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Panitumumab and Bortezomib for Patients With Advanced Colorectal Cancer

Primary Purpose

Colorectal Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Panitumumab and bortezomib
Sponsored by
Georgetown University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring colorectal cancer, relapsed, refractory, Kras wild type

Eligibility Criteria

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

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)

Sites / Locations

  • Georgetown Lombardi Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Combination of Panitumumab and Bortezomib

Arm Description

IV panitumumab and bortezomib

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose
The maximum tolerated dose of bortezomib (to be used in combination with panitumumab)
Maximum Tolerated Dose
The maximum tolerated dose of panitumumab (to be used in combination with bortezomib)

Secondary Outcome Measures

Percent of Patients With Disease Control
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
Partial response plus complete response as per RECIST v1.0
Duration of Disease Control
Time from study registration until progressive disease

Full Information

First Posted
December 14, 2011
Last Updated
March 2, 2020
Sponsor
Georgetown University
Collaborators
Millennium Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01504477
Brief Title
Panitumumab and Bortezomib for Patients With Advanced Colorectal Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Terminated
Why Stopped
Low accrual--unable to meet accrual goals
Study Start Date
December 2011 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
February 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Georgetown University
Collaborators
Millennium Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
colorectal cancer, relapsed, refractory, Kras wild type

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Combination of Panitumumab and Bortezomib
Arm Type
Experimental
Arm Description
IV panitumumab and bortezomib
Intervention Type
Drug
Intervention Name(s)
Panitumumab and bortezomib
Other Intervention Name(s)
Velcade, Vectibix
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose
Description
The maximum tolerated dose of bortezomib (to be used in combination with panitumumab)
Time Frame
12 months
Title
Maximum Tolerated Dose
Description
The maximum tolerated dose of panitumumab (to be used in combination with bortezomib)
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Percent of Patients With Disease Control
Description
Stable disease after 2 cycles, partial response or complete response as determined by RECIST v1.0
Time Frame
16 weeks
Title
Percent of of Patients With a Complete or Partial Response
Description
Partial response plus complete response as per RECIST v1.0
Time Frame
16 weeks
Title
Duration of Disease Control
Description
Time from study registration until progressive disease
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Pishvaian, MD PhD
Organizational Affiliation
Georgetown University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Georgetown Lombardi Comprehensive Cancer Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is no plan for this

Learn more about this trial

Panitumumab and Bortezomib for Patients With Advanced Colorectal Cancer

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