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

NCT00688766 | Terminated Phase 3 DMC

• 1 other identifier: IPI-504-06
• Study Type: interventional
• Target: 47
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Gastrointestinal Stromal Tumors

Keywords

GIST; Metastatic and/or Unresectable Gastrointestinal Stromal

Outcome Measures

Primary Outcomes (1)

• Compare the progression free survival (PFS) in both study arms

  Multiple timepoints

Secondary Outcomes (4)

• Compare the disease control rate (DCR) in both arms

  Multiple timepoints

• Compare the time to progression (TTP) in both arms

  Multiple timepoints

• Compare the overall survival (OS) in both arms

  Continuous

• Evaluate the safety and tolerability of IPI-504 in this patient population

  Signing of the informed consent to 30 days after discontinuation of drug

Study Arms (2)

IPI-504

EXPERIMENTAL

retaspimycin hydrochloride (IPI-504) plus best supportive care

Drug: retaspimycin hydrochloride (IPI-504); Other: Best supportive care

Placebo

PLACEBO COMPARATOR

Placebo plus best supportive care

Drug: placebo; Other: Best supportive care

Interventions

retaspimycin hydrochloride (IPI-504) DRUG

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.

IPI-504

placebo DRUG

Patients will receive a 30-minute IV infusion twice weekly for 2 weeks followed by 1 week off.

Placebo

Best supportive care OTHER

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.

IPI-504; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Infinity Pharmaceuticals, Inc.: lead
• MedImmune LLC: collaborator
• AstraZeneca: collaborator

Related Links

• Gist Support International - Patient Advocacy Group
• The Liferaft Group - Patient Advocacy Group

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

tanespimycin

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Study Officials

• Pedro Santabarbara, M.D.

  Infinity Pharmaceuticals, Inc.

  STUDY DIRECTOR

• George Demetri, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2008
• First Posted: June 3, 2008
• Study Start: August 1, 2008
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: December 11, 2012

Record last verified: 2012-12