- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00688766
Study Evaluating IPI-504 in Patients With Gastrointestinal Stromal Tumors (GIST) Following Failure of at Least Imatinib and Sunitinib
A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study Evaluating the Efficacy and Safety of IPI-504 in Patients With Metastatic and/or Unresectable GIST Following Failure of at Least Imatinib and Sunitinib
IPI-504-06 is a Phase 3, randomized, double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of IPI-504 as compared to placebo in patients with metastatic and/or unresectable GIST following failure of at least imatinib and sunitinib.
Approximately 195 patients will be randomized using a 2:1 ratio to receive either IPI-504 (N=130) or placebo (N=65). Upon unblinding, patients receiving either IPI-504 or placebo may receive IPI-504 in the open-label portion of the study if defined inclusion criteria are met.
Early and frequent imaging timepoints (Weeks 2, 5, 8, 14 and every 6 weeks thereafter) are incorporated into this study to capture progression events and limit patient exposure to ineffective agents.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- At least 18 years of age at the time of study randomization.
- Histologically confirmed metastatic and/or unresectable GIST.
- Measurable disease on CT or MRI as defined by RECIST.
- Documented radiographic progression or intolerance to imatinib and sunitinib.
- Clinical failure of the most recent prior therapy for GIST. Note: There is no limit to the number of prior therapies a patient may have received.
- Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1.
- Hemoglobin ≥ 8.0 g/dL (80 g/L).
- Absolute Neutrophil Count ≥ 1500/µL (1.5 x 109/L).
- Platelets ≥ 100,000 /µL (100 x 109/L).
- ALT and AST ≤ 2.5 x upper limit of normal (ULN), or ≤ 5.0 x ULN if considered secondary to liver metastases.
- Alkaline phosphatase ≤ 2.5 x ULN, or ≤ 5.0 x ULN if considered secondary to liver metastases.
- Serum bilirubin ≤ 1.5 x ULN.
- PT and PTT ≤ 1.5 x ULN unless the patient is receiving warfarin. If the patient is receiving warfarin, the INR must be within therapeutic range.
- Serum creatinine ≤ 1.5 x ULN.
Exclusion Criteria:
- Previous administration of other known heat shock protein 90 (Hsp90) inhibitors.
- Surgery, radiotherapy, or lesion ablative procedure to the only area of measurable disease.
- Initiation or discontinuation of concurrent medication that is a potent CYP3A inhibitor less than 2 weeks prior to administration of IPI-504 or placebo.
- History of any of the following within the last 6 months: cardiac disease such as acute coronary syndrome or unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, cirrhotic liver disease, cerebrovascular accident, or any other significant co-morbid condition or disease which, in the judgment of the investigator, would place the patient at undue risk or interfere with the study.
- Grade 3 or 4 hemorrhagic event within the last 6 months.
- Known human immunodeficiency virus positivity.
- Sinus bradycardia (resting heart rate < 50 bpm) secondary to intrinsic conduction system disease.
- QTcF ≥ 470 milliseconds, or previous history of clinically significant QTc prolongation while taking other medications.
- History of prior malignancies within the past 3 years other than non-melanomatous skin cancers that have been controlled, prostate cancer that has been treated and has not recurred, non-muscle-invasive bladder cancer, and carcinoma in situ of the cervix.
- Active or recent history (within 3 months) of keratitis or keratoconjunctivitis confirmed by ophthalmology or optometry exam.
- Presence of Left Bundle Branch Block, Right Bundle Branch Block plus left anterior hemiblock, bifascicular block, or 3rd degree heart block. This does not include patients with a history of these events with adequate control by pacemaker.
- Known CNS metastases.
- Women who are pregnant or lactating.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: IPI-504
retaspimycin hydrochloride (IPI-504) plus best supportive care
|
IPI-504 is a novel small molecule inhibitor of heat shock protein 90 (Hsp90).
Patients will receive 400 mg/m2 of IPI-504 as a 30-minute IV infusion twice weekly for 2 weeks followed by 1 week off.
Best supportive care will be according to institutional standard, but will not include administration of systemic cancer-specific therapies including chemotherapies, biologic therapies, investigational therapies, TKIs (e.g., imatinib, sunitinib, nilotinib, dasatinib), or local therapies such as surgery, radiotherapy, or lesion ablative therapies.
|
PLACEBO_COMPARATOR: Placebo
Placebo plus best supportive care
|
Best supportive care will be according to institutional standard, but will not include administration of systemic cancer-specific therapies including chemotherapies, biologic therapies, investigational therapies, TKIs (e.g., imatinib, sunitinib, nilotinib, dasatinib), or local therapies such as surgery, radiotherapy, or lesion ablative therapies.
Patients will receive a 30-minute IV infusion twice weekly for 2 weeks followed by 1 week off.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Compare the progression free survival (PFS) in both study arms
Time Frame: Multiple timepoints
|
Multiple timepoints
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Compare the disease control rate (DCR) in both arms
Time Frame: Multiple timepoints
|
Multiple timepoints
|
Compare the time to progression (TTP) in both arms
Time Frame: Multiple timepoints
|
Multiple timepoints
|
Compare the overall survival (OS) in both arms
Time Frame: Continuous
|
Continuous
|
Evaluate the safety and tolerability of IPI-504 in this patient population
Time Frame: Signing of the informed consent to 30 days after discontinuation of drug
|
Signing of the informed consent to 30 days after discontinuation of drug
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Pedro Santabarbara, M.D., Infinity Pharmaceuticals, Inc.
- Principal Investigator: George Demetri, MD, Dana-Farber Cancer Institute
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IPI-504-06
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Gastrointestinal Stromal Tumors
-
Washington University School of MedicineNorthwestern UniversityCompletedGastrointestinal Stromal Cell Tumors | Foregut Subepithelial LesionsUnited States
-
Centre Leon BerardGustave Roussy, Cancer Campus, Grand ParisCompletedSarcoma | Gastro-intestinal Stromal Tumors (GIST)France
-
AB ScienceCompletedGastro Intestinal Stromal TumorFrance
-
Centre Leon BerardRecruiting
-
Institut BergoniéFrench Sarcoma GroupRecruitingGastro Intestinal Stromal TumorFrance
-
University Medical Center GroningenDutch Cancer SocietyRecruitingGastro-intestinal Stromal TumorNetherlands
-
AB ScienceCompletedGastro-intestinal Stromal TumoursFrance
-
National University Hospital, SingaporeUnknownAsian Patients With Advanced Gastro-intestinal Stromal Tumors (GIST) Treated With ImatinibSingapore
-
Blueprint Medicines CorporationCompletedGastrointestinal Stromal Tumors (GIST) | Other Relapsed or Refractory Solid TumorsUnited States, United Kingdom, France, Korea, Republic of, Belgium, Germany, Italy, Netherlands, Poland, Spain
-
Institut BergoniéCompletedAdvanced Gastrointestinal Stromal TumorsFrance
Clinical Trials on retaspimycin hydrochloride (IPI-504)
-
Infinity Pharmaceuticals, Inc.CompletedNon-small Cell Lung CancerUnited States
-
Massachusetts General HospitalDana-Farber Cancer Institute; Infinity Pharmaceuticals, Inc.TerminatedLung Cancer | Stage IV Lung Cancer | Stage IIIb Lung CancerUnited States
-
Infinity Pharmaceuticals, Inc.CompletedGastrointestinal Stromal Tumors | Soft Tissue SarcomasUnited States, Canada
-
Infinity Pharmaceuticals, Inc.TerminatedMetastatic MelanomaUnited States
-
Infinity Pharmaceuticals, Inc.Completed
-
Infinity Pharmaceuticals, Inc.WithdrawnDedifferentiated LiposarcomaUnited States
-
Infinity Pharmaceuticals, Inc.CompletedMultiple MyelomaUnited States
-
MedImmune LLCWithdrawnBreast CancerUnited States
-
Infinity Pharmaceuticals, Inc.CompletedProstatic Neoplasms | Prostate Cancer | Cancer of the ProstateUnited States
-
Infinity Pharmaceuticals, Inc.CompletedNon Small Cell Lung CancerUnited States, Hungary, Taiwan, Korea, Republic of, Russian Federation, Romania