A Study of the Hsp90 Inhibitor AUY922 Plus Capecitabine for the Treatment of Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01226732
First received: October 18, 2010
Last updated: June 27, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Metastatic or Unresectable Solid Tumor Malignancy
Drug: Capecitabine
Drug: Hsp90 Inhibitor AUY 922
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of the Hsp90 Inhibitor AUY922 Plus Capecitabine for the Treatment of Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Dose determination [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    To determine the maximum tolerated dose (MTD) of AUY922 plus capecitabine in patients with advanced solid tumors.


Secondary Outcome Measures:
  • Safety [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    To evaluate the drug related toxicities associated with different doses of the drugs used in this regimen.

  • pharmacokinetic (PK) profile [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    To evaluate the drug metabolism of AUY922 by patients who are also receiving capecitabine.

  • Efficacy [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    To preliminarily assess anti tumor efficacy of this regimen (response rate [RR], progression-free survival [PFS]).


Enrollment: 23
Study Start Date: November 2010
Study Completion Date: June 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Hsp90 Inhibitor AUY922 plus Capecitabine for the Treatment of Patients with Advanced Solid Tumors
Drug: Capecitabine
Taken orally twice daily on Days 1 through 14 of 21 day cycle.
Other Name: Xeloda
Drug: Hsp90 Inhibitor AUY 922
IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle

  Eligibility

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

Inclusion Criteria:

  1. Histologically confirmed metastatic or unresectable solid tumor malignancy that is incurable and for which capecitabine is clinically appropriate.
  2. 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.
  3. Eastern Collaborative Oncology Group (ECOG) performance status 0 to 1 (see Appendix A).
  4. Life expectancy of ≥3 months.
  5. 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).
  6. Normal bone marrow function defined as:

    • Absolute neutrophil count (ANC) ≥1500/μL
    • Hemoglobin (Hgb) ≥9 g/dL
    • Platelets ≥100,000/μL
  7. 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
  8. Renal function defined as:

    • Serum creatinine ≤1.5 x ULN or 24-hour creatinine clearance ≥40 mL/min

  9. Normal electrolytes defined as:

    • Phosphorous ≥ LLN
    • Magnesium ≥ LLN
  10. 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.
  11. Must be ≥18 years of age.
  12. Patients must be accessible for treatment and follow-up.
  13. Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.

Exclusion Criteria:

  1. 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.
  2. Treatment with therapeutic doses of coumarin-type anticoagulants (maximum daily dose of 1 mg allowed for port line patency permitted).
  3. 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
  4. 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).
  5. Patients with known diagnosis of human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.
  6. 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.
  7. Women who are pregnant (positive pregnancy test) or lactating.
  8. 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.
  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: NCT01226732

Locations
United States, Florida
Florida Cancer Specialists
Ft. Myers, Florida, United States, 33916
United States, Oklahoma
Oklahoma University
Oklahoma City, Oklahoma, United States, 71304
United States, Tennessee
Tennessee Oncology
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
SCRI Development Innovations, LLC
Novartis Pharmaceuticals
Investigators
Study Chair: Johanna C Bendell, MD SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01226732     History of Changes
Other Study ID Numbers: SCRI GI 143
Study First Received: October 18, 2010
Last Updated: June 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Solid tumor
Capecitabine
Hsp90 inhibitor AUY922

Additional relevant MeSH terms:
Neoplasms
Capecitabine
Fluorouracil
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 23, 2014