- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04831528
Decision-making of ctDNA in Patients With mCRC After Failure of First-line Treatment Containing Cetuximab - a Single-center, Phase II Clinical Study
April 2, 2021 updated by: Fudan University
The Role of Circulating Tumor DNA in Decision-making of Patients With Metastatic Colorectal Cancer After Failure of First-line Treatment Containing Cetuximab - a Single-center, Phase II Clinical Study
This study aimis at detecting the genomic changes of ctDNA in patients of RAS and BRAF wild-type mCRC, who failed after first line treatment containing cetuximab.
According to the results of ctDNA detection, individualized second-line targeted therapy strategies were developed to explore the disease control rate and prognostic significance of ctDNA-guided treatment for metastatic colorectal cancer.
Study Overview
Status
Not yet recruiting
Conditions
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.
Study Contact
- Name: Zhiyu Chen, Professor
- Phone Number: 021-64175590
- Email: chanhj75@aliyun.com
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 and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Probability Sample
Study Population
Patients who met the entry criteria, failed after receiving first-line treatment containing cetuximab, and were judged to have progressive disease (PD) by imaging evaluation were eligible for inclusion.
Description
Inclusion Criteria:
- Age ≥18, gender unlimited;
- Proven histologically by colorectal adenocarcinoma, local lesions can not be radical resection or metastatic colorectal cancer;
- Patients with RAS and BRAF wild-type tissue genetic testing, receiving first-line treatment containing cetuximab, and radiographic evaluation of disease progression;
- Eastern Cooperative Oncology Group (ECOG) physical condition score (PS) 0 ~ 2;
- Expected survival of more than 3 months;
- Within 7 days before screening (including 7 days), laboratory test data requirements were as follows: neutrophil count ≥1.5×109/L, platelet count ≥100×109/L, hemoglobin ≥90g/L (no blood transfusion within 14 days), serum total bilirubin ≤1.25 times the upper normal limit (ULN);ALT and AST≤ 2.5 x ULN (≤5x ULN in patients with liver metastasis);Serum creatinine ≤1.0 x ULN and creatinine clearance rate ≥60 mL /min;Left ventricular ejection fraction in ultrasound examination >55%;
- At least one measurable lesion (RECIST 1.1 criteria);
- Subjects (or their legal representative/guardian) must sign the informed consent indicating that they understand the purpose of the study, understand the necessary procedures of the study, and are willing to participate in the study.
Exclusion Criteria:
Those who have one or more of the following will not be included in the study:
- Have received any experimental drugs or anti-tumor drugs within 4 weeks before enrollment;
- A history of other tumors in the past five years, except for cervix cancer or basal cell carcinoma of the skin that has been cured;
- Patients with obvious intracranial hypertension or neuropsychiatric symptoms due to uncontrolled primary brain tumor or central nerve metastatic tumor
- Pregnant or lactating women;Those who are fertile but do not take adequate contraceptive measures;
- Alcoholism or drug addiction;
- with pleural effusion or ascites, causing respiratory syndrome (≥CTCAE2 grade dyspnea), requiring local treatment;
- Patients with the following serious or uncontrolled diseases: severe heart disease, unstable condition after treatment, myocardial infarction, congestive heart failure, unstable angina pectoris, pericardial effusion with obvious symptoms or unstable arrhythmia within 6 months before enrollment;Definite neuropathy or psychosis, including dementia or seizures;Severe or uncontrolled infections;Patients with active and disseminated intravascular coagulation and significant bleeding tendency
- known hypersensitivity or anaphylaxis to any component of the study drug to be applied.
- The function of important organs is obviously impaired
- Other circumstances under which the investigator considers that the patient should not participate in the study
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 |
---|---|
No secondary changes of drug resistance
|
After PD, patients received ctDNA testing, and different research protocols were selected according to different gene states of ctDNA, as follows: 1.No secondary changes related to drug resistance were found.
Cetuximab cross-line + second-line chemotherapy (FOLFOX/FOLFIRI/ Irinotecan monotherapy, etc.) was used.2.
If there is a RAS secondary mutation, change of beacizumab bead sheet resistance + second-line chemotherapy (FOLFOX/XELOX/stand for kang single-agent FOLFIRI mXEIRI/Iraq, etc.);3.
If BRAF secondary mutation occurs, replace it with vimofenib + cetuximab + irinotecan;4.
If HER2 amplification occurs, replace it with trastuzumab + lapatinib or trastuzumab + pertuzumab;5.
In case of other secondary mutations, bevacizumab plus second-line chemotherapy should be replaced.
|
Secondary mutations of RAS
|
After PD, patients received ctDNA testing, and different research protocols were selected according to different gene states of ctDNA, as follows: 1.No secondary changes related to drug resistance were found.
Cetuximab cross-line + second-line chemotherapy (FOLFOX/FOLFIRI/ Irinotecan monotherapy, etc.) was used.2.
If there is a RAS secondary mutation, change of beacizumab bead sheet resistance + second-line chemotherapy (FOLFOX/XELOX/stand for kang single-agent FOLFIRI mXEIRI/Iraq, etc.);3.
If BRAF secondary mutation occurs, replace it with vimofenib + cetuximab + irinotecan;4.
If HER2 amplification occurs, replace it with trastuzumab + lapatinib or trastuzumab + pertuzumab;5.
In case of other secondary mutations, bevacizumab plus second-line chemotherapy should be replaced.
|
Secondary mutation of BRAF
|
After PD, patients received ctDNA testing, and different research protocols were selected according to different gene states of ctDNA, as follows: 1.No secondary changes related to drug resistance were found.
Cetuximab cross-line + second-line chemotherapy (FOLFOX/FOLFIRI/ Irinotecan monotherapy, etc.) was used.2.
If there is a RAS secondary mutation, change of beacizumab bead sheet resistance + second-line chemotherapy (FOLFOX/XELOX/stand for kang single-agent FOLFIRI mXEIRI/Iraq, etc.);3.
If BRAF secondary mutation occurs, replace it with vimofenib + cetuximab + irinotecan;4.
If HER2 amplification occurs, replace it with trastuzumab + lapatinib or trastuzumab + pertuzumab;5.
In case of other secondary mutations, bevacizumab plus second-line chemotherapy should be replaced.
|
HER2 amplification
|
After PD, patients received ctDNA testing, and different research protocols were selected according to different gene states of ctDNA, as follows: 1.No secondary changes related to drug resistance were found.
Cetuximab cross-line + second-line chemotherapy (FOLFOX/FOLFIRI/ Irinotecan monotherapy, etc.) was used.2.
If there is a RAS secondary mutation, change of beacizumab bead sheet resistance + second-line chemotherapy (FOLFOX/XELOX/stand for kang single-agent FOLFIRI mXEIRI/Iraq, etc.);3.
If BRAF secondary mutation occurs, replace it with vimofenib + cetuximab + irinotecan;4.
If HER2 amplification occurs, replace it with trastuzumab + lapatinib or trastuzumab + pertuzumab;5.
In case of other secondary mutations, bevacizumab plus second-line chemotherapy should be replaced.
|
Other secondary mutations
|
After PD, patients received ctDNA testing, and different research protocols were selected according to different gene states of ctDNA, as follows: 1.No secondary changes related to drug resistance were found.
Cetuximab cross-line + second-line chemotherapy (FOLFOX/FOLFIRI/ Irinotecan monotherapy, etc.) was used.2.
If there is a RAS secondary mutation, change of beacizumab bead sheet resistance + second-line chemotherapy (FOLFOX/XELOX/stand for kang single-agent FOLFIRI mXEIRI/Iraq, etc.);3.
If BRAF secondary mutation occurs, replace it with vimofenib + cetuximab + irinotecan;4.
If HER2 amplification occurs, replace it with trastuzumab + lapatinib or trastuzumab + pertuzumab;5.
In case of other secondary mutations, bevacizumab plus second-line chemotherapy should be replaced.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate
Time Frame: April 10,2021-June 30,2021
|
The percentage of patients whose tumors shrink by a certain amount and remain so for a certain amount of time, including patients with CR and PR.Objective tumor response was assessed using the Response Assessment Criterion for Solid Tumors (RECIST 1.1).
|
April 10,2021-June 30,2021
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
overall survival
Time Frame: April 10,2021-June 30,2021
|
Time from enrollment to death from any cause.Lost visitors to the last follow-up time.
|
April 10,2021-June 30,2021
|
progress free survival
Time Frame: April 10,2021-June 30,2021
|
Patients were randomized to solstice for any recorded time of tumor progression or death from any cause.
|
April 10,2021-June 30,2021
|
Safety and tolerability
Time Frame: April 10,2021-June 30,2021
|
NCI -- CTC AE 4.0 will be used to evaluate the clinical safety of the treatment in the study.The incidence of adverse events in the subjects should be assessed at each clinical visit.
|
April 10,2021-June 30,2021
|
duration of response
Time Frame: April 10,2021-June 30,2021
|
This is the time between the first assessment of a tumor as CR or PR and the first assessment as PD or death from any cause.
|
April 10,2021-June 30,2021
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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 (Anticipated)
April 10, 2021
Primary Completion (Anticipated)
June 30, 2025
Study Completion (Anticipated)
June 30, 2026
Study Registration Dates
First Submitted
April 2, 2021
First Submitted That Met QC Criteria
April 2, 2021
First Posted (Actual)
April 5, 2021
Study Record Updates
Last Update Posted (Actual)
April 5, 2021
Last Update Submitted That Met QC Criteria
April 2, 2021
Last Verified
April 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Protein Kinase Inhibitors
- Trastuzumab
- Bevacizumab
- Cetuximab
- Lapatinib
- Pertuzumab
Other Study ID Numbers
- FDZL-ctDNA
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
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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