Panitumumab and Bortezomib for Patients With Advanced Colorectal Cancer

This study has been terminated.
(Low accrual--unable to meet accrual goals)
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Georgetown University
ClinicalTrials.gov Identifier:
NCT01504477
First received: December 14, 2011
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Drug: Panitumumab and bortezomib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Georgetown University:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    The maximum tolerated dose of bortezomib to be used in combination with panitumumab


Secondary Outcome Measures:
  • Disease control rate [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Stable disease after 2 cycles, partial response or complete response

  • Overall response rate [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Partial response plus complete response

  • Overall survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Time from study registration to death

  • Duration of disease control [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Time from study registration until progressive disease

  • Pharmacodynamic effects [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
    pharmacodynamic effects of panitumumab alone and in combination with bortezomib on the EGFR and proteosome pathways by phosphoprotein pathway analysis


Enrollment: 6
Study Start Date: December 2011
Estimated Study Completion Date: September 2015
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01504477

Locations
United States, District of Columbia
Georgetown Lombardi Comprehensive Cancer Center
Washington, District of Columbia, United States, 20007
Sponsors and Collaborators
Georgetown University
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Michael Pishvaian, MD PhD Georgetown University
  More Information

No publications provided

Responsible Party: Georgetown University
ClinicalTrials.gov Identifier: NCT01504477     History of Changes
Other Study ID Numbers: 2011-033, X05374
Study First Received: December 14, 2011
Last Updated: February 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Georgetown University:
colorectal cancer
relapsed
refractory
Kras wild type

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antibodies, Monoclonal
Bortezomib
Cetuximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014