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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a blood test called circulating tumor DNA (ctDNA), which measures tumor DNA in the blood, can help doctors determine the best chemotherapy plan for colorectal cancer patients before surgery. It seeks to establish if patients require more or less intense chemotherapy based on their risk of cancer recurrence. The trial may suit those diagnosed with colorectal cancer that has spread to the abdominal lining and is visible on scans or during surgery. As an unphased trial, it allows patients to contribute to innovative research that could personalize future cancer treatments.

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 prior data suggests that ctDNA testing is safe for colorectal cancer patients?

Research has shown that using a blood test called circulating tumor DNA (ctDNA) to guide treatment holds promise for colorectal cancer care. One study found that ctDNA reduced the need for extra chemotherapy without affecting patients' health, indicating it was well-tolerated and did not lead to more cancer recurrence.

Another study discovered that ctDNA can assess treatment effectiveness and predict cancer recurrence. These findings suggest ctDNA is a safe tool for managing cancer treatment. Overall, ctDNA testing appears to be a safe method for helping doctors select the right treatment for colorectal cancer patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about circulating tumoral DNA (ctDNA)-guided therapy for colorectal cancer because it offers a personalized approach to treatment. Unlike standard chemotherapy, which is typically given for a set duration regardless of individual response, this method uses ctDNA levels to tailor the length of neoadjuvant therapy to each patient. This means treatment can be adjusted in real-time, potentially leading to more effective results and fewer side effects. By closely monitoring ctDNA, doctors can make more informed decisions about the duration and intensity of treatment, aiming for better outcomes with precision.

What evidence suggests that ctDNA-directed therapy is effective for colorectal cancer?

Research has shown that circulating tumor DNA (ctDNA) can be very helpful in treating cancer. One study found that using ctDNA to guide treatment for stage II colon cancer reduced the need for extra chemotherapy without increasing the risk of cancer returning. Other studies have demonstrated that ctDNA can track treatment effectiveness for various cancers, including colorectal cancer. In this trial, participants will join the circulating tumoral DNA-directed neoadjuvant therapy arm, where researchers will measure ctDNA levels to guide the duration of neoadjuvant chemotherapy. This method aims to tailor treatment to each patient, potentially leading to better results. ^{1 2 4 6 7}

Who Is on the Research Team?

Michael White, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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.

My heart function is classified as class 2B or better according to NYHA.

Estimated life-expectancy of > 4 months

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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) 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 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]

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 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) 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12346188/

Circulating Tumor DNA Detects Minimal Residual Disease ... This study aims to investigate ctDNA and its ability to detect minimal residual disease as an adjunct to reassess tumor response in locally ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2200075

Circulating Tumor DNA Analysis Guiding Adjuvant Therapy ... A ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival.

3. nature.com nature.com/articles/s41698-025-00876-y

Circulating tumor DNA to monitor treatment response in ... In this review, we provide a comprehensive, up-to-date summary of ctDNA in monitoring treatment response with a focus on lung, colorectal, and breast cancers.

4. thelancet.com thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00584-X/fulltext

Circulating tumour DNA in predicting and monitoring ... Circulating tumour DNA in predicting and monitoring survival of patients with locally advanced rectal cancer undergoing multimodal treatment.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12346868/

Integrating Circulating Tumor DNA into Clinical Management ... CIRCULATE-Japan: Circulating tumor DNA–guided adaptive platform trials to refine adjuvant therapy for colorectal cancer. Cancer Sci. 2021;112:2915–2920. doi ...

6. nature.com nature.com/articles/s41598-024-80855-8

Assessment of circulating tumor DNA in patients with ... (A) Overview plot showing longitudinal ctDNA status, treatment regimen, and clinical outcomes for patients with stage II–III rectal cancer. (B) ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2210740125000907

Circulating tumor DNA: A new tool to predict recurrence ... Circulating tumor DNA (ctDNA) has emerged as a promising biomarker with diverse applications across different stages of colorectal cancer management.