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Decision-making of ctDNA in Patients With mCRC After Failure of First-line Treatment Containing Cetuximab - a Single-center, Phase II Clinical Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04831528
Recruitment Status : Not yet recruiting
First Posted : April 5, 2021
Last Update Posted : April 5, 2021
Sponsor:
Information provided by (Responsible Party):
Fudan University

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment
Metastatic Colorectal Cancer Drug: Cetuximab Ab; Bevacizumab; Vermofenib + cetuximab;Trastuzumab+lapatinib or trastuzumab+pertuzumab; others

Study Design
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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: 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
Estimated Study Start Date : April 10, 2021
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : June 30, 2026

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
No secondary changes of drug resistance Drug: Cetuximab Ab; Bevacizumab; Vermofenib + cetuximab;Trastuzumab+lapatinib or trastuzumab+pertuzumab; others
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 Drug: Cetuximab Ab; Bevacizumab; Vermofenib + cetuximab;Trastuzumab+lapatinib or trastuzumab+pertuzumab; others
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 Drug: Cetuximab Ab; Bevacizumab; Vermofenib + cetuximab;Trastuzumab+lapatinib or trastuzumab+pertuzumab; others
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 Drug: Cetuximab Ab; Bevacizumab; Vermofenib + cetuximab;Trastuzumab+lapatinib or trastuzumab+pertuzumab; others
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 Drug: Cetuximab Ab; Bevacizumab; Vermofenib + cetuximab;Trastuzumab+lapatinib or trastuzumab+pertuzumab; others
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.


Outcome Measures
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Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   ≥18y
Accepts Healthy Volunteers:   No
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.
Criteria

Inclusion Criteria:

  1. Age ≥18, gender unlimited;
  2. Proven histologically by colorectal adenocarcinoma, local lesions can not be radical resection or metastatic colorectal cancer;
  3. Patients with RAS and BRAF wild-type tissue genetic testing, receiving first-line treatment containing cetuximab, and radiographic evaluation of disease progression;
  4. Eastern Cooperative Oncology Group (ECOG) physical condition score (PS) 0 ~ 2;
  5. Expected survival of more than 3 months;
  6. 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%;
  7. At least one measurable lesion (RECIST 1.1 criteria);
  8. 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:

  1. Have received any experimental drugs or anti-tumor drugs within 4 weeks before enrollment;
  2. 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;
  3. Patients with obvious intracranial hypertension or neuropsychiatric symptoms due to uncontrolled primary brain tumor or central nerve metastatic tumor
  4. Pregnant or lactating women;Those who are fertile but do not take adequate contraceptive measures;
  5. Alcoholism or drug addiction;
  6. with pleural effusion or ascites, causing respiratory syndrome (≥CTCAE2 grade dyspnea), requiring local treatment;
  7. 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
  8. known hypersensitivity or anaphylaxis to any component of the study drug to be applied.
  9. The function of important organs is obviously impaired
  10. Other circumstances under which the investigator considers that the patient should not participate in the study
Contacts and Locations
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Information from the National Library of Medicine

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): NCT04831528


Contacts
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Contact: Zhiyu Chen, Professor 021-64175590 chanhj75@aliyun.com

Sponsors and Collaborators
Fudan University
More Information
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Responsible Party: Fudan University
ClinicalTrials.gov Identifier: NCT04831528    
Other Study ID Numbers: FDZL-ctDNA
First Posted: April 5, 2021    Key Record Dates
Last Update Posted: April 5, 2021
Last Verified: April 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Trastuzumab
 Cetuximab
Pertuzumab
Lapatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action