Panitumumab in Cetuximab Refractory KRAS Wild-Type Colorectal Cancer

A Single Arm Phase II Trial of Panitumumab in Cetuximab Refractory KRAS Wild-Type Colorectal Cancer

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: panitumumab

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02214
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Panitumumab; Panitumumab administered by a central line infusion on days 1 and 15 of each 4 week cycle.

Drug: panitumumab; Panitumumab is administered intravenously (IV) by an infusion pump through a peripheral line or indwelling catheter using a 0.2 or 0.22-micron in-line filter infusion set-up over 1 hour 15 minutes. The starting panitumumab dose is 6 mg/kg administered every 14 days for as long as patients are on study without evidence of disease progression or demonstrating intolerance to treatment. The total dose may be rounded up or down by no greater than 10 mg. The panitumumab dose will be calculated based on the subject's actual body weight at each visit. Panitumumab will be diluted in a minimum of 100 mL of pyrogen-free 0.9% sodium chloride solution (normal saline solution, supplied by the site). The maximum concentration of the diluted solution to be infused should not exceed 10 mg/mL.; Other Names: Vectibix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate of Single Agent Panitumumab Among Patients With KRAS Wild-type Colorectal Cancer Previously Treated With Cetuximab.	The response rate of single agent panitumumab among patients with KRAS wild-type (Kirsten rat sarcoma viral oncogene homolog) colorectal cancer previously treated with cetuximab. Inclusive of three patients with clinical progression prior to first re-staging CT scans. Response rate evaluated using RECIST (Response Evaluation Criteria In Solid Tumors). Best overall response is recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). RECIST: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD (longest diameter) of target lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression Free Survival (PFS)	The duration of time from start of treatment to time of radiologic disease progression per RECIST or death, or otherwise the date of last tumor assessment. Median PFS was calculated using Kaplan Meier suvival analysis. Progressive disease is defined as having at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	3 years
Median Overall Survival	The duration of time from start of treatment to time of death or otherwise the date of last tumor assessment. Median survival was calculated using Kaplan Meier suvival analysis.	3 years
Disease Control Rate as Defined by RECIST Criteria	Disease Control Rate as defined by RECIST criteria. The number patients achieving stable disease, partial response, or complete response at some point during follow-up.	3 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Dana-Farber Cancer Institute; Beth Israel Deaconess Medical Center; Amgen
• Investigators: Principal Investigator: Aram Hezel, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2009
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: February 10, 2009
• First Submitted That Met QC Criteria: February 10, 2009
• First Posted (ESTIMATE): February 12, 2009

Study Record Updates

• Last Update Posted (ACTUAL): May 16, 2017
• Last Update Submitted That Met QC Criteria: April 10, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: cetuximab; panitumumab; KRAS wild-type
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Panitumumab
• Other Study ID Numbers: 08-287; 20070602 (OTHER: Amgen)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO