What side effects are associated with this type of intervention?

Common treatments for colon cancer, such as fluoropyrimidine-based chemotherapy and oxaliplatin, are associated with several side effects. Fluoropyrimidines can cause gastrointestinal issues like nausea, vomiting, diarrhea, and mucositis, as well as hematologic toxicities such as neutropenia and anemia. Oxaliplatin is notably associated with peripheral neuropathy, which can manifest as tingling, numbness, and pain in the extremities, potentially impacting quality of life. Both treatments can also lead to fatigue and increased risk of infections due to immunosuppression.

What prior FDA approvals exist?

The FDA has approved several chemotherapy agents for the treatment of colon cancer, including fluoropyrimidines (such as 5-fluorouracil and capecitabine), oxaliplatin, and irinotecan. These agents are often used in combination regimens like FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) and FOLFIRI (5-fluorouracil, leucovorin, and irinotecan). Additionally, targeted therapies such as bevacizumab (an anti-VEGF antibody) and cetuximab (an anti-EGFR antibody) have been approved for use in combination with chemotherapy. The trial evaluating chemotherapy regimens guided by ctDNA biomarkers aims to personalize treatment based on the presence of circulating tumor DNA, potentially improving outcomes by tailoring therapy to the molecular profile of the cancer.

What other types of research exist?

Promising novel alternatives to chemotherapy for colon cancer patients in 2024 include immunotherapy and targeted therapies. Immunotherapy options, such as immune checkpoint inhibitors (e.g., pembrolizumab), are being explored, especially for patients with specific genetic markers like dMMR or high TMB. Targeted therapies, including those aimed at specific mutations or pathways involved in colon cancer, are also under investigation. These alternatives may offer personalized treatment options based on the patient's genetic profile and tumor characteristics.

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Chemotherapy Tailored by ctDNA Status for Colon Cancer (CIRCULATE-US Trial)

Phase 2 & 3

Recruiting

Research Sponsored by NRG Oncology

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

ECOG performance status of 0 or 1

Histologically/pathologically confirmed colon adenocarcinoma (T1-3, N1/N1c) with R0 resection

Must not have

Colon cancer histology other than adenocarcinoma

Pathologic, clinical, or radiologic overt evidence of metastatic disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up time from randomization to death, a maximum of 5 years.

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if a blood test for cancer DNA can help decide if colon cancer patients need more treatment after surgery. The test looks for cancer DNA in the blood to predict if the cancer might come back and to guide further treatment.

Who is the study for?

This trial is for adults with colon adenocarcinoma who've had surgery, no metastatic disease, and a good performance status. They must be able to take chemo drugs like 5FU and oxaliplatin, have stable HIV if present, not be pregnant or breastfeeding, and agree to ctDNA testing using the Signatera test.

What is being tested?

The study tests different chemotherapy durations (3-6 months) using mFOLFOX6 or CAPOX based on circulating tumor DNA presence after colon cancer surgery. It aims to tailor post-surgery chemo treatment more effectively.

What are the potential side effects?

Chemotherapy side effects can include nausea, vomiting, diarrhea, fatigue, risk of infection due to low blood cell counts, neuropathy (nerve problems), and liver function changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or can carry out light work.

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My colon cancer was confirmed by a lab test and has been fully removed by surgery.

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My tumor is located more than 12 cm from the anal opening or above the peritoneal reflection.

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My tumor was completely removed in one piece.

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My tumor is not affected by certain genetic instabilities.

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I can receive treatments like 5FU, LV, oxaliplatin, and irinotecan.

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I can provide tissue samples from my surgery for further testing.

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I am fully active or can carry out light work.

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My blood, liver, and kidney tests are normal.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My colon cancer is not adenocarcinoma.

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My cancer has spread to other parts of my body.

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My cancer has caused a hole in my intestine.

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I have had colon cancer before.

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I have had a bone marrow or organ transplant.

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I have had chemotherapy, targeted therapy, immunotherapy, or radiation for colorectal cancer.

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I have not had any other cancer besides this one in the last 5 years.

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I have cancer in both my rectum and colon at the same time.

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My heart condition limits my physical activity.

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I have moderate to severe numbness, tingling, or muscle weakness.

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I have seizures that medication does not control.

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I am currently on medication for a long-term infection.

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I have a confirmed DPD deficiency.

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I have Gilbert's Syndrome or a specific genetic condition (UGT1A1*28).

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ time from randomization to death, a maximum of 5 years.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~time from randomization to death, a maximum of 5 years.

This trial's timeline: 3 weeks for screening, Varies for treatment, and time from randomization to death, a maximum of 5 years. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Disease-Free Survival (DFS)

ctDNA positive status (TTPos)

Secondary study objectives

Baseline post-surgery ctDNA positivity rate

Compliance with adjuvant chemotherapy

Overall Survival (OS)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Group I: Cohort B - Arm 4 (ctDNA+ve)Experimental Treatment2 Interventions

Oxaliplatin 85 mg/m2 IV + Leucovorin 400mg/m2 IV + Irinotecan 150 mg/m2 IV continuous infusion (30-90 minutes) + 5-Fluorouracil (5-FU) 2400mg/m2 IV continuous infusion over 46-48 hours (total dose) Day1 every 2 weeks for 12 cycles

Group II: Cohort A - Arm 2 (ctDNA-ve)Experimental Treatment1 Intervention

Serial ctDNA monitoring no treatment

Group III: Cohort A - Arm 1 (ctDNA-ve)Active Control3 Interventions

Oxaliplatin 85 mg/m2 IV + Leucovorin 400mg/m2 IV + 5-Fluorouracil (5-FU) 400mg/m2 bolus + 5-Fluorouracil (5-FU) 2400mg/m2 IV continuous infusion over 46-48 hours (total dose) Day1 every 2 weeks for 6-12 cycles OR Oxaliplatin 130 mg/m2 IV Day 1 every 3 weeks + Capecitabine 1000 mg/m2 BID by mouth days 1-14 every 3 weeks for 4 cycles

Group IV: Cohort B - Arm 3 (ctDNA+ve)Active Control3 Interventions

Oxaliplatin 85 mg/m2 IV + Leucovorin 400mg/m2 IV + 5-Fluorouracil (5-FU) 400mg/m2 bolus + 5-Fluorouracil (5-FU) 2400mg/m2 IV continuous infusion over 46-48 hours (total dose) Day1 every 2 weeks for 12 cycles OR Oxaliplatin 130 mg/m2 IV Day 1 every 3 weeks + Capecitabine 1000 mg/m2 BID by mouth days 1-14 every 3 weeks for 8 cycles

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

mFOLFIRINOX

2013

Completed Phase 2

~90

0 / 23Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for colon cancer include chemotherapy regimens such as fluoropyrimidines (e.g., 5-fluorouracil), oxaliplatin, and irinotecan. Fluoropyrimidines work by inhibiting thymidylate synthase, an enzyme crucial for DNA synthesis, thereby preventing cancer cell replication. Oxaliplatin forms platinum-DNA adducts, causing DNA crosslinking and apoptosis. Irinotecan inhibits topoisomerase I, an enzyme involved in DNA replication, leading to DNA damage and cell death. The use of ctDNA biomarkers in guiding chemotherapy regimens is significant as it allows for personalized treatment plans, potentially improving efficacy and reducing unnecessary toxicity. This approach is particularly important for colon cancer patients, as it can help identify those who are more likely to benefit from specific chemotherapeutic agents, thereby optimizing treatment outcomes.

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