Gastrointestinal Stromal TumorsPhase 1NCT00276302
Safety Study of IPI-504 in Patients With Gastrointestinal Stromal Tumors (GIST) or Soft Tissue Sarcomas (STS)
A Phase 1 study testing IPI-504 in people with Gastrointestinal Stromal Tumors and Soft Tissue Sarcomas, run by Infinity Pharmaceuticals, Inc. at 5 sites in 2 countries.
Trial summary
The primary objectives of the study are: Determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies Recommend a dose for subsequent studies of IPI-504 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumors, Soft Tissue Sarcomas
- What is being tested?
- IPI-504
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Dec 2005to Nov 2010
- 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
- Pathologically confirmed diagnosis of GIST or STS
- Failed prior therapies
- ECOG performance status of 0-2
- Ability to adhere to the study visit schedule and all protocol requirements
Who cannot join
- Previous treatment with 17-AAG, DMAG, or other known Hsp90 inhibitor
- Participation in any investigational drug study or treatment with any other kinase inhibitor therapy within 2 weeks preceding start of treatment
- Concurrent radiation therapy is not permitted
- Concurrent treatment with any agent that alters CYP3A activity
- Concurrent treatment with any agent that may prolong the QTc interval
- Myocardial infarction or active ischemic heart disease within 6 months
Show all 16Show fewer
- History of arrhythmia
- Baseline QTc >450
- Grade 3 or greater peripheral neuropathy
- Renal insufficiency, serum creatinine >1.5 x ULN
- Platelets < 100,000 mm3
- AST and / or ALT > 2.5 x ULN
- ANC <1,500 cells/mm3
- Alkaline phosphatase > 2.5 x ULN
- Amylase and lipase > 1.5 x ULN
- Hemoglobin < 9.0 g/dL
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
University of Michigan Hosptials
Ann Arbor, Michigan, 48109
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Premiere Oncology
Santa Monica, California, 90404
Premiere Oncology
Scottsdale, Arizona, 85260
About this study
Official title: A Phase 1, Safety Assessment and Pharmacokinetic Study of IPI-504 in Patients With Either Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) or Advanced or Metastatic Soft Tissue Sarcomas (STS)
The primary objectives of the study are:
- Determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies
- Recommend a dose for subsequent studies of IPI-504
Read the detailed description
IPI-504 is a novel, water-soluble analog of 17-AAG and a potent inhibitor of Hsp90. Hsp90's role in the cell is to control the proper folding, function, and viability of various "client" proteins. Many of these client proteins (such as AKT, Her-2, Bcr-Abl, PDGFR-α, and c-Kit) are oncoproteins or important cell signaling proteins. In patients with GIST, mutations in the tyrosine kinase receptor Kit play a critical role in the pathogenesis of this disease. Inhibition of Kit signaling with the tyrosine kinase inhibitor Imatinib (IM) is a very effective treatment for GIST patients. However, new mutations arise in Kit conferring resistance to IM treatment which results in disease progression. Kit is a client protein of Hsp90 and is sensitive to IPI-504. In Soft Tissue Sarcomas, there may be genetic abnormalities that lead to the expression of certain proteins that drive the growth of cancer. These cancer-driving proteins may be stimulated by HSP90. This provides a scientific rationale for Phase 1 clinical testing of IPI-504 in patients with advanced GIST and STS who have failed prior therapies.
- Being tested
- IPI-504
- Medical subject headings
- Gastrointestinal Stromal Tumors, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IPI-504Drug
IV administration of IPI-504 for 21-day cycles. Two different schedules of treatment will be tested. On Schedule A, doses occur on Days 1, 4, 8, and 11 followed by 10 days with no study drug administration. On Schedule B, doses occur on Days 1, 4, 8, 11, 15, and 18, or twice weekly for 3 weeks continuously.
For both Schedule A and B doses will be administered ≥ 72 hours apart.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Schedule A: Doses occur on Days 1, 4, 8, and 11 followed by 10 days with no study drug administration. Receives: Drug: IPI-504 |
| 2 | Experimental | Schedule B: Doses occur on Days 1, 4, 8, 11, 15, and 18 (twice weekly for 3 weeks continuously). Receives: Drug: IPI-504 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies
Measured: 18 months
To recommend a dose for subsequent studies of IPI-504
Measured: 18 months
Secondary outcomes (3)
To examine the pharmacokinetic (PK) parameters of IPI-504 in GIST and STS patients
Measured: 18 months
To assess in a preliminary way the potential anti-tumor activity of IPI-504 in GIST and STS.
Measured: 18 months
To explore potential pharmacodynamic (PD) markers of biologic activity of IPI-504 in GIST and STS.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2006 (estimated)
- Study startDec 2005
- Primary completionNov 2010
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal Stromal TumorsStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Infinity Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- George D Demetri, MD, PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00276302
- Sponsor's protocol ID
- IPI-504-02
- Status last verified
- Jan 2011
- First submitted
- 11 Jan 2006
- Last updated
- 6 Jan 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Safety Assessment and Pharmacokinetic Study of IPI-504 in Patients With Either Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) or Advanced or Metastatic Soft Tissue Sarcomas (STS)
- ClinicalTrials.gov ID
- NCT00276302
- Acronym / sponsor ID
- IPI-504-02
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Infinity Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2005
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 13 Jan 2006 (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 primary objectives of the study are:
- Determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies
- Recommend a dose for subsequent studies of IPI-504
Detailed description
IPI-504 is a novel, water-soluble analog of 17-AAG and a potent inhibitor of Hsp90. Hsp90's role in the cell is to control the proper folding, function, and viability of various "client" proteins. Many of these client proteins (such as AKT, Her-2, Bcr-Abl, PDGFR-α, and c-Kit) are oncoproteins or important cell signaling proteins. In patients with GIST, mutations in the tyrosine kinase receptor Kit play a critical role in the pathogenesis of this disease. Inhibition of Kit signaling with the tyrosine kinase inhibitor Imatinib (IM) is a very effective treatment for GIST patients. However, new mutations arise in Kit conferring resistance to IM treatment which results in disease progression. Kit is a client protein of Hsp90 and is sensitive to IPI-504. In Soft Tissue Sarcomas, there may be genetic abnormalities that lead to the expression of certain proteins that drive the growth of cancer. These cancer-driving proteins may be stimulated by HSP90. This provides a scientific rationale for Phase 1 clinical testing of IPI-504 in patients with advanced GIST and STS who have failed prior therapies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: IPI-504Schedule A: Doses occur on Days 1, 4, 8, and 11 followed by 10 days with no study drug administration. |
| 2 | Experimental | Drug: IPI-504Schedule B: Doses occur on Days 1, 4, 8, 11, 15, and 18 (twice weekly for 3 weeks continuously). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Pathologically confirmed diagnosis of GIST or STS
- Failed prior therapies
- ECOG performance status of 0-2
- Ability to adhere to the study visit schedule and all protocol requirements
Key exclusion criteria (16 listed)
- Previous treatment with 17-AAG, DMAG, or other known Hsp90 inhibitor
- Participation in any investigational drug study or treatment with any other kinase inhibitor therapy within 2 weeks preceding start of treatment
- Concurrent radiation therapy is not permitted
- Concurrent treatment with any agent that alters CYP3A activity
- Concurrent treatment with any agent that may prolong the QTc interval
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 |
|---|---|---|
| IPI-504IV administration of IPI-504 for 21-day cycles. Two different schedules of treatment will be tested. On Schedule A, doses occur on Days 1, 4, 8, and 11 followed by 10 days with no study drug administration. On Schedule B, doses occur on Days 1, 4, 8, 11, 15, and 18, or twice weekly for 3 weeks continuously. For both Schedule A and B doses will be administered ≥ 72 hours apart. | Drug | 1, 2 |
Primary outcome
To determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies
Time frame: 18 months
To recommend a dose for subsequent studies of IPI-504
Time frame: 18 months
3 secondary outcomes
To examine the pharmacokinetic (PK) parameters of IPI-504 in GIST and STS patients
Time frame: 18 months
To assess in a preliminary way the potential anti-tumor activity of IPI-504 in GIST and STS.
Time frame: 18 months
To explore potential pharmacodynamic (PD) markers of biologic activity of IPI-504 in GIST and STS.
Time frame: 18 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 6 Jan 2011.
- Gist Support InternationalLink provided by the sponsor.
- Life Raft GroupLink provided by the sponsor.
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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.
George D Demetri, MD, PhD principal investigator
Dana-Farber Cancer Institute
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IPI-504 in people with Gastrointestinal Stromal Tumors and Soft Tissue Sarcomas, run by Infinity Pharmaceuticals, Inc. at 5 sites in 2 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 4 inclusion and 16 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 6 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Canada. 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?
To determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies (time frame: 18 months). 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?
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 6 Jan 2011.