Study of AUY922 and Cetuximab in Patients With KRAS Wild-Type Metastatic Colorectal Cancer

NCT ID: NCT01294826

Last Updated: 2015-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2015-05-31

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.

Conditions

Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer; Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AUY922 plus Cetuximab

Group Type: EXPERIMENTAL

AUY922

Intervention Type: DRUG

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.

Cetuximab

Intervention Type: DRUG

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.

Interventions

AUY922

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.

Intervention Type: DRUG

Cetuximab

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Swedish Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philip Gold, MD

Role: PRINCIPAL_INVESTIGATOR

Swedish Medical Center Cancer Institute

Locations

Swedish Medical Center Cancer Institute

Seattle, Washington, United States

Countries

United States

Other Identifiers

CAUY922AUS06T

Identifier Type: -

Identifier Source: org_study_id