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Panitumumab in Cetuximab Refractory KRAS Wild-Type Colorectal Cancer

Primary Purpose

Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
panitumumab
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring panitumumab, cetuximab, KRAS wild-type

Eligibility Criteria

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

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

Sites / Locations

  • Beth Israel Deaconess Medical Center
  • Dana-Farber Cancer Institute
  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Panitumumab

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
February 10, 2009
Last Updated
April 10, 2017
Sponsor
Massachusetts General Hospital
Collaborators
Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute, Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT00842257
Brief Title
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

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
May 2009 (Actual)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute, Amgen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
panitumumab, cetuximab, KRAS wild-type

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Panitumumab
Arm Type
Experimental
Arm Description
Panitumumab administered by a central line infusion on days 1 and 15 of each 4 week cycle.
Intervention Type
Drug
Intervention Name(s)
panitumumab
Other Intervention Name(s)
Vectibix
Intervention Description
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.
Primary Outcome Measure Information:
Title
Response Rate of Single Agent Panitumumab Among Patients With KRAS Wild-type Colorectal Cancer Previously Treated With Cetuximab.
Description
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
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Median Progression Free Survival (PFS)
Description
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.
Time Frame
3 years
Title
Median Overall Survival
Description
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.
Time Frame
3 years
Title
Disease Control Rate as Defined by RECIST Criteria
Description
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.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aram Hezel, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02214
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
22210091
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.
Results Reference
derived

Learn more about this trial

Panitumumab in Cetuximab Refractory KRAS Wild-Type Colorectal Cancer

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