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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Swedish Medical Center
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Swedish Medical Center
ClinicalTrials.gov Identifier:
NCT01294826
First received: February 8, 2011
Last updated: July 23, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage IV Colon Cancer
Stage IV Rectal Cancer
Adenocarcinoma of the Colon
Adenocarcinoma of the Rectum
Drug: AUY922
Drug: Cetuximab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase IB With Expansion of Patients at the MTD Study of AUY922 and Cetuximab in Patients With KRAS Wild-Type Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Swedish Medical Center:

Primary Outcome Measures:
  • Incidence of dose limiting toxicity (DLT) [ Time Frame: 1 cycle (1 cycle = 28 days) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Patient response rate to the AUY922. [ Time Frame: After 2 years ] [ Designated as safety issue: No ]
  • Time to tumor progression following treatment with AUY922. [ Time Frame: After 2 years ] [ Designated as safety issue: No ]
  • Overall survival of patients treated with AUY922. [ Time Frame: After 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: February 2011
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01294826

Contacts
Contact: Barry Boatman, RN, MA, OCN (206) 215-3086 CancerResearch@Swedish.org

Locations
United States, Washington
Swedish Medical Center Cancer Institute Recruiting
Seattle, Washington, United States, 98104
Contact: Barry Boatman, RN, MA, OCN    206-215-3086    CancerResearch@Swedish.org   
Contact: Barry         
Principal Investigator: Philip Gold, MD         
Sponsors and Collaborators
Swedish Medical Center
Novartis Pharmaceuticals
Investigators
Principal Investigator: Philip Gold, MD Swedish Medical Center Cancer Institute
  More Information

No publications provided

Responsible Party: Swedish Medical Center
ClinicalTrials.gov Identifier: NCT01294826     History of Changes
Other Study ID Numbers: CAUY922AUS06T
Study First Received: February 8, 2011
Last Updated: July 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Swedish Medical Center:
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

Additional relevant MeSH terms:
Adenocarcinoma
Colonic Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014