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

Recurrent Rectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01294826
• Other study ID #: CAUY922AUS06T
• Status: Completed
• Phase: Phase 1
• First received: February 8, 2011
• Last updated: June 4, 2015
• Start date: February 2011
• Est. completion date: May 2015

Study information

• Verified date: June 2015
• Source: Swedish Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Colon
• Adenocarcinoma of the Rectum
• Colorectal Neoplasms
• Rectal Neoplasms
• Recurrent Colon Cancer
• Recurrent Rectal Cancer
• Stage IV Colon Cancer
• Stage IV Rectal Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Swedish Medical Center Cancer Institute	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Swedish Medical Center	Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicity (DLT)		1 cycle (1 cycle = 28 days)	Yes
Secondary	Patient response rate to the AUY922.		After 2 years	No
Secondary	Time to tumor progression following treatment with AUY922.		After 2 years	No
Secondary	Overall survival of patients treated with AUY922.		After 2 years	No