Clinical trial NCT00842257: Panitumumab in Cetuximab Refractory KRAS Wild-Type Colorectal Cancer
Official title: A Single Arm Phase II Trial of Panitumumab in Cetuximab Refractory KRAS Wild-Type Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: panitumumab
cetuximab
KRAS wild-type
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Beth Israel Deaconess Medical Center
name: Dana-Farber Cancer Institute
name: Amgen
First posted: 2009-02-12
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 purpose of this research study is to learn whether panitumumab helps treat colorectal cancer in participants who have not responded to treatment with cetuximab. Panitumumab is a human monoclonal antibody. Antibodies are proteins that recognize a foreign substance in the body and then attach themselves to it making it exposed to destruction. Panitumumab attaches itself to a protein on cancer cells called "epidermal growth factor receptor" or EGFR. EGFR helps cancer cells to grow, and blocking EGFR helps prevent cancer cells from growing.

Detailed description: * Panitumumab will be given to the participants through a central line. A central line is a long, thin tube (catheter) that is inserted through the skin into a large vein in the chest. This is placed by a radiologist or surgeon.
* Panitumumab will be given in 4-week cycles. Panitumumab infusions will be given on days 1 and 15 of each cycle (every 2 weeks).
* The following procedures will be performed on days 1 and 15 of each cycle, before each infusion: physical exam; questions about any symptoms or side effects; performance status; routine blood tests and CT or MRI (every 2 cycles).
* Participants can continue to receive panitumumab until their disease gets worse or they experience unacceptable side effects.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma and measurable disease by RECIST criteria on CT or MRI
* Treated with cetuximab as part of their last treatment regimen for at least 4 weeks and must have been taken off cetuximab therapy for disease progression. Patients may or may not have been treated with 5-FU (5-Fluorouracil), oxaliplatin, irinotecan and bevacizumab. There is no maximal number of pre-existing treatment regimens. At least 2 weeks must have elapsed between previous anticancer therapy and the start of treatment on protocol, AND resolution of any skin rash related to prior treatment with epidermal growth factor receptor inhibitor
* ECOG (Eastern Cooperative Oncology Group) Performance Status 0, 1 or 2
* Life expectancy of greater than 3 months
* Normal organ, metabolic, and marrow function as defined in the protocol
* A wild-type tumor K-RAS gene (Kirsten rat sarcoma viral oncogene homolog) as determined by sanger sequencing of exon 2 from tumor DNA
* 18 years of age or older

Exclusion Criteria:

* History of untreated and or progression central nervous system metastases
* History of another primary cancer except: curatively treated in situ cervical cancer or breast; curatively resected non-melanoma skin cancer; other primary solid tumor curatively treated with no known active disease present and no treatment administered for 3 years or more prior to enrollment
* Intolerance to cetuximab leading to drug discontinuation due to rash, GI toxicity, or other grade 3 or 4 toxicities
* Radiotherapy \< 14 days prior to enrollment
* Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies \< 14 days before enrollment
* Subjects requiring chronic use of immunosuppressive agents
* Any investigational agent or therapy 30 days prior to enrollment
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with any study requirements
* History of interstitial lung disease
* Women who test positive for serum or urine pregnancy test or who are breast feeding

Primary outcomes:
measure: Response Rate of Single Agent Panitumumab Among Patients With KRAS Wild-type Colorectal Cancer Previously Treated With Cetuximab.
timeFrame: 3 years
Secondary outcomes:
measure: Median Progression Free Survival (PFS)
timeFrame: 3 years
measure: Median Overall Survival
timeFrame: 3 years
measure: Disease Control Rate as Defined by RECIST Criteria
timeFrame: 3 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Aram Hezel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wadlow RC, Hezel AF, Abrams TA, Blaszkowsky LS, Fuchs CS, Kulke MH, Kwak EL, Meyerhardt JA, Ryan DP, Szymonifka J, Wolpin BM, Zhu AX, Clark JW. Panitumumab in patients with KRAS wild-type colorectal cancer after progression on cetuximab. Oncologist. 2012;17(1):14. doi: 10.1634/theoncologist.2011-0452. Epub 2011 Dec 30.