Colorectal Cancer
Conditions
Keywords
colorectal cancer, relapsed, refractory, Kras wild type
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.
Interventions
DRUGPanitumumab 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.
Sponsors
Millennium Pharmaceuticals, Inc.
Georgetown University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose | 12 months | The maximum tolerated dose of bortezomib (to be used in combination with panitumumab) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Combination of Panitumumab and Bortezomib IV panitumumab and bortezomib
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. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Combination of Panitumumab and Bortezomib |
|---|---|
| Age, Continuous | 60.83 years STANDARD_DEVIATION 5.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Maximum Tolerated Dose
The maximum tolerated dose of bortezomib (to be used in combination with panitumumab)
Time frame: 12 months
Population: The maximally tolerated dose of bortezomib weekly to be used in combination with with Panitumumab every 2 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination of Panitumumab and Bortezomib | Maximum Tolerated Dose | 1.6 mg/m2 |
Primary
Maximum Tolerated Dose
The maximum tolerated dose of panitumumab (to be used in combination with bortezomib)
Time frame: 12 months
Population: The maximum tolerated dose of panitumumab (to be used in combination with bortezomib)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination of Panitumumab and Bortezomib | Maximum Tolerated Dose | 6 mg/kg |
Secondary
Duration of Disease Control
Time from study registration until progressive disease
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combination of Panitumumab and Bortezomib | Duration of Disease Control | 35.5 Days |
Secondary
Percent of of Patients With a Complete or Partial Response
Partial response plus complete response as per RECIST v1.0
Time frame: 16 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combination of Panitumumab and Bortezomib | Percent of of Patients With a Complete or Partial Response | 0 Participants |
Secondary
Percent of Patients With Disease Control
Stable disease after 2 cycles, partial response or complete response as determined by RECIST v1.0
Time frame: 16 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination of Panitumumab and Bortezomib | Percent of Patients With Disease Control | 0 percentage of participants |