ctDNA-Guided Therapy for Colorectal Cancer

Overseen By Michael White, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Investigational agents

Disqualifiers: Brain metastases, Uncontrolled illness, Psychiatric illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

48 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

What data supports the effectiveness of the treatment Circulating tumoral DNA directed neoadjuvant therapy for colorectal cancer?

Research shows that using circulating tumor DNA (ctDNA) can help guide more precise treatment for colorectal cancer by monitoring genetic changes, predicting treatment response, and assessing minimal residual disease. This approach can improve treatment decisions and potentially lead to better outcomes for patients. ^{1 2 3 4 5}

Is ctDNA-guided therapy safe for humans?

The use of circulating tumor DNA (ctDNA) in cancer treatment is considered safe because it is a noninvasive method that involves analyzing DNA from the blood, rather than performing more invasive procedures like tissue biopsies. It has been used for monitoring and guiding treatment in various cancers, including colorectal cancer, without reported safety concerns. ^{1 2 6 7 8}

What makes ctDNA-guided therapy unique for colorectal cancer treatment?

ctDNA-guided therapy is unique because it uses a liquid biopsy, which is a simple blood test, to detect and monitor tumor DNA in the bloodstream. This allows for a noninvasive, precise, and personalized approach to treatment, helping to tailor therapy based on the specific genetic changes in a patient's cancer. ^{1 2 8 9 10}

What is the purpose of this trial?

To learn if circulating tumor DNA (ctDNA) testing before cytoreductive surgery (CRS) with or without heated intraperitoneal chemotherapy (HIPEC) can show if patients have a low or high risk of the disease returning and help doctors decide if less or more intense chemotherapy is needed as treatment before surgery. ctDNA testing measures the amount of tumor DNA (genetic information) in the blood.

Research Team

Michael White, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults over 18 with moderate or poorly differentiated appendiceal or colorectal adenocarcinoma, visible metastatic peritoneal disease, and good performance status. They must have adequate organ function and not be pregnant, agreeing to use contraception. Excluded are those with recent chemotherapy/radiotherapy, uncontrolled illnesses, major surgery within the last month, brain metastases, or other conditions that could affect study participation.

Inclusion Criteria

I can communicate in English or another language.

I have another cancer that won't affect this treatment's safety or results.

My cancer has spread to the lining of my abdomen and can be seen during a laparoscopy.

Exclusion Criteria

Pregnant women

Patients with psychiatric illness/social situations that would limit compliance with study requirements

My cancer has spread to my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant chemotherapy tailored based on ctDNA levels to direct the duration of therapy

8-12 weeks

Regular visits for ctDNA measurement and chemotherapy administration

Surgery

Participants undergo cytoreductive surgery (CRS) with or without heated intraperitoneal chemotherapy (HIPEC)

1 week

1 visit (in-person) for surgery

Follow-up

Participants are monitored for recurrence-free survival and overall survival, with ctDNA levels assessed post-resection

2 years

Regular follow-up visits for monitoring and ctDNA assessment

Treatment Details

Interventions

• Circulating tumoral DNA directed neoadjuvant therapy

Trial Overview The study tests if ctDNA levels before cytoreductive surgery can predict cancer recurrence risk in patients with colorectal or appendiceal adenocarcinoma. This helps determine the intensity of neoadjuvant chemotherapy needed prior to surgery.

Participant Groups

Group I: Circulating tumoral DNA directed neoadjuvant therapy arm Experimental Treatment 1 Intervention

Participants will have their circulating tumoral DNA levels measured at the onset of neoadjuvant chemotherapy and during their neoadjuvant treatment to direct the duration of therapy provided.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

Circulating tumor DNA detection is a quick, low-cost, and reliable method for liquid biopsy, making it a valuable tool for noninvasive cancer screening and monitoring.

In colorectal cancer, monitoring circulating tumor DNA can help assess prognosis, track resistance to treatments, evaluate therapeutic effects, and guide more precise targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Circulating tumor DNA and targeted therapy in colorectal cancer]. Huang, YT., Xu, JM.[2018]

Circulating tumor DNA (ctDNA) is a highly specific and increasingly sensitive marker that can predict recurrence and survival in early stage colon cancer, making it a valuable tool for monitoring patients after surgery and chemotherapy.

Ongoing trials are exploring how ctDNA analysis can guide treatment decisions, potentially allowing for personalized therapy adjustments based on ctDNA status, which could significantly improve outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating tumor DNA (ctDNA) in adjuvant therapy of early stage colon cancer: current status and future perspectives. Merk, C., Martling, A., Lindberg, J., et al.[2022]

Circulating tumor DNA (ctDNA) has shown promise in detecting colorectal cancer (CRC) signals in both non-metastatic and metastatic cases, with ongoing phase III trials assessing its role in managing CRC.

ctDNA assays could significantly impact clinical practice by guiding treatment strategies, such as adjusting adjuvant therapy in early-stage CRC and predicting responses to therapies in advanced cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Applications of Minimal Residual Disease Assessments by Tumor-Informed and Tumor-Uninformed Circulating Tumor DNA in Colorectal Cancer. Gong, J., Hendifar, A., Gangi, A., et al.[2022]

Circulating tumor DNA (ctDNA) was detected in 69% of patients with rectal cancer before treatment, but this dropped to only 15% after neoadjuvant therapy, indicating a significant response to treatment.

The presence of ctDNA after neoadjuvant therapy and surgery was linked to worse progression-free survival, suggesting that ctDNA detection could be a valuable tool for predicting treatment outcomes and guiding further management in rectal cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating tumor DNA detection after neoadjuvant treatment and surgery predicts recurrence in patients with early-stage and locally advanced rectal cancer. Hofste, LSM., Geerlings, MJ., von Rhein, D., et al.[2023]

Circulating tumor DNA (ctDNA) is emerging as a promising biomarker for assessing minimal residual disease (MRD) in patients with resected colorectal cancer, potentially offering more precise risk stratification than traditional methods.

Current studies suggest that ctDNA could outperform existing clinicopathologic criteria in identifying patients with MRD, and ongoing clinical trials aim to validate ctDNA-guided treatment strategies that could significantly change how adjuvant therapy is administered for colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finding Waldo: The Evolving Paradigm of Circulating Tumor DNA (ctDNA)-Guided Minimal Residual Disease (MRD) Assessment in Colorectal Cancer (CRC). Chakrabarti, S., Kasi, AK., Parikh, AR., et al.[2022]

The study developed and validated mutation-specific digital droplet PCR (ddPCR) assays for detecting circulating tumor DNA (ctDNA) in 352 plasma samples from 96 patients with solid tumors, showing high sensitivity and specificity that aligns well with tumor sequencing results.

ctDNA profiling not only allowed for effective disease monitoring and detection of resistance mutations but also facilitated personalized treatment selection by identifying actionable gene targets, indicating its potential for routine use in cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized Treatment Selection and Disease Monitoring Using Circulating Tumor DNA Profiling in Real-World Cancer Patient Management. Wehrle, J., Philipp, U., Jolic, M., et al.[2020]

In a case study of a patient with metastatic colorectal cancer, liquid biopsy using the Idylla© Biocartis system revealed no mutations in KRAS, NRAS, or BRAF genes, which is significant for guiding targeted therapy decisions.

Following the liquid biopsy results, the patient received a third line of palliative chemotherapy with irinotecan and cetuximab, leading to a partial response and improved progression-free survival, highlighting the potential of ctDNA analysis in optimizing treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic impact of determination of RAS mutations in the plasma of patient with colorectal cancer. Macedo, F., Monteiro, J., Pereira, TC., et al.[2022]

Circulating tumor DNA (ctDNA) is a promising minimally invasive tool for cancer diagnostics and treatment, allowing for early tumor detection and monitoring of treatment response.

ctDNA can help identify minimal residual disease and assess therapy resistance, potentially improving therapeutic outcomes compared to traditional tissue biopsies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toward liquid biopsies in cancer treatment: application of circulating tumor DNA. Barlebo Ahlborn, L., Østrup, O.[2019]

A new microarray method was developed to detect BRAF V600 mutations in circulating tumor DNA (ctDNA) from melanoma patients, achieving sensitivity to detect as little as 0.05% mutated DNA.

The presence of BRAF mutations in ctDNA significantly correlated with tumor progression in patients undergoing therapy, indicating that ctDNA analysis can be a valuable non-invasive tool for monitoring disease status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microarray-based analysis of the BRAF V600 mutations in circulating tumor DNA in melanoma patients. Emelyanova, MA., Telysheva, EN., Orlova, KV., et al.[2021]

Circulating tumor DNA (ctDNA) serves as a promising 'liquid biopsy' tool that can provide insights into tumor evolution and genetic alterations, allowing for personalized treatment strategies in various cancers.

ctDNA analysis can help in patient stratification, monitoring treatment responses, and enabling early interventions, making it a valuable resource in the shift towards precision medicine in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Perspectives on Circulating Tumor DNA, Precision Medicine, and Personalized Clinical Management of Cancer. Oliveira, KCS., Ramos, IB., Silva, JMC., et al.[2021]

References

1. China pubmed.ncbi.nlm.nih.gov

[Circulating tumor DNA and targeted therapy in colorectal cancer]. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Circulating tumor DNA (ctDNA) in adjuvant therapy of early stage colon cancer: current status and future perspectives. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Applications of Minimal Residual Disease Assessments by Tumor-Informed and Tumor-Uninformed Circulating Tumor DNA in Colorectal Cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Circulating tumor DNA detection after neoadjuvant treatment and surgery predicts recurrence in patients with early-stage and locally advanced rectal cancer. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Finding Waldo: The Evolving Paradigm of Circulating Tumor DNA (ctDNA)-Guided Minimal Residual Disease (MRD) Assessment in Colorectal Cancer (CRC). [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Personalized Treatment Selection and Disease Monitoring Using Circulating Tumor DNA Profiling in Real-World Cancer Patient Management. [2020]

7. Iran pubmed.ncbi.nlm.nih.gov

Therapeutic impact of determination of RAS mutations in the plasma of patient with colorectal cancer. [2022]

8. Denmark pubmed.ncbi.nlm.nih.gov

Toward liquid biopsies in cancer treatment: application of circulating tumor DNA. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Microarray-based analysis of the BRAF V600 mutations in circulating tumor DNA in melanoma patients. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Current Perspectives on Circulating Tumor DNA, Precision Medicine, and Personalized Clinical Management of Cancer. [2021]