Gastrointestinal Stromal TumorPhase 2NCT01404650
Study of Hsp90 Inhibitor AUY922 for the Treatment of Patients With Refractory Gastrointestinal Stromal Tumor
A Phase 2 study testing AUY922 in people with Gastrointestinal Stromal Tumor, run by SCRI Development Innovations, LLC at 8 sites in United States.
Trial summary
This is a multicenter, non-randomized, single agent, Phase II study of AUY922 in patients with refractory Gastrointestinal Stromal Tumor (GIST). The primary endpoint of this study is to determine progression-free survival (PFS) for patients with GIST receiving AUY922 intravenously (IV) on Days 1, 8, and 15 of a 21-day… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumor
- What is being tested?
- AUY922
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 8 sitesUnited States
- Study dates
- Dec 2011to Feb 2015
- 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
- Pts with histologically-confirmed metastatic or unresectable GIST who have progressed on, are intolerant of, or are not a candidate for imatinib and sunitinib therapy. Pts must not have received prior treatment with Hsp90 inhibitors.
- Must have an ECOG Performance Status of 0-1.
- Must have a life expectancy of ≥3 mos.
- Must have at least one unidimensional measurable lesion definable by MRI or CT scan. Disease must be measurable per RECIST v1.1.
- Must have normal serum phosphorus and magnesium ≥ the lower limit of normal prior to trial entry.
- Normal bone marrow function defined as: ANC ≥1500/μL Hgb ≥9 g/dL Plt ≥100,000/L
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- Adequate hepatic function defined as: AST or ALT and ALP must be 2.5 x ULN, or ≤5 x ULN in pts with liver mets Total bilirubin ≤1.5 x the institutional ULN
- Renal function defined as: Serum creatinine ≤1.5 x ULN or 24-hour CrCl 50 mL/min
- Women of childbearing potential (WOCP) must have a negative serum or urine pregnancy test performed ≤7 days prior to start of treatment.
- Must be accessible for treatment and follow-up.
- Must be able to understand the investigational nature of this study and give written informed consent prior to study entry
Who cannot join
- Currently receiving or have received cancer therapies ≤21 days of initiating study therapy. For pts receiving small molecule targeted therapy, study treatment may begin ≥21 days after last dose or ≥5 half lives of previous treatment, whichever is shorter. The patient must have recovered from or come to a new chronic stable baseline from all treatment-related toxicities.
- Use of any non-approved or investigational agent ≤30 days of administration of the first dose of study drug. Pts may not receive any other investigational or anti-cancer treatments while participating in this study.
- Uncontrolled brain mets. Pts with treated brain mets (resection or radiotherapy) are eligible if brain mets have responded to treatment as documented by CT or MRI scan obtained at ≥2 wks after completion of RT, neurologic symptoms are absent, and steroids have been discontinued.
- Treatment with therapeutic doses of coumadin-type anticoagulants (maximum daily dose of 1 mg allowed for port line patency permitted).
- Impaired cardiac function with any one of the following: History (or family history) of prolong QT syndrome. Mean QTc ≥450 msec on baseline ECG. History of clinically manifested IHD ≤6 mos prior to study start. History of heart failure or any history of left ventricular (LV) dysfunction (LVEF ≤45%) by MUGA or ECHO. Clinically significant ECG abnormalities including 1 or more of the following: left bundle branch block, right bundle branch block with left anterior hemiblock. ST segment elevation or depression >1 mm, or 2nd (Mobitz II) or 3rd degree AV block. History or presence of A-Fib, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes. Other clinically significant heart disease. Clinically significant resting bradycardia (<50 beats per minute). Currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval or inducing Torsades de Pointes and cannot be switched to an alternative drug or discontinued prior to commencing AUY922. Obligate use of a cardiac pacemaker.
- Known diagnosis of HIV, Hep C virus, or acute or chronic Hep B infection.
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- Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
- Women who are pregnant or lactating.
- Any condition that would prevent patient comprehension of the nature of, and risk associated with, the study, and the inability to comply with study and/or follow-up procedures.
- Other malignancies ≤3 years, with the exception of adequately treated basal or squamous cell carcinomas of the skin, carcinoma in situ of the cervix, or localized prostate cancer with a current PSA of <1.0 mg/dL on 2 successive evaluations, at least 3 mos apart, with the most recent evaluation no more than 4 wks prior to entry.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Florida Cancer Specialists-South
Fort Myers, Florida, 33916
Research Medical Center
Kansas City, Missouri, 64132
Tennessee Oncology
Nashville, Tennessee, 37203
Yale School of Medicine
New Haven, Connecticut, 06520
Nebraska Methodist Hospital
Omaha, Nebraska, 68114
Florida Hospital Cancer Institute
Orlando, Florida, 32804
Woodlands Medical Center
Pensacola, Florida, 32503
Florida Cancer Specialists-North
St. Petersburg, Florida, 33705
About this study
Official title: A Phase II Study of Hsp90 Inhibitor AUY922 for the Treatment of Patients With Refractory Gastrointestinal Stromal Tumor
This is a multicenter, non-randomized, single agent, Phase II study of AUY922 in patients with refractory Gastrointestinal Stromal Tumor (GIST). The primary endpoint of this study is to determine progression-free survival (PFS) for patients with GIST receiving AUY922 intravenously (IV) on Days 1, 8, and 15 of a 21-day treatment cycle with restaging at 6 and 12 weeks and then every 9 weeks thereafter. Patients may continue treatment until evidence of disease progression.
Read the detailed description
Gastrointestinal stromal tumors (GIST) are common sarcomas that arise in the gastrointestinal tract. Sunitinib (Pfizer) and imatinib (Novartis) are FDA-approved for treatment of patients with GIST. However, patients with advanced or refractory GIST who are resistant to these agents eventually experience disease progression or death. Heat shock protein-90 (Hsp90) is a substance found in various malignancies that encourages tumor cells to grow and survive. As an inhibitor of Hsp90, AUY922 may decrease growth of tumor cells that were resistant to prior therapies. This study investigates AUY922 monotherapy as treatment for patients who either progressed on, or were resistant to, imatinib and sunitinib.
- Conditions
- Gastrointestinal Stromal Tumor
- Being tested
- AUY922
- Keywords
- GIST, Refractory, Gastrointestinal, Stromal, Tumor
- Medical subject headings
- Gastrointestinal Stromal Tumors, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AUY922Drug
AUY922: 70 mg/m2 IV over 60 minutes on Days 1, 8, and 15 of each cycle. Treatment cycles will be repeated every 21 days. Patients will be evaluated for response at 6 and 12 weeks and then every 9 weeks (i.e., every 3 cycles) thereafter. Patients may continue treatment until evidence of disease progression.
| Study group | Role | What they receive |
|---|---|---|
| AUY922 | Experimental | Not described Receives: Drug: AUY922 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS)
Measured from time of randomization until objective tumor progression or death; assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Progressive disease (PD) defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest (nadir) sum since the treatment started, or the appearance of one or more new lesions.
Measured: At 6 and 12 weeks then every 9 weeks thereafter until progression or intolerable toxicity, up to 4 years.
Secondary outcomes (3)
Response Rate (RR)
Defined as the proportion of complete and partial responses, assessed per RECIST v1.1. Complete response (CR) defined as a disappearance of all lesions; partial response (PR) defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking the baseline sum LD as reference. Stable Disease (SD) defined as neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for progressive disease, taking as reference the smallest (nadir) sum LD since start of treatment.
Measured: At 6 and 12 weeks then every 9 weeks thereafter until progressive disease or intolerable toxicity, for up to 4 years.
Overall Survival (OS)
Evidence of survival was obtained by clinic visit or telephone contact from the time of first dose until death from any cause.
Measured: Every 3 months until patient death or lost to follow-up, for up to 4 years.
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Worst toxicity grades per patient were tabulated for select adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 4.0
Measured: Days 1, 8 and 15 of each 21-day cycle plus 30 days after treatment discontinuation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2011 (estimated)
- Study startDec 2011
- Primary completionFeb 2015
- Study completionFeb 2015
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 Gastrointestinal Stromal TumorStudies 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
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Johanna Bendell, MD, Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01404650
- Sponsor's protocol ID
- SCRI GI 148
- Status last verified
- Aug 2016
- First submitted
- 21 Jul 2011
- Last updated
- 4 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Hsp90 Inhibitor AUY922 for the Treatment of Patients With Refractory Gastrointestinal Stromal Tumor
- ClinicalTrials.gov ID
- NCT01404650
- Acronym / sponsor ID
- SCRI GI 148
- Conditions
- Gastrointestinal Stromal Tumor
- Keywords
- GIST, Refractory, Gastrointestinal, Stromal, Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Dec 2011
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 28 Jul 2011 (estimated)
- Results
- Posted 4 Oct 2016
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 multicenter, non-randomized, single agent, Phase II study of AUY922 in patients with refractory Gastrointestinal Stromal Tumor (GIST). The primary endpoint of this study is to determine progression-free survival (PFS) for patients with GIST receiving AUY922 intravenously (IV) on Days 1, 8, and 15 of a 21-day treatment cycle with restaging at 6 and 12 weeks and then every 9 weeks thereafter. Patients may continue treatment until evidence of disease progression.
Detailed description
Gastrointestinal stromal tumors (GIST) are common sarcomas that arise in the gastrointestinal tract. Sunitinib (Pfizer) and imatinib (Novartis) are FDA-approved for treatment of patients with GIST. However, patients with advanced or refractory GIST who are resistant to these agents eventually experience disease progression or death. Heat shock protein-90 (Hsp90) is a substance found in various malignancies that encourages tumor cells to grow and survive. As an inhibitor of Hsp90, AUY922 may decrease growth of tumor cells that were resistant to prior therapies. This study investigates AUY922 monotherapy as treatment for patients who either progressed on, or were resistant to, imatinib and sunitinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AUY922 | Experimental | Drug: AUY922 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Pts with histologically-confirmed metastatic or unresectable GIST who have progressed on, are intolerant of, or are not a candidate for imatinib and sunitinib therapy. Pts must not have received prior treatment with Hsp90 inhibitors.
- Must have an ECOG Performance Status of 0-1.
- Must have a life expectancy of ≥3 mos.
- Must have at least one unidimensional measurable lesion definable by MRI or CT scan. Disease must be measurable per RECIST v1.1.
- Must have normal serum phosphorus and magnesium ≥ the lower limit of normal prior to trial entry.
Key exclusion criteria (10 listed)
- Currently receiving or have received cancer therapies ≤21 days of initiating study therapy. For pts receiving small molecule targeted therapy, study treatment may begin ≥21 days after last dose or ≥5 half lives of previous treatment, whichever is shorter. The patient must have recovered from or come to a new chronic stable baseline from all treatment-related toxicities.
- Use of any non-approved or investigational agent ≤30 days of administration of the first dose of study drug. Pts may not receive any other investigational or anti-cancer treatments while participating in this study.
- Uncontrolled brain mets. Pts with treated brain mets (resection or radiotherapy) are eligible if brain mets have responded to treatment as documented by CT or MRI scan obtained at ≥2 wks after completion of RT, neurologic symptoms are absent, and steroids have been discontinued.
- Treatment with therapeutic doses of coumadin-type anticoagulants (maximum daily dose of 1 mg allowed for port line patency permitted).
- Impaired cardiac function with any one of the following: History (or family history) of prolong QT syndrome. Mean QTc ≥450 msec on baseline ECG. History of clinically manifested IHD ≤6 mos prior to study start. History of heart failure or any history of left ventricular (LV) dysfunction (LVEF ≤45%) by MUGA or ECHO. Clinically significant ECG abnormalities including 1 or more of the following: left bundle branch block, right bundle branch block with left anterior hemiblock. ST segment elevation or depression >1 mm, or 2nd (Mobitz II) or 3rd degree AV block. History or presence of A-Fib, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes. Other clinically significant heart disease. Clinically significant resting bradycardia (<50 beats per minute). Currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval or inducing Torsades de Pointes and cannot be switched to an alternative drug or discontinued prior to commencing AUY922. Obligate use of a cardiac pacemaker.
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 |
|---|---|---|
| AUY922AUY922: 70 mg/m2 IV over 60 minutes on Days 1, 8, and 15 of each cycle. Treatment cycles will be repeated every 21 days. Patients will be evaluated for response at 6 and 12 weeks and then every 9 weeks (i.e., every 3 cycles) thereafter. Patients may continue treatment until evidence of disease progression. | Drug | AUY922 |
Primary outcome
Progression-free Survival (PFS)
Time frame: At 6 and 12 weeks then every 9 weeks thereafter until progression or intolerable toxicity, up to 4 years.
Measured from time of randomization until objective tumor progression or death; assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Progressive disease (PD) defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest (nadir) sum since the treatment started, or the appearance of one or more new lesions.
3 secondary outcomes
Response Rate (RR)
Time frame: At 6 and 12 weeks then every 9 weeks thereafter until progressive disease or intolerable toxicity, for up to 4 years.
Overall Survival (OS)
Time frame: Every 3 months until patient death or lost to follow-up, for up to 4 years.
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Time frame: Days 1, 8 and 15 of each 21-day cycle plus 30 days after treatment discontinuation.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Johanna Bendell, MD study chair
SCRI Development Innovations, LLC
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 AUY922 in people with Gastrointestinal Stromal Tumor, run by SCRI Development Innovations, LLC 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 11 inclusion and 10 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 4 Oct 2016. 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?
Yes. Results are posted in the registry (first posted 4 Oct 2016). 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 (PFS) (time frame: At 6 and 12 weeks then every 9 weeks thereafter until progression or intolerable toxicity, up to 4 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 4 Oct 2016.