Panitumumab and Bortezomib for Patients With Advanced Colorectal Cancer

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

Panitumumab plus bortezomib for colon cancer

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Panitumumab and bortezomib

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown Lombardi Comprehensive Cancer 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 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 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: Combination of Panitumumab and Bortezomib; IV panitumumab and bortezomib	Drug: Panitumumab and bortezomib; 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.; Other Names: Velcade; 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

Collaborators and Investigators

• Sponsor: Georgetown University
• Collaborators: Millennium Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): February 1, 2014
• Study Completion (ACTUAL): February 1, 2014

Study Registration Dates

• First Submitted: December 14, 2011
• First Submitted That Met QC Criteria: January 3, 2012
• First Posted (ESTIMATE): January 5, 2012

Study Record Updates

• Last Update Posted (ACTUAL): March 16, 2020
• Last Update Submitted That Met QC Criteria: March 2, 2020
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: colorectal cancer; relapsed; refractory; 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; Bortezomib; Panitumumab
• Other Study ID Numbers: 2011-033; X05374 (OTHER: Millennium Pharmaceuticals)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan for this