Colorectal Cancer Clinical Trial
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
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.
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).
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05400122 -
Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer
|
Phase 1 | |
Active, not recruiting |
NCT05551052 -
CRC Detection Reliable Assessment With Blood
|
||
Completed |
NCT00098787 -
Bevacizumab and Oxaliplatin Combined With Irinotecan or Leucovorin and Fluorouracil in Treating Patients With Metastatic or Recurrent Colorectal Cancer
|
Phase 2 | |
Recruiting |
NCT06037954 -
A Study of Mental Health Care in People With Cancer
|
N/A | |
Recruiting |
NCT05425940 -
Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer
|
Phase 3 | |
Suspended |
NCT04595604 -
Long Term Effect of Trimodal Prehabilitation Compared to ERAS in Colorectal Cancer Surgery.
|
N/A | |
Completed |
NCT03414125 -
Effect of Mailed Invites of Choice of Colonoscopy or FIT vs. Mailed FIT Alone on Colorectal Cancer Screening
|
N/A | |
Completed |
NCT02963831 -
A Study to Investigate ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies
|
Phase 1/Phase 2 | |
Recruiting |
NCT05489211 -
Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)
|
Phase 2 | |
Terminated |
NCT01847599 -
Educational Intervention to Adherence of Patients Treated by Capecitabine +/- Lapatinib
|
N/A | |
Completed |
NCT05799976 -
Text Message-Based Nudges Prior to Primary Care Visits to Increase Care Gap Closure
|
N/A | |
Recruiting |
NCT03874026 -
Study of Folfiri/Cetuximab in FcGammaRIIIa V/V Stage IV Colorectal Cancer Patients
|
Phase 2 | |
Active, not recruiting |
NCT03170960 -
Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors
|
Phase 1/Phase 2 | |
Completed |
NCT03181334 -
The C-SPAN Coalition: Colorectal Cancer Screening and Patient Navigation
|
N/A | |
Completed |
NCT03167125 -
Participatory Research to Advance Colon Cancer Prevention
|
N/A | |
Recruiting |
NCT04258137 -
Circulating DNA to Improve Outcome of Oncology PatiEnt. A Randomized Study
|
N/A | |
Recruiting |
NCT05568420 -
A Study of the Possible Effects of Medication on Young Onset Colorectal Cancer (YOCRC)
|
||
Recruiting |
NCT02972541 -
Neoadjuvant Chemotherapy Verse Surgery Alone After Stent Placement for Obstructive Colonic Cancer
|
N/A | |
Completed |
NCT02876224 -
Study of Cobimetinib in Combination With Atezolizumab and Bevacizumab in Participants With Gastrointestinal and Other Tumors
|
Phase 1 | |
Completed |
NCT01943500 -
Collection of Blood Specimens for Circulating Tumor Cell Analysis
|
N/A |