Panitumumab and Bortezomib for Patients With Advanced Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
Panitumumab plus bortezomib for colon cancer

Detailed Description
-----------------
This study is for patients with colon cancer that cannot be fully removed by surgery and has come back after or not responded to standard chemotherapy treatment. Subjects will be enrolled to either the first part of the study (Phase I) or the second part of the study (Phase II). Phase I will be completed before Phase II will start. The purpose of the Phase I part is to find the highest dose of bortezomib that can be given with panitumumab without causing severe side effects. The purpose of the Phase II part is to test the effects the two drugs have on subjects with colorectal cancer. Panitumumab is a drug that targets a protein important for the growth of cancer cells known as EGFR. By blocking the activity of the protein, panitumumab can block cancer cell growth and even lead to their death. Panitumumab is given intravenously once every two weeks. Panitumumab is approved by the FDA for patients with colorectal cancer. Bortezomib is a drug that targets a part of the cancer cell known as the proteosome. By inhibiting the proteosome, bortezomib can inhibit cancer cell growth and even lead to their death. Bortezomib is given intravenously, once a week, 3 out of every 4 weeks. Bortezomib is not FDA approved for the treatment of colorectal cancer. As part of this study the investigators will be taking biopsies of patients' tumors before any treatment, after starting with the panitumumab alone, and after receiving both the panitumumab and bortezomib. The investigators want to investigate what markers inside tumors may relate to how well these two medications work. These biopsies are required as part of the study.

Official Title
-----------------
A Phase I/II Clinical Trial of the Anti-EGFR Monoclonal Antibody, Panitumumab, and the Proteosomal Inhibitor, Bortezomib, in Patients With Advanced, Refractory KRAS Wild-Type Colorectal Cancer

Conditions
-----------------
Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: Panitumumab and bortezomib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically proven colorectal cancer with measurable or evaluable disease KRAS wild-type colorectal cancer Progression on, or intolerance of, or ineligibility for all standard therapies Progression on prior anti-EGFR therapy Lesion that is amenable to biopsy ECOG performance status 0-2 LVEF >/= institutional normal Corrected QT interval less then 500 milliseconds by EKG Grade 2 or less peripheral neuropathy Adequate hepatic, bone marrow, and renal function Partial thromboplastin time must be </= 1.5 x upper limit of institution's normal range and INR < 1.5. Subjects on anticoagulants will be permitted to enroll as long as the INR is in the acceptable therapeutic range as determined by the investigator. Subjects with no brain metastases or a history of previously treated brain metastases who have been treated by surgery or stereotactic radiosurgery at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of active intracranial disease and have not had treatment with steroids within 1 week of study enrollment. Life expectancy > 12 weeks Subject is capable of understanding and complying with parameters of the protocol and able to sign and date the informed consent form. Exclusion Criteria: CNS metastases which do not meet the criteria above Prior cancer chemotherapy, radiation therapy, or any investigational agent within three weeks before starting therapy Active severe infection or known chronic infection with HIV or hepatitis B virus Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 months Peripheral neuropathy >/= Grade 2 at baseline or peripheral neuropathy >/= Grade 1 with neuropathic pain Life-threatening visceral disease or other severe concurrent disease Female subject is pregnant or lactating Diagnosed or treated for another malignancy within 3 years of enrollment with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy Patient has hypersensitivity to bortezomib, boron, or mannitol Clinically significant and uncontrolled major medical condition(s)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination of Panitumumab and Bortezomib<br>IV panitumumab and bortezomib | Drug: Panitumumab and bortezomib<br>* Panitumumab 6 mg/kg IV over 60 minutes on Day -14 (first cycle only), then Day 1 and 15 of each 28-day cycle. Bortezomib will be administered in escalating doses until the maximum tolerated dose is determined and then at the maximum tolerated dose as an IV bolus injection over 3-5 seconds on Day 1, 8, and 15 of each 28-day cycle.<br>* Other names: Vectibix;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose | The maximum tolerated dose of bortezomib (to be used in combination with panitumumab) | 12 months | 
| Maximum Tolerated Dose | The maximum tolerated dose of panitumumab (to be used in combination with bortezomib) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Patients With Disease Control | Stable disease after 2 cycles, partial response or complete response as determined by RECIST v1.0 | 16 weeks | 
| Percent of of Patients With a Complete or Partial Response | Partial response plus complete response as per RECIST v1.0 | 16 weeks | 
| Duration of Disease Control | Time from study registration until progressive disease | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
colorectal cancer, relapsed, refractory, Kras wild type