Evaluation of CTCs Combined With Tumor Marker Detection of Efficacy of Chemotherapy in mCRC

October 31, 2016 updated by: Qi Li, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

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

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 Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

In 2004, based on AVF2107g clinical research, FDA has approved bevacizumab as first targeted drugs for the treatment of advanced colorectal cancer[1].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[4]. 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[2]. Up to now, we know only RAS wild type patients would benefit from anti-EGFR therapy.[7] The CALGB/SWOG80405 confirmed the conclusion. Some study also found the patients with B-raf (V600e) mutation would not benefit from anti-EGFR therapy[8]. 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

Enrollment (Anticipated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients with histologically confirmed RAS and B-raf wild type mCRC treated withFOLFIRI±cetuximab

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Investigators

  • Study Chair: Wang Xingpeng, MD PHD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2017

Primary Completion (Anticipated)

July 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

October 27, 2016

First Submitted That Met QC Criteria

October 27, 2016

First Posted (Estimate)

October 31, 2016

Study Record Updates

Last Update Posted (Estimate)

November 1, 2016

Last Update Submitted That Met QC Criteria

October 31, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Shanghai1stQli01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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