Panitumumab and Bortezomib for Patients With Advanced Colorectal Cancer

Phase 1

Terminated

Conditions: Colorectal Cancer

Interventions: Drug: Panitumumab and bortezomib

Registration Number: NCT01504477

Lead Sponsor: Georgetown University

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 6

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Combination of Panitumumab and Bortezomib	Panitumumab and bortezomib	IV panitumumab and bortezomib

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose	12 months	The maximum tolerated dose of panitumumab (to be used in combination with bortezomib)

Secondary Outcome Measures

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