Clinical trial NCT01404650: Study of Hsp90 Inhibitor AUY922 for the Treatment of Patients With Refractory Gastrointestinal Stromal Tumor
Official title: A Phase II Study of Hsp90 Inhibitor AUY922 for the Treatment of Patients With Refractory Gastrointestinal Stromal Tumor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumor
Keywords: GIST
Refractory
Gastrointestinal
Stromal
Tumor
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2011-07-28
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicenter, non-randomized, single agent, Phase II study of AUY922 in patients with refractory Gastrointestinal Stromal Tumor (GIST). The primary endpoint of this study is to determine progression-free survival (PFS) for patients with GIST receiving AUY922 intravenously (IV) on Days 1, 8, and 15 of a 21-day treatment cycle with restaging at 6 and 12 weeks and then every 9 weeks thereafter. Patients may continue treatment until evidence of disease progression.

Detailed description: Gastrointestinal stromal tumors (GIST) are common sarcomas that arise in the gastrointestinal tract. Sunitinib (Pfizer) and imatinib (Novartis) are FDA-approved for treatment of patients with GIST. However, patients with advanced or refractory GIST who are resistant to these agents eventually experience disease progression or death. Heat shock protein-90 (Hsp90) is a substance found in various malignancies that encourages tumor cells to grow and survive. As an inhibitor of Hsp90, AUY922 may decrease growth of tumor cells that were resistant to prior therapies. This study investigates AUY922 monotherapy as treatment for patients who either progressed on, or were resistant to, imatinib and sunitinib.

Eligibility criteria: Inclusion Criteria:

1. Pts with histologically-confirmed metastatic or unresectable GIST who have progressed on, are intolerant of, or are not a candidate for imatinib and sunitinib therapy. Pts must not have received prior treatment with Hsp90 inhibitors.
2. Must have an ECOG Performance Status of 0-1.
3. Must have a life expectancy of ≥3 mos.
4. Must have at least one unidimensional measurable lesion definable by MRI or CT scan. Disease must be measurable per RECIST v1.1.
5. Must have normal serum phosphorus and magnesium ≥ the lower limit of normal prior to trial entry.
6. Normal bone marrow function defined as: ANC ≥1500/μL Hgb ≥9 g/dL Plt ≥100,000/L
7. Adequate hepatic function defined as: AST or ALT and ALP must be 2.5 x ULN, or ≤5 x ULN in pts with liver mets Total bilirubin ≤1.5 x the institutional ULN
8. Renal function defined as: Serum creatinine ≤1.5 x ULN or 24-hour CrCl 50 mL/min
9. Women of childbearing potential (WOCP) must have a negative serum or urine pregnancy test performed ≤7 days prior to start of treatment.
10. Must be accessible for treatment and follow-up.
11. Must be able to understand the investigational nature of this study and give written informed consent prior to study entry

Exclusion Criteria:

1. Currently receiving or have received cancer therapies ≤21 days of initiating study therapy. For pts receiving small molecule targeted therapy, study treatment may begin ≥21 days after last dose or ≥5 half lives of previous treatment, whichever is shorter. The patient must have recovered from or come to a new chronic stable baseline from all treatment-related toxicities.
2. Use of any non-approved or investigational agent ≤30 days of administration of the first dose of study drug. Pts may not receive any other investigational or anti-cancer treatments while participating in this study.
3. Uncontrolled brain mets. Pts with treated brain mets (resection or radiotherapy) are eligible if brain mets have responded to treatment as documented by CT or MRI scan obtained at ≥2 wks after completion of RT, neurologic symptoms are absent, and steroids have been discontinued.
4. Treatment with therapeutic doses of coumadin-type anticoagulants (maximum daily dose of 1 mg allowed for port line patency permitted).
5. Impaired cardiac function with any one of the following: History (or family history) of prolong QT syndrome. Mean QTc ≥450 msec on baseline ECG. History of clinically manifested IHD ≤6 mos prior to study start. History of heart failure or any history of left ventricular (LV) dysfunction (LVEF ≤45%) by MUGA or ECHO. Clinically significant ECG abnormalities including 1 or more of the following: left bundle branch block, right bundle branch block with left anterior hemiblock. ST segment elevation or depression \>1 mm, or 2nd (Mobitz II) or 3rd degree AV block. History or presence of A-Fib, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes. Other clinically significant heart disease. Clinically significant resting bradycardia (\<50 beats per minute). Currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval or inducing Torsades de Pointes and cannot be switched to an alternative drug or discontinued prior to commencing AUY922. Obligate use of a cardiac pacemaker.
6. Known diagnosis of HIV, Hep C virus, or acute or chronic Hep B infection.
7. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
8. Women who are pregnant or lactating.
9. Any condition that would prevent patient comprehension of the nature of, and risk associated with, the study, and the inability to comply with study and/or follow-up procedures.
10. Other malignancies ≤3 years, with the exception of adequately treated basal or squamous cell carcinomas of the skin, carcinoma in situ of the cervix, or localized prostate cancer with a current PSA of \<1.0 mg/dL on 2 successive evaluations, at least 3 mos apart, with the most recent evaluation no more than 4 wks prior to entry.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: At 6 and 12 weeks then every 9 weeks thereafter until progression or intolerable toxicity, up to 4 years.
Secondary outcomes:
measure: Response Rate (RR)
timeFrame: At 6 and 12 weeks then every 9 weeks thereafter until progressive disease or intolerable toxicity, for up to 4 years.
measure: Overall Survival (OS)
timeFrame: Every 3 months until patient death or lost to follow-up, for up to 4 years.
measure: Number of Patients With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Days 1, 8 and 15 of each 21-day cycle plus 30 days after treatment discontinuation.
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Ft. Myers
country: United States
facility: Florida Cancer Specialists-South
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Pensacola
country: United States
facility: Woodlands Medical Center
state: Florida
city: St. Petersburg
country: United States
facility: Florida Cancer Specialists-North
state: Florida
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
Study officials:
affiliation: SCRI Development Innovations, LLC
name: Johanna Bendell, MD
role: STUDY_CHAIR
References: