New Individualized Therapy Trial for Metastatic Colorectal Cancer (NITMEC)
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|ClinicalTrials.gov Identifier: NCT00867334|
Recruitment Status : Completed
First Posted : March 23, 2009
Results First Posted : September 9, 2019
Last Update Posted : September 9, 2019
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Neoplasm Colorectal Cancer||Drug: Imatinib mesylate and panitumumab Drug: Standard-of-care treatment with panitumumab||Phase 1 Phase 2|
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).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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 Start Date :||June 2009|
|Actual Primary Completion Date :||August 2011|
|Actual Study Completion Date :||August 2011|
Experimental: Imatinib mesylate and panitumumab
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.
Drug: Imatinib mesylate and panitumumab
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.
Active Comparator: Panitumumab (standard-of-care)
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.
Drug: Standard-of-care treatment with panitumumab
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).
- Number of Patients With Adverse Events [ Time Frame: From consent up until 4 weeks after patient has stopped study participation ]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.
- Number of Participants With Stabilization or Reduction in Tumor Size [ Time Frame: 8 weeks after baseline ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00867334
|United States, Virginia|
|Virginia Cancer Specialists, PC|
|Fairfax, Virginia, United States, 22031|
|Inova Fairfax Hospital Department of Surgery|
|Falls Church, Virginia, United States, 22042|
|Principal Investigator:||Kirsten Edmiston, MD, FACS||Inova Fairfax Hospital Cancer Center|