Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Antimetabolites

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

Taken orally twice daily on Days 1 through 14 of 21 day cycle.

IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle

Hsp90 Inhibitor AUY 922

Johanna C Bendell, MD

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.

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

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

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

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

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.

Novartis Pharmaceuticals

SCRI Development Innovations, LLC

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

Dose Level 1

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

Dose Level 2

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

Dose Level 3

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

Dose Level 4

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

Dose Level 5

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

Dose Level 6

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

John D Hainsworth, MD

AUY922 dose

Capecitabine dose

The Maximum Tolerated Dose (MTD) is determined for all patients

All Patients

Dose Determination

Vision changes

Diarrhea

Fatigue

Nausea

Hand-foot syndrome

Anorexia

Vomiting

Drug Related Toxicities

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).

Spots Global Cancer Trial Database for metastatic or unresectable solid tumor malignancy