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

Phase IB With Expansion of Patients at the MTD Study of AUY922 and Cetuximab in Patients With KRAS Wild-Type Metastatic Colorectal Cancer

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.

Study Overview

• Status: Completed
• Conditions: Stage IV Colon Cancer; Stage IV Rectal Cancer; Recurrent Colon Cancer; Recurrent Rectal Cancer; Adenocarcinoma of the Rectum; Adenocarcinoma of the Colon
• Intervention / Treatment: Drug: AUY922; Drug: Cetuximab

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: AUY922 plus Cetuximab

Drug: 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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of dose limiting toxicity (DLT)	1 cycle (1 cycle = 28 days)

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Swedish Medical Center
• Collaborators: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Philip Gold, MD, Swedish Medical Center Cancer Institute

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: February 8, 2011
• First Submitted That Met QC Criteria: February 10, 2011
• First Posted (Estimate): February 14, 2011

Study Record Updates

• Last Update Posted (Estimate): June 8, 2015
• Last Update Submitted That Met QC Criteria: June 4, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Neoplasms; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Cetuximab; Colorectal Neoplasms; Colonic Diseases; Neoplasms by Site; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Rectal Diseases; HSP90 Heat-Shock Proteins; EGFR protein, human
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Recurrence; Adenocarcinoma; Rectal Neoplasms; Colonic Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: CAUY922AUS06T