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

This study has been terminated.
(Based on Independent Data Monitoring Committee (IDMC) recommendation.)
Sponsor:
Collaborators:
MedImmune LLC
AstraZeneca
Information provided by (Responsible Party):
Infinity Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00688766
First received: May 29, 2008
Last updated: December 7, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Gastrointestinal Stromal Tumors
Drug: retaspimycin hydrochloride (IPI-504)
Drug: placebo
Other: Best supportive care
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Infinity Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Compare the progression free survival (PFS) in both study arms [ Time Frame: Multiple timepoints ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Compare the disease control rate (DCR) in both arms [ Time Frame: Multiple timepoints ] [ Designated as safety issue: No ]
  • Compare the time to progression (TTP) in both arms [ Time Frame: Multiple timepoints ] [ Designated as safety issue: No ]
  • Compare the overall survival (OS) in both arms [ Time Frame: Continuous ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 47
Study Start Date: August 2008
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IPI-504
retaspimycin hydrochloride (IPI-504) plus best supportive care
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.
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.
Placebo Comparator: Placebo
Placebo plus best supportive care
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00688766

Sponsors and Collaborators
Infinity Pharmaceuticals, Inc.
MedImmune LLC
AstraZeneca
Investigators
Study Director: Pedro Santabarbara, M.D. Infinity Pharmaceuticals, Inc.
Principal Investigator: George Demetri, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Infinity Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00688766     History of Changes
Other Study ID Numbers: IPI-504-06
Study First Received: May 29, 2008
Last Updated: December 7, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Infinity Pharmaceuticals, Inc.:
GIST
Metastatic and/or Unresectable Gastrointestinal Stromal

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Imatinib
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014