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

NCT01294826 | Completed Phase 1

• 1 other identifier: CAUY922AUS06T
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (1)

• Incidence of dose limiting toxicity (DLT)

  1 cycle (1 cycle = 28 days)

Secondary Outcomes (3)

• 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

Study Arms (1)

AUY922 plus Cetuximab

EXPERIMENTAL

Drug: AUY922; Drug: Cetuximab

Interventions

AUY922 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.

AUY922 plus Cetuximab

Cetuximab 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.

AUY922 plus Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Swedish Medical Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Swedish Medical Center Cancer Institute

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Interventions

5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide; Cetuximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Philip Gold, MD

  Swedish Medical Center Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2011
• First Posted: February 14, 2011
• Study Start: February 1, 2011
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: June 8, 2015

Record last verified: 2015-06

Locations

US (1)