Back to resultsNew Individualized Therapy Trial for Metastatic Colorectal Cancer (NITMEC)
Primary Purpose
Colorectal Neoplasm, Colorectal Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Imatinib mesylate and panitumumab
Standard-of-care treatment with panitumumab
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Neoplasm focused on measuring colorectal neoplasm, colorectal cancer, imatinib mesylate, Gleevec, Physiological Effects of Drugs, panitumumab, Vectibix, c-kit receptor, Receptor, Platelet-Derived Growth Factor alpha
Eligibility Criteria
Inclusion Criteria:
- Patients ≥ 18 years of age.
- Histologically documented diagnosis of Stage IV Metastatic Colorectal Cancer with Liver Metastases, refractory or progressive after at least one (1) prior line of therapy that must include a fluoropyrimidine (5-fluorouracil or capecitabine) AND (oxaliplatin OR irinotecan), i.e. FOLFOX, FOLFIRI, XELOX, or XELIRI.
- Documentation of wild type k-Ras expression in the liver lesion.
- At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors, see Appendix 3), or other response assessment criteria, as appropriate.
- Must have ≥ 1 measurable liver lesion that can be accessed by CT guided biopsy.
- Performance status 0,1, or 2 (ECOG).
- Adequate end organ function, defined as the following: total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x UNL, creatinine < 1.5 x ULN, ANC > 1.5 x 10^9/L, platelets > 100 x 10^9/L.
- Life expectancy of at least 3 months.
- Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 7 days following discontinuation of study drug.
- Written, voluntary informed consent.
Exclusion Criteria:
- Patient has received any other investigational agents within 28 days of first day of study drug dosing, unless the disease is rapidly progressing.
- Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is neither currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
- Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
- Female patients who are pregnant or breast-feeding.
- Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
- Patient has a known brain metastasis not treated with definitive therapy with stable disease ≥ 4 weeks.
- Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
- Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
- Patient received chemotherapy within 2 weeks (6 weeks for nitrosourea or mitomycin-C)prior to study entry, unless the disease is rapidly progressing.
- Patient previously received radiotherapy to ≥ 25% of the bone marrow
- Patient had a major surgery within 2 weeks prior to study entry.
- Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
- Patients intolerant to imatinib mesylate.
Sites / Locations
- Virginia Cancer Specialists, PC
- Inova Fairfax Hospital Department of Surgery
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Imatinib mesylate and panitumumab
Panitumumab (standard-of-care)
Arm Description
Subjects whose initial liver biopsy samples meet certain lab values will be placed in Arm 1. Each participant assigned to Arm 1 will receive imatinib mesylate for 28 days, followed by a combination of imatinib mesylate and panitumumab.
Subjects whose initial liver biopsy samples meet certain lab values will be placed in Arm 2. Participants in Arm 2 will receive standard-of-care treatment with panitumumab.
Outcomes
Primary Outcome Measures
Number of Patients With Adverse Events
Information about all adverse events, whether volunteered by the subject, discovered by investigator questioning, or detected through physical examination, laboratory test or other means, will be collected and recorded.
Secondary Outcome Measures
Number of Participants With Stabilization or Reduction in Tumor Size
Results reported as number of patients with stabilization or reduction in tumor size. Tumor response is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) solid tumor response criteria, evaluated by CT.
Full Information
NCT ID
NCT00867334
First Posted
March 19, 2009
Last Updated
June 12, 2020
Sponsor
Inova Health Care Services
Collaborators
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00867334
Brief Title
New Individualized Therapy Trial for Metastatic Colorectal Cancer
Acronym
NITMEC
Official Title
A Phase I/II Study of Gleevec® Combined With Panitumumab (Vectibix®) in Patients Prescreened for C-kit/PDGFr Activated Pathways Using a Proteomic Based Assay
Study Type
Interventional
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Completed
Study Start Date
June 2009 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Inova Health Care Services
Collaborators
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of imatinib mesylate in combination with panitumumab for the treatment of stage IV colorectal cancer that has spread to the liver. It will also assess the whether imatinib mesylate, either alone or in combination with panitumumab, is effective in treating this type of cancer. In addition, the study will evaluate the feasibility of a predefined lab score and whether it can predict which patients will respond to treatment with imatinib mesylate.
Detailed Description
Recently, a series of clinical trial outcome reports have shown that KRAS mutations (and to a lesser extent KRAS mutations with BRAF V600E mutation) significantly negatively correlate with response to anti-epidermal growth factor (EGFR) mAbs, such as panitumumab, in metastatic colorectal cancer (mCRC) patients. WT KRAS status was shown to be required but not sufficient to confer sensitivity to panitumumab monotherapy. The molecular mechanisms underlying the response or lack of response to EGFR-directed therapies in CRC patients with WT RAS status are unknown. Potential mechanisms of response include activation of EGFR through receptor mutation or autocrine/paracrine ligand binding, activation while tumors that do not respond to EGFR-directed therapy may have activation of other distinct pathways such as VEGF, PDGF, and insulin-like growth factor 1 receptor; activating mutations of additional signaling proteins downstream of EGFR such as PI3K, and Src, or downstream of KRAS, such as RAF; and loss of function genes such as phosphatase and tensin homolog (PTEN). Identifying prognostic and predictive biomarkers to EGFR-directed therapy will prove important for the selection of therapeutic combinations to maximize clinical benefit. In addition to ascertaining resistance mechanisms other biomarkers such as EGFR gene copy number and expression levels of EGFR ligands in tumor cells may be useful to further refine responder population. The current approach applies to the panitumumab monotherapy and indicates that KRAS status should be considered when selecting mCRC patients as candidates for treatment. Thus, patients who are found to harbor KRAS mutation(s) as identified in the pre-treatment liver biopsy specimen will not be eligible for continuation on the trial, but following patient consent, the pre-treatment biopsy will be studied for pathway activation analysis by a CAP/CLIA compliant independent laboratory for research purposes only in the hopes for generating future hypothesis on pathway activation correlating with KRAS mutation status and help extend research into predictive pathway biomarkers for anti-EGFR therapy.
This is a two arm prospective non-randomized study that is designed to assess the safety and efficacy of Gleevec and Vectibix in the treatment of metastatic colorectal cancer to the liver. It also studies the change in phosphorylation levels of Gleevec® targets (PGDT) and tumor burden in patients treated with Gleevec® monotherapy followed by Gleevec® + Vectibix® combination therapy versus treatment with standard of care (panitumumab).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasm, Colorectal Cancer
Keywords
colorectal neoplasm, colorectal cancer, imatinib mesylate, Gleevec, Physiological Effects of Drugs, panitumumab, Vectibix, c-kit receptor, Receptor, Platelet-Derived Growth Factor alpha
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Imatinib mesylate and panitumumab
Arm Type
Experimental
Arm Description
Subjects whose initial liver biopsy samples meet certain lab values will be placed in Arm 1. Each participant assigned to Arm 1 will receive imatinib mesylate for 28 days, followed by a combination of imatinib mesylate and panitumumab.
Arm Title
Panitumumab (standard-of-care)
Arm Type
Active Comparator
Arm Description
Subjects whose initial liver biopsy samples meet certain lab values will be placed in Arm 2. Participants in Arm 2 will receive standard-of-care treatment with panitumumab.
Intervention Type
Drug
Intervention Name(s)
Imatinib mesylate and panitumumab
Other Intervention Name(s)
Gleevec, ST1571
Intervention Description
Patients will be entered into sequential cohorts with escalating doses of imatinib mesylate. After approximately 28 days of monotherapy treatment with imatinib mesylate, patients will be asked to have a liver biopsy performed (this biopsy is voluntary and is not required for continued participation in the study). All patients in this group will then receive imatinib mesylate in combination with standard-of-care doses of panitumumab. After approximately 1-2 months of combination treatment, patients will asked to have an additional liver biopsy performed (this biopsy is voluntary and is not required for continued participation in the study). Combination treatment will continue for the remainder of the subject's time in the trial.
Intervention Type
Drug
Intervention Name(s)
Standard-of-care treatment with panitumumab
Other Intervention Name(s)
Vectibix, ABX-EGF monoclonal antibody
Intervention Description
Panitumumab as standard of care. After approximately 2-3 months of standard of care treatment, patients will asked to have a liver biopsy performed (this biopsy is voluntary and is not required for continued participation in the study).
Primary Outcome Measure Information:
Title
Number of Patients With Adverse Events
Description
Information about all adverse events, whether volunteered by the subject, discovered by investigator questioning, or detected through physical examination, laboratory test or other means, will be collected and recorded.
Time Frame
From consent up until 4 weeks after patient has stopped study participation
Secondary Outcome Measure Information:
Title
Number of Participants With Stabilization or Reduction in Tumor Size
Description
Results reported as number of patients with stabilization or reduction in tumor size. Tumor response is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) solid tumor response criteria, evaluated by CT.
Time Frame
8 weeks after baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients ≥ 18 years of age.
Histologically documented diagnosis of Stage IV Metastatic Colorectal Cancer with Liver Metastases, refractory or progressive after at least one (1) prior line of therapy that must include a fluoropyrimidine (5-fluorouracil or capecitabine) AND (oxaliplatin OR irinotecan), i.e. FOLFOX, FOLFIRI, XELOX, or XELIRI.
Documentation of wild type k-Ras expression in the liver lesion.
At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors, see Appendix 3), or other response assessment criteria, as appropriate.
Must have ≥ 1 measurable liver lesion that can be accessed by CT guided biopsy.
Performance status 0,1, or 2 (ECOG).
Adequate end organ function, defined as the following: total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x UNL, creatinine < 1.5 x ULN, ANC > 1.5 x 10^9/L, platelets > 100 x 10^9/L.
Life expectancy of at least 3 months.
Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 7 days following discontinuation of study drug.
Written, voluntary informed consent.
Exclusion Criteria:
Patient has received any other investigational agents within 28 days of first day of study drug dosing, unless the disease is rapidly progressing.
Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is neither currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
Female patients who are pregnant or breast-feeding.
Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
Patient has a known brain metastasis not treated with definitive therapy with stable disease ≥ 4 weeks.
Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
Patient received chemotherapy within 2 weeks (6 weeks for nitrosourea or mitomycin-C)prior to study entry, unless the disease is rapidly progressing.
Patient previously received radiotherapy to ≥ 25% of the bone marrow
Patient had a major surgery within 2 weeks prior to study entry.
Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
Patients intolerant to imatinib mesylate.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kirsten Edmiston, MD, FACS
Organizational Affiliation
Inova Fairfax Hospital Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virginia Cancer Specialists, PC
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Inova Fairfax Hospital Department of Surgery
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
12. IPD Sharing Statement
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New Individualized Therapy Trial for Metastatic Colorectal Cancer
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