Clinical trial NCT01294826: 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
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Swedish Medical Center
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2011-02-14
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Incidence of dose limiting toxicity (DLT)
timeFrame: 1 cycle (1 cycle = 28 days)
Secondary outcomes:
measure: Patient response rate to the AUY922.
timeFrame: After 2 years
measure: Time to tumor progression following treatment with AUY922.
timeFrame: After 2 years
measure: Overall survival of patients treated with AUY922.
timeFrame: After 2 years
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Swedish Medical Center Cancer Institute
state: Washington
Study officials:
affiliation: Swedish Medical Center Cancer Institute
name: Philip Gold, MD
role: PRINCIPAL_INVESTIGATOR
References: