectomy or hemi-hepatectomy; or alanine or aspartate aminotransferase (ALAT/ASAT) >2.5x ULN; or alkaline phosphatase >2.0x ULN; or bilirubin >2.0x ULN.
- Abnormal clotting, as evidenced by PT or PTT >1.5x ULN, or therapeutic/prophylactic anticoagulation.
- Renal impairment, defined as either serum creatinine higher than the institution ULN,or estimated creatinine clearance lower than LLN (i.e. patients should have both normal serum creatinine, and normal estimated creatinine clearance)
- Impaired marrow function, defined as haemoglobin <9.0 g/dL, neutrophils <1.5 x10^9/L, or platelets <100 x10^9/L. Patients may receive a blood transfusion for anaemia to allow entry to the study but should not be transfusion-dependent.
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 |
|---|---|---|
| AT13387 and ImatinibAlso: GleevecIn part 1 pts will receive AT13387 in combination with imatinib. Up to 5 possible dose levels of AT13387 could be evaluated in combination with imatinib 400 mg daily: 120 mg/m2, 150 mg/m2, 180 mg/m2, 220 mg/m2 and 260 mg/m2. AT13387 IV (in the vein) on day 1, 8 and 15 of each 28 day cycle, until progression or unacceptable toxicity develops, in order to establish the recommended phase II combination dose, which will be used in part 2 and/or part 3 of the study. In part 2 an additional 6-9pts will be treated. In part 3, provided that sufficient evidence of anti-tumour effect was observed in part 2 (disease stabilisation or reduction in tumour dimensions by RECIST), then an additional 12pts will be treated with AT13387 in combination with imatinib. Alternatively, if combination treatment is found to have excellent efficacy the randomised phase of the study may start so that 12 pts receive AT13387 on its own (monotherapy) and 12 pts receive AT13387 in combination with imatinib. | Drug | AT13387 and imatinib |
Primary outcome
Rate of reduction/stabilisation of tumour size at 4 months according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria
Time frame: 4 months
7 secondary outcomes
Rate of reduction/stabilisation of tumour size at 6 months (6-month 'disease control rate' [DCR]), determined according to RECIST version 1.1 criteria.
Time frame: 6 months
Progression-free survival at 6 months, and estimated proportion of patients surviving at 6 months.
Time frame: 6 months
Objective responses, using RECIST version 1.1 criteria
Time frame: 6 months
Changes in pharmacodynamic biomarkers assessed in tumour biopsies and plasma samples, and changes in tumour metabolism by Fludeoxyglucose - Positron emission tomography scans (FDG-PET).
Time frame: 6 months
Relationships between KIT and PDGRFA tumour mutational status, changes in tumour dimensions, and exploratory pharmacodynamic biomarkers.
Time frame: 6 months
Pharmacokinetic profile of AT13387 given in combination with imatinib.
Time frame: 6 months
Treatment emergent adverse events, classified by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Time frame: 6 months
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 2 Aug 2024.
- Derived from this study: PubMed 27156227Wagner AJ, Agulnik M, Heinrich MC, Mahadevan D, Riedel RF, von Mehren M, Trent J, Demetri GD, Corless CL, Yule M, Lyons JF, Oganesian A, Keer H. Dose-escalation study of a second-generation non-ansamycin HSP90 inhibitor, onalespib (AT13387), in combination with imatinib in patients with metastatic gastrointestinal stromal tumour. Eur J Cancer. 2016 Jul;61:94-101. doi: 10.1016/j.ejca.2016.03.076. Epub 2016 May 5.
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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.
The record lists no contact. Use the official record to reach the sponsor.
8 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 AT13387 and Imatinib in people with Gastrointestinal Stromal Tumor (GIST), run by Astex Pharmaceuticals, Inc. at 8 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 7 inclusion and 19 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 2 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 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?
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?
Rate of reduction/stabilisation of tumour size at 4 months according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria (time frame: 4 months). 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 NCT01294202, 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 2 Aug 2024.