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

Primary Purpose

Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AUY922
Cetuximab
Sponsored by
Swedish Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Colon Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Swedish Medical Center Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AUY922 plus Cetuximab

Arm Description

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicity (DLT)

Secondary Outcome Measures

Patient response rate to the AUY922.
Time to tumor progression following treatment with AUY922.
Overall survival of patients treated with AUY922.

Full Information

First Posted
February 8, 2011
Last Updated
June 4, 2015
Sponsor
Swedish Medical Center
Collaborators
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01294826
Brief Title
Study of AUY922 and Cetuximab in Patients With KRAS Wild-Type Metastatic Colorectal Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swedish Medical Center
Collaborators
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AUY922 plus Cetuximab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AUY922
Intervention Description
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
Intervention Name(s)
Cetuximab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicity (DLT)
Time Frame
1 cycle (1 cycle = 28 days)
Secondary Outcome Measure Information:
Title
Patient response rate to the AUY922.
Time Frame
After 2 years
Title
Time to tumor progression following treatment with AUY922.
Time Frame
After 2 years
Title
Overall survival of patients treated with AUY922.
Time Frame
After 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philip Gold, MD
Organizational Affiliation
Swedish Medical Center Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Swedish Medical Center Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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