- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01226732
A Study of the Hsp90 Inhibitor AUY922 Plus Capecitabine for the Treatment of Patients With Advanced Solid Tumors
February 15, 2022 updated by: SCRI Development Innovations, LLC
A Phase I Study of the Hsp90 Inhibitor AUY922 Plus Capecitabine for the Treatment of Patients With Advanced Solid Tumors
The investigators propose this Phase I trial of the combination of AUY922 and capecitabine to determine the maximum tolerated dose (MTD) in patients with advanced solid tumors.
This combination treatment has potential applicability in tumor types where capecitabine or fluorouracil is a treatment option, including colorectal and breast cancer.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
23
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Florida
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Fort Myers, Florida, United States, 33916
- Florida Cancer Specialists
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Oklahoma
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Oklahoma City, Oklahoma, United States, 71304
- Oklahoma University
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Tennessee
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Nashville, Tennessee, United States, 37203
- Tennessee Oncology
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Histologically confirmed metastatic or unresectable solid tumor malignancy that is incurable and for which capecitabine is clinically appropriate.
- Patient must be ≥4 weeks from administration of last dose of cancer therapy (including radiation therapy, biologic therapy, hormonal therapy or chemotherapy). Patients who received a small molecule targeted therapy as part of their first line treatment regimen must be ≥4 weeks or ≥5 half lives from administration of last dose whichever is shorter. The patient must have recovered from or come to a new chronic stable baseline from all treatment-related toxicities.
- Eastern Collaborative Oncology Group (ECOG) performance status 0 to 1 (see Appendix A).
- Life expectancy of ≥3 months.
- At least one unidimensional measurable lesion definable by MRI or CT scan. Disease must be measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria (see Section 9).
Normal bone marrow function defined as:
- Absolute neutrophil count (ANC) ≥1500/μL
- Hemoglobin (Hgb) ≥9 g/dL
- Platelets ≥100,000/μL
Adequate hepatic function defined as:
- AST or ALT and alkaline phosphatase (ALP) must be ≤3 x ULN, or ≤5 x ULN in patients with liver metastases
- Total bilirubin ≤1.5 x the institutional ULN
Renal function defined as:
• Serum creatinine ≤1.5 x ULN or 24-hour creatinine clearance ≥40 mL/min
Normal electrolytes defined as:
- Phosphorous ≥ LLN
- Magnesium ≥ LLN
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential must use effective birth control measures during treatment and during the 6 months following completion of study treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
- Must be ≥18 years of age.
- Patients must be accessible for treatment and follow-up.
- Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.
Exclusion Criteria:
- Untreated CNS metastases. Patients with treated CNS metastases may be enrolled, provided the patient is asymptomatic, and the patient does not require antiepileptic drugs or steroids as treatment for the CNS metastases.
- Treatment with therapeutic doses of coumarin-type anticoagulants (maximum daily dose of 1 mg allowed for port line patency permitted).
Impaired cardiac function with any one of the following:
- History (or family history) of long QT syndrome
- Mean QTc ≥450 msec on baseline ECG
- History of clinically manifested ischemic heart disease (i.e. myocardial infarction and/or unstable angina) ≤6 months prior to study start
- History of heart failure or 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 (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB). ST segment elevation or depression > 1mm, or 2nd (Mobitz II), or 3rd degree AV block.
- History or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes
- Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
- Clinically significant resting bradycardia (< 50 beats per minute)
- Patients who are 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 (see Appendix D).
- Obligate use of a cardiac pacemaker
- Impairment of gastrointestinal function or gastrointestinal disease that in the opinion of the Investigator may significantly alter the absorption of study drugs (e.g., Crohn's disease, ulcerative disease, uncontrolled vomiting, diarrhea, or malabsorption syndrome).
- Patients with known diagnosis of human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.
- 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.
- Women who are pregnant (positive pregnancy test) or lactating.
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dose Level 1
Hsp90 Inhibitor AUY922: 22mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles
|
Taken orally twice daily on Days 1 through 14 of 21 day cycle.
Other Names:
IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle
|
Experimental: Dose Level 2
Hsp90 Inhibitor AUY922: 28mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles
|
Taken orally twice daily on Days 1 through 14 of 21 day cycle.
Other Names:
IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle
|
Experimental: Dose Level 3
Hsp90 Inhibitor AUY922: 40mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles
|
Taken orally twice daily on Days 1 through 14 of 21 day cycle.
Other Names:
IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle
|
Experimental: Dose Level 4
Hsp90 Inhibitor AUY922: 55mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles
|
Taken orally twice daily on Days 1 through 14 of 21 day cycle.
Other Names:
IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle
|
Experimental: Dose Level 5
Hsp90 Inhibitor AUY922: 70mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles
|
Taken orally twice daily on Days 1 through 14 of 21 day cycle.
Other Names:
IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle
|
Experimental: Dose Level 6
Hsp90 Inhibitor AUY922: 70mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1250mg/m2 PO BID d 1-14 of 21-day cycles
|
Taken orally twice daily on Days 1 through 14 of 21 day cycle.
Other Names:
IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose Determination
Time Frame: 18 months
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To determine the maximum tolerated dose (MTD) of AUY922 plus capecitabine in patients with advanced solid tumors.
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18 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Drug Related Toxicities
Time Frame: 18 months
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To evaluate the drug related toxicities associated with different doses of the drugs used in this regimen.
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18 months
|
Preliminary Efficacy Assessment: Response Rate (RR)
Time Frame: 18 months
|
Response Rate (RR) is defined as the total number of patients with Complete Response (CR) or Partial Response (PR) as defined in RECIST v2.
CR is defined as the dissappearance of all target lesions, disappearance of all non-target lesions and normalization of tumor markers.
PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
|
18 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Study Chair: Johanna C Bendell, MD, SCRI Development Innovations, LLC
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2010
Primary Completion (Actual)
July 1, 2013
Study Completion (Actual)
June 1, 2014
Study Registration Dates
First Submitted
October 18, 2010
First Submitted That Met QC Criteria
October 20, 2010
First Posted (Estimate)
October 22, 2010
Study Record Updates
Last Update Posted (Actual)
March 8, 2022
Last Update Submitted That Met QC Criteria
February 15, 2022
Last Verified
February 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SCRI GI 143
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.
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