Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study Evaluating IPI-504 in Patients With Gastrointestinal Stromal Tumors (GIST) Following Failure of at Least Imatinib and Sunitinib

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00688766
Recruitment Status : Terminated (Based on Independent Data Monitoring Committee (IDMC) recommendation.)
First Posted : June 3, 2008
Last Update Posted : December 11, 2012
Sponsor:
Collaborators:
MedImmune LLC
AstraZeneca
Information provided by (Responsible Party):
Infinity Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE May 29, 2008
First Posted Date  ICMJE June 3, 2008
Last Update Posted Date December 11, 2012
Study Start Date  ICMJE August 2008
Actual Primary Completion Date May 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 2, 2008)
Compare the progression free survival (PFS) in both study arms [ Time Frame: Multiple timepoints ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 2, 2008)
  • Compare the disease control rate (DCR) in both arms [ Time Frame: Multiple timepoints ]
  • Compare the time to progression (TTP) in both arms [ Time Frame: Multiple timepoints ]
  • Compare the overall survival (OS) in both arms [ Time Frame: 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating IPI-504 in Patients With Gastrointestinal Stromal Tumors (GIST) Following Failure of at Least Imatinib and Sunitinib
Official Title  ICMJE 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
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Gastrointestinal Stromal Tumors
Intervention  ICMJE
  • Drug: retaspimycin hydrochloride (IPI-504)
    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.
  • Drug: placebo
    Patients will receive a 30-minute IV infusion twice weekly for 2 weeks followed by 1 week off.
  • Other: 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.
Study Arms  ICMJE
  • Experimental: IPI-504
    retaspimycin hydrochloride (IPI-504) plus best supportive care
    Interventions:
    • Drug: retaspimycin hydrochloride (IPI-504)
    • Other: Best supportive care
  • Placebo Comparator: Placebo
    Placebo plus best supportive care
    Interventions:
    • Drug: placebo
    • Other: Best supportive care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 2, 2012)
47
Original Estimated Enrollment  ICMJE
 (submitted: June 2, 2008)
195
Actual Study Completion Date  ICMJE May 2009
Actual Primary Completion Date May 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Australia,   Belgium,   France,   Germany,   Korea, Republic of,   Sweden,   United States
 
Administrative Information
NCT Number  ICMJE NCT00688766
Other Study ID Numbers  ICMJE IPI-504-06
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Infinity Pharmaceuticals, Inc.
Study Sponsor  ICMJE Infinity Pharmaceuticals, Inc.
Collaborators  ICMJE
  • MedImmune LLC
  • AstraZeneca
Investigators  ICMJE
Study Director: Pedro Santabarbara, M.D. Infinity Pharmaceuticals, Inc.
Principal Investigator: George Demetri, MD Dana-Farber Cancer Institute
PRS Account Infinity Pharmaceuticals, Inc.
Verification Date December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP