Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer
Conditions
Keywords
Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases, Cetuximab, HSP90 Heat-Shock Proteins, EGFR protein, human
Brief summary
The study will determine the maximum tolerated dose (MTD) of AUY922 given in combination with cetuximab in previously treated patients with KRAS wild-type metastatic colorectal cancer.
Interventions
DRUGAUY922
Weekly intravenous infusion on Day 1, 8, 15 and 22 of each 28 day cycle until unacceptable toxicity develops or disease progression. A minimum of 3 patients will be enrolled into each cohort. The anticipated dose escalation sequence of AUY922 is 40, 55, and 70 mg/m2 will be used.
DRUGCetuximab
Cetuximab will be administered after each AUY922 infusion, intravenously on Day 1, 8, 15 and 22 of each 28 day cycle until unacceptable toxicity develops or disease progression.
Sponsors
Novartis Pharmaceuticals
Swedish Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed colorectal cancer * KRAS wild type metastatic colorectal cancer * Progression of disease on at least 2 prior therapy to have included 5FU, or oxaliplatin or bevacizumab or irinotecan * Prior treatment with cetuximab is allowed (full dose tolerated), provided that the patient never required a dose reduction due to toxicities * Must have at least one measurable lesion * Must be 18 years of age or older * ECOG performance status 0-1 * Life expectancy must be greater than 12 weeks * For women of childbearing potential, a negative pregnancy blood test must be obtained less than 3 days prior to the first AUY922 infusion
Exclusion criteria
* Colorectal cancer with a KRAS mutation or in which the KRAS genotype status is unknown * Metastasis to the CNS * Prior treatment with any Hsp90 inhibitor compounds * Patients who received systemic anti-cancer treatment prior to the first dose of AUY922 within the following time frames: * Radiotherapy, conventional chemotherapy: within 2 weeks * Palliative radiotherapy: within 2 weeks * Nitrosoureas, monoclonal antibodies, such as trastuzumab and mitomycin: within 6 weeks * Any continuous-dosing (i.e. daily dosing, every-other-day dosing, Monday-Wednesday-Friday dosing, weekly etc.) of systemic anti-cancer treatment for which the recover period is not known, or investigational drugs (i.e. targeted agents) within a duration of ≤ 5 half lives of the agent and their active metabolites (if any) * Treatment of therapeutic doses of coumadin-type anticoagulants. \[Maximum daily dose of 2mg, for line patency permitted\] * Known sensitivity to cetuximab * Unresolved ≥ grade 1 diarrhea * Malignant ascites that require invasive treatment * Concurrent medications that are substrates, inhibitors or inducers of CYP3A4, CYP2C8, CYP2C9 and CYP2C19 and cannot be switched or discontinued or switched to an alternative drug prior to commencing AUY922 dosing need special consideration on a case by case basis * Major surgery ≤ 2 weeks prior to randomization or who have not recovered from such therapy * Impaired cardiac function
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose limiting toxicity (DLT) | 1 cycle (1 cycle = 28 days) |
Secondary
| Measure | Time frame |
|---|---|
| Patient response rate to the AUY922. | After 2 years |
| Time to tumor progression following treatment with AUY922. | After 2 years |
| Overall survival of patients treated with AUY922. | After 2 years |
Countries
United States
Outcome results
None listed