Evaluation of CTCs Combined With Tumor Marker Detection of Efficacy of Chemotherapy in mCRC
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|ClinicalTrials.gov Identifier: NCT02948985|
Recruitment Status : Unknown
Verified October 2016 by Qi Li, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine.
Recruitment status was: Not yet recruiting
First Posted : October 31, 2016
Last Update Posted : November 1, 2016
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|Condition or disease||Intervention/treatment|
|Colorectal Cancer Metastatic||Other: treated with FOLFIRI±cetuximab|
In 2004, based on AVF2107g clinical research, FDA has approved bevacizumab as first targeted drugs for the treatment of advanced colorectal cancer.So far, chemotherapy combined with target agents is currently first line standard of patients with advanced colorectal cancer. The anti-EGFR monoclonal antibodies((cetuximab and panitumumab) also have been demonstrated to be efficient in the treatment of metastatic colorectal cancer. In the CRYSTAL and OPUS studies, adding cetuximab to first-line chemotherapy (CT) improved clinical benefit in patients (pts) with KRAS wild-type (wt) mCRC [2,3]. FIRE-3 and TAILOR once again proved cetuximab combined FORFIRI or FOLFOX will improved clinical benefit. Target agents are expensive, so It is necessary to explore a new evaluation criteria to avoid unnecessary economic waste.
RECIST(Response Evaluation Criteria in Solid Tumors) is not suitable for the target or immunotherapy. The effect of chemotherapy not only displayed as morphology(tumor size reduction), but also as the biological activity change of tumor cells(e.g.cystic degeneration and cavity).PET-CT combined imaging of molecular function and morphology, but PET-CT was low cost -effective. The tumor markers is a rapid, easy to repeat method, but the change of the markers can not evaluation the response of tumor as an individual indicator. So we need a more sensitive effective evaluation marker.
Circulating tumor cells (CTCs) are rare cancer cells released from tumors into the bloodstream that are thought to have a key role in cancer metastasis. The distant metastasis is the leading cause of death in patients with mCRC. CTCs is a method to detect the early tumor micrometastasis. CTCs is predictive of PFS and OS in lung cancer and breast cancer. CTCs is also predictive of response of tumor. CTCs is more accuracy, more sensitive way than imageology or other tumor marker to predict therapy effect and outcome.
The anti-EGFR monoclonal antibody (cetuximab) target the human epidermal growth factor receptor and have been integrated into treatment regimens of mCRC. The EGFR expression is not the predicted marker of cetuximab, in patients who express EGFR, the ORR only 10%-20%[5,6].In CRYSTAL, The addition of cetuximab to FOLFIRI as first-line therapy improves PFS in patients with KRASwild-type mCRC. Up to now, we know only RAS wild type patients would benefit from anti-EGFR therapy. The CALGB/SWOG80405 confirmed the conclusion. Some study also found the patients with B-raf (V600e) mutation would not benefit from anti-EGFR therapy. Taken together, we need a more accuracy, more sensitive method to predict the effect of cetuximab.
The study is a single arm, single-center, observational study undertaken in anticipated 100 patients with histologically confirmed RAS and B-raf wild type mCRC. These patients received FOLFIRI±cetuximab therapy.
Peripheral blood samples of 10 mL were collected from the patients for CTCs analysis and tumor marker in every cycle D0 and D8. The CTCs sued the integrated subtraction enrichment (SET) and immunostaining-fluorescence in situ hybridization (iFISH) platform.Tumor assessments will be performed every four cycles based on RECIST v1.1 criteria using CT/MRI scan. If the assessments are inconsistent, we will collect 10ml peripheral blood for ct DNA test, which using BEAMing, to analyze mutant gene.
The correlation of the RAS status on CTCs and the mutant gene in ctDNA to the therapeutic response will be evaluated, and found the cut-off of CTCs.
|Study Type :||Observational [Patient Registry]|
|Estimated Enrollment :||100 participants|
|Target Follow-Up Duration:||3 Years|
|Official Title:||Evaluation of Individual Peripheral Blood Circulating Tumor Cells Combined With Tumor Marker Detection of Efficacy of Chemotherapy in Patients With Advanced Colorectal Cancer: A Observational Clinical Trial|
|Study Start Date :||January 2017|
|Estimated Primary Completion Date :||July 2019|
|Estimated Study Completion Date :||December 2019|
RAS and B-raf wild type mCRC
patients with histologically confirmed RAS and B-raf wild type mCRC treated with FOLFIRI±cetuximab
Other: treated with FOLFIRI±cetuximab
Peripheral blood samples of 10 mL were collected from the patients for CTCs analysis and tumor marker in every cycle D0 and D8. Tumor response evaluation will be performed after four cycles of chemotherapy by CT/MRI based on RECIST. Clinical data, including tumor stage, metastatic organ, objective response, progression free survival, overall survival, etc, will be collected according to study protocol.The correlation of the RAS status on CTCs and the mutant gene in ctDNA to the therapeutic response will be evaluated.
- Correlation of RAS status on CTCs with clinical outcomes [ Time Frame: 3 years ]To evaluate the correlation of CTCs and their RAS status to the clinical outcomes
- Correlation of mutant gene in ctDNA with cetuximab resistance. [ Time Frame: 3 years ]To evaluate the correlation of mutant gene in ctDNA to the cetuximab resistance
Biospecimen Retention: Samples With DNA
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|Ages Eligible for Study:||18 Years to 75 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
|Sampling Method:||Probability Sample|
- Having signed informed consent
- Age18-75 years old
- Histologically confirmed mCRC
- First metastatic,unresectable
- RAS and B-raf wild type
- .At least one measurable disease according to the RECIST criteria by CT/MRI
- Expected survival time≥12 weeks
- ECOG PS 0-1
- Adequate bone marrow, hepatic, renal and metabolic function
- Received chemotherapy for CRC previously, except adjuvant chemotherapy end of adjuvant chemotherapy≥9m(contain irinotecan) or ≥9m(not contain irinotecan) before the study.
- Surgery or radiotherapy ≤30 days before the study.
- Received anti-EGFR,anti-VEGF or other signaling pathway inhibitor previously
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): NCT02948985
|Contact: Li Qi, MD PHD||+8618121288167||Leeqi2001@hotmail.com|
|Contact: Zhang Haiyan, MD||+8613611956117||Zhymmx@sina.com|
|Study Chair:||Wang Xingpeng, MD PHD||Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine|
Publications of Results:
|Responsible Party:||Qi Li, Executive director of cancer center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine|
|Other Study ID Numbers:||
|First Posted:||October 31, 2016 Key Record Dates|
|Last Update Posted:||November 1, 2016|
|Last Verified:||October 2016|
Metastatic colorectal cancer
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Antineoplastic Agents, Immunological