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

Sponsor
SCRI Development Innovations, LLC (Other)
Overall Status
Completed
CT.gov ID
NCT01226732
Collaborator
Novartis Pharmaceuticals (Industry)
23
Enrollment
3
Locations
6
Arms
43
Duration (Months)
7.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
23 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (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
Study Start Date :
Nov 1, 2010
Actual Primary Completion Date :
Jul 1, 2013
Actual Study Completion Date :
Jun 1, 2014

Arms and Interventions

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

Drug: Capecitabine
Taken orally twice daily on Days 1 through 14 of 21 day cycle.
Other Names:
  • Xeloda

    • Drug: Hsp90 Inhibitor AUY 922
    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

    Drug: Capecitabine
    Taken orally twice daily on Days 1 through 14 of 21 day cycle.
    Other Names:
  • Xeloda

    • Drug: Hsp90 Inhibitor AUY 922
    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

    Drug: Capecitabine
    Taken orally twice daily on Days 1 through 14 of 21 day cycle.
    Other Names:
  • Xeloda

    • Drug: Hsp90 Inhibitor AUY 922
    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

    Drug: Capecitabine
    Taken orally twice daily on Days 1 through 14 of 21 day cycle.
    Other Names:
  • Xeloda

    • Drug: Hsp90 Inhibitor AUY 922
    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

    Drug: Capecitabine
    Taken orally twice daily on Days 1 through 14 of 21 day cycle.
    Other Names:
  • Xeloda

    • Drug: Hsp90 Inhibitor AUY 922
    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

    Drug: Capecitabine
    Taken orally twice daily on Days 1 through 14 of 21 day cycle.
    Other Names:
  • Xeloda

    • Drug: Hsp90 Inhibitor AUY 922
    IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle

    Outcome Measures

    Primary Outcome Measures

    1. Dose Determination [18 months]

      To determine the maximum tolerated dose (MTD) of AUY922 plus capecitabine in patients with advanced solid tumors.

    Secondary Outcome Measures

    1. Drug Related Toxicities [18 months]

      To evaluate the drug related toxicities associated with different doses of the drugs used in this regimen.

    2. Preliminary Efficacy Assessment: Response Rate (RR) [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. 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

    1. Renal function defined as:

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

    1. Normal electrolytes defined as:

    • Phosphorous ≥ LLN

    • Magnesium ≥ LLN

    1. 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.

    2. Must be ≥18 years of age.

    3. Patients must be accessible for treatment and follow-up.

    4. 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

    1. 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).

    2. Patients with known diagnosis of human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.

    3. 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.

    4. Women who are pregnant (positive pregnancy test) or lactating.

    5. 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

    Locations

    Site City State Country Postal Code
    1 Florida Cancer Specialists Fort Myers Florida United States 33916
    2 Oklahoma University Oklahoma City Oklahoma United States 71304
    3 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    SCRI Development Innovations, LLC
    ClinicalTrials.gov Identifier:
    NCT01226732
    Other Study ID Numbers:
    • SCRI GI 143
    First Posted:
    Oct 22, 2010
    Last Update Posted:
    Mar 8, 2022
    Last Verified:
    Feb 1, 2022
    Keywords provided by SCRI Development Innovations, LLC
    Solid tumor
    Capecitabine
    Hsp90 inhibitor AUY922
    Additional relevant MeSH terms:
    Neoplasms
    Capecitabine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 Dose Level 6
    Arm/Group Description 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle
    Period Title: Overall Study
    STARTED 3 3 3 5 3 6
    COMPLETED 0 0 0 0 0 0
    NOT COMPLETED 3 3 3 5 3 6

    Baseline Characteristics

    Arm/Group Title Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 Dose Level 6 Total
    Arm/Group Description 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle Total of all reporting groups
    Overall Participants 3 3 3 5 3 6 23
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    59
    51
    64
    60
    58
    65.5
    60
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    1
    33.3%
    2
    40%
    1
    33.3%
    3
    50%
    7
    30.4%
    Male
    3
    100%
    3
    100%
    2
    66.7%
    3
    60%
    2
    66.7%
    3
    50%
    16
    69.6%
    Region of Enrollment (participants) [Number]
    United States
    3
    100%
    3
    100%
    3
    100%
    5
    100%
    3
    100%
    6
    100%
    23
    100%

    Outcome Measures

    1. Primary Outcome
    Title Dose Determination
    Description To determine the maximum tolerated dose (MTD) of AUY922 plus capecitabine in patients with advanced solid tumors.
    Time Frame 18 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title All Patients
    Arm/Group Description The Maximum Tolerated Dose (MTD) is determined for all patients
    Measure Participants 23
    AUY922 dose
    70
    Capecitabine dose
    1250
    2. Secondary Outcome
    Title Drug Related Toxicities
    Description To evaluate the drug related toxicities associated with different doses of the drugs used in this regimen.
    Time Frame 18 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 Dose Level 6
    Arm/Group Description 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle
    Measure Participants 3 3 3 5 3 6
    Vision changes
    0
    0%
    0
    0%
    1
    33.3%
    3
    60%
    3
    100%
    6
    100%
    Diarrhea
    1
    33.3%
    1
    33.3%
    2
    66.7%
    3
    60%
    3
    100%
    4
    66.7%
    Fatigue
    3
    100%
    0
    0%
    1
    33.3%
    1
    20%
    1
    33.3%
    4
    66.7%
    Nausea
    2
    66.7%
    2
    66.7%
    1
    33.3%
    3
    60%
    1
    33.3%
    0
    0%
    Hand-foot syndrome
    1
    33.3%
    0
    0%
    0
    0%
    2
    40%
    1
    33.3%
    5
    83.3%
    Anorexia
    2
    66.7%
    0
    0%
    0
    0%
    3
    60%
    1
    33.3%
    2
    33.3%
    Vomiting
    2
    66.7%
    0
    0%
    1
    33.3%
    2
    40%
    2
    66.7%
    0
    0%
    3. Secondary Outcome
    Title Preliminary Efficacy Assessment: Response Rate (RR)
    Description 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.
    Time Frame 18 months

    Outcome Measure Data

    Analysis Population Description
    Includes all patients evaluable for response. 4 patients were not evaluable: dose level 2 (1 pt), dose level 4 (2 pts), dose level 6 (1 pt).
    Arm/Group Title Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 Dose Level 6
    Arm/Group Description 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 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 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 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 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 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
    Measure Participants 3 2 3 3 3 5
    Number [participants]
    1
    33.3%
    0
    0%
    0
    0%
    2
    40%
    1
    33.3%
    0
    0%

    Adverse Events

    Time Frame 18 months
    Adverse Event Reporting Description
    Arm/Group Title Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 Dose Level 6
    Arm/Group Description 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle 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 Capecitabine: Taken orally twice daily on Days 1 through 14 of 21 day cycle. Hsp90 Inhibitor AUY 922: IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle
    All Cause Mortality
    Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 Dose Level 6
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 Dose Level 6
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/5 (20%) 0/3 (0%) 0/6 (0%)
    Gastrointestinal disorders
    Rectal hemorrhage 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/5 (20%) 0/3 (0%) 0/6 (0%)
    General disorders
    General disorders and administration site conditions - Other, failure to thrive 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 0/3 (0%) 0/6 (0%)
    Metabolism and nutrition disorders
    Dehydration 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 0/3 (0%) 0/6 (0%)
    Skin and subcutaneous tissue disorders
    Palmar-plantar erythrodysesthesia syndrome 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 0/3 (0%) 0/6 (0%)
    Other (Not Including Serious) Adverse Events
    Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 Dose Level 6
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 3/3 (100%) 3/3 (100%) 5/5 (100%) 3/3 (100%) 6/6 (100%)
    Blood and lymphatic system disorders
    Anemia 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 0/5 (0%) 2/3 (66.7%) 0/6 (0%)
    Eye disorders
    Eye disorders - Other, vision changes 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/5 (20%) 2/3 (66.7%) 2/6 (33.3%)
    Floaters 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/5 (20%) 2/3 (66.7%) 1/6 (16.7%)
    Conjunctivitis 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 1/3 (33.3%) 2/6 (33.3%)
    Dry eye 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/5 (0%) 0/3 (0%) 2/6 (33.3%)
    Flashing lights 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 1/3 (33.3%) 2/6 (33.3%)
    Blurred vision 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/5 (20%) 0/3 (0%) 1/6 (16.7%)
    Eye disorders - Other, color differentiation difficulties 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 0/3 (0%) 2/6 (33.3%)
    Gastrointestinal disorders
    Diarrhea 1/3 (33.3%) 1/3 (33.3%) 2/3 (66.7%) 4/5 (80%) 2/3 (66.7%) 5/6 (83.3%)
    Nausea 2/3 (66.7%) 2/3 (66.7%) 1/3 (33.3%) 5/5 (100%) 2/3 (66.7%) 2/6 (33.3%)
    Vomiting 2/3 (66.7%) 1/3 (33.3%) 1/3 (33.3%) 2/5 (40%) 1/3 (33.3%) 2/6 (33.3%)
    Mucositis 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/5 (20%) 2/3 (66.7%) 3/6 (50%)
    Abdominal pain 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 1/3 (33.3%) 3/6 (50%)
    Constipation 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 1/3 (33.3%) 2/6 (33.3%)
    Dry mouth 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/5 (20%) 0/3 (0%) 1/6 (16.7%)
    Rectal hemorrhage 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/5 (20%) 0/3 (0%) 1/6 (16.7%)
    General disorders
    Fatigue 3/3 (100%) 0/3 (0%) 1/3 (33.3%) 3/5 (60%) 1/3 (33.3%) 4/6 (66.7%)
    Edema limbs 2/3 (66.7%) 0/3 (0%) 0/3 (0%) 1/5 (20%) 0/3 (0%) 1/6 (16.7%)
    Non-cardiac chest pain 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/5 (0%) 0/3 (0%) 1/6 (16.7%)
    Injury, poisoning and procedural complications
    Fall 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 0/3 (0%) 2/6 (33.3%)
    Investigations
    Weight loss 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 1/3 (33.3%) 2/6 (33.3%)
    Aspartate aminotransferase increased 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/5 (0%) 1/3 (33.3%) 1/6 (16.7%)
    Blood bilirubin increased 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/5 (0%) 1/3 (33.3%) 1/6 (16.7%)
    Alanine aminotransferase increased 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 1/3 (33.3%) 1/6 (16.7%)
    Platelet count decreased 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 0/3 (0%) 2/6 (33.3%)
    Metabolism and nutrition disorders
    Anorexia 2/3 (66.7%) 0/3 (0%) 0/3 (0%) 4/5 (80%) 1/3 (33.3%) 2/6 (33.3%)
    Hyperglycemia 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/5 (0%) 1/3 (33.3%) 3/6 (50%)
    Dehydration 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 0/3 (0%) 2/6 (33.3%)
    Hyperuricemia 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/5 (0%) 0/3 (0%) 2/6 (33.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/5 (20%) 1/3 (33.3%) 1/6 (16.7%)
    Myalgia 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 2/5 (40%) 0/3 (0%) 1/6 (16.7%)
    Back pain 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 1/3 (33.3%) 2/6 (33.3%)
    Flank pain 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/5 (0%) 0/3 (0%) 1/6 (16.7%)
    Pain in extremity 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/5 (20%) 0/3 (0%) 0/6 (0%)
    Nervous system disorders
    Peripheral sensory neuropathy 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 2/5 (40%) 0/3 (0%) 1/6 (16.7%)
    Headache 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/5 (40%) 0/3 (0%) 1/6 (16.7%)
    Dizziness 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 1/3 (33.3%) 1/6 (16.7%)
    Respiratory, thoracic and mediastinal disorders
    Cough 1/3 (33.3%) 0/3 (0%) 2/3 (66.7%) 1/5 (20%) 0/3 (0%) 0/6 (0%)
    Skin and subcutaneous tissue disorders
    Palmar-plantar erythrodysesthesia syndrome 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 2/5 (40%) 1/3 (33.3%) 5/6 (83.3%)
    Rash 2/3 (66.7%) 0/3 (0%) 1/3 (33.3%) 1/5 (20%) 1/3 (33.3%) 2/6 (33.3%)
    Skin and subcutaneous tissue disorders - Other, skin changes 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/5 (40%) 0/3 (0%) 1/6 (16.7%)
    Vascular disorders
    Hypertension 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/5 (0%) 1/3 (33.3%) 0/6 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The sponsor can review/embargo results communications prior to public release for a period that is >60 but =180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites

    Results Point of Contact

    Name/Title John D Hainsworth, MD
    Organization Sarah Cannon Research Institute
    Phone 1-877-691-7274
    Email asksarah@scresearch.net
    Responsible Party:
    SCRI Development Innovations, LLC
    ClinicalTrials.gov Identifier:
    NCT01226732
    Other Study ID Numbers:
    • SCRI GI 143
    First Posted:
    Oct 22, 2010
    Last Update Posted:
    Mar 8, 2022
    Last Verified:
    Feb 1, 2022