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

• ClinicalTrials.gov Identifier: NCT04831528
• Recruitment Status: Not yet recruiting
• First Posted: April 5, 2021
• Last Update Posted: April 5, 2021
• Sponsor: Fudan University
• Information provided by (Responsible Party): Fudan University

Tracking Information

• First Submitted Date: April 2, 2021
• First Posted Date: April 5, 2021
• Last Update Posted Date: April 5, 2021
• Estimated Study Start Date: April 10, 2021
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 2, 2021)

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).

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: April 2, 2021)

• 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.
• 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.
• 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.
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Decision-making of ctDNA in Patients With mCRC After Failure of First-line Treatment Containing Cetuximab - a Single-center, Phase II Clinical Study
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• 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.
• Condition: Metastatic Colorectal Cancer

Intervention

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.

Study Groups/Cohorts

• No secondary changes of drug resistance
  Intervention: Drug: Cetuximab Ab; Bevacizumab; Vermofenib + cetuximab;Trastuzumab+lapatinib or trastuzumab+pertuzumab; others
• Secondary mutations of RAS
  Intervention: Drug: Cetuximab Ab; Bevacizumab; Vermofenib + cetuximab;Trastuzumab+lapatinib or trastuzumab+pertuzumab; others
• Secondary mutation of BRAF
  Intervention: Drug: Cetuximab Ab; Bevacizumab; Vermofenib + cetuximab;Trastuzumab+lapatinib or trastuzumab+pertuzumab; others
• HER2 amplification
  Intervention: Drug: Cetuximab Ab; Bevacizumab; Vermofenib + cetuximab;Trastuzumab+lapatinib or trastuzumab+pertuzumab; others
• Other secondary mutations
  Intervention: Drug: Cetuximab Ab; Bevacizumab; Vermofenib + cetuximab;Trastuzumab+lapatinib or trastuzumab+pertuzumab; others

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: April 2, 2021): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2026
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: ≥18y

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04831528
• Other Study ID Numbers: FDZL-ctDNA
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Fudan University
• Original Responsible Party: Same as current
• Current Study Sponsor: Fudan University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Fudan University
• Verification Date: April 2021