What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as Radiation Therapy combined with Chemotherapy using Fluorouracil, Leucovorin, and Oxaliplatin, have several known side effects. Fluorouracil can cause side effects like diarrhea, nausea, vomiting, and neutropenia (low white blood cell count). Leucovorin, while generally used to enhance the efficacy of Fluorouracil, can also contribute to gastrointestinal side effects. Oxaliplatin is associated with neurotoxicity, which can manifest as peripheral neuropathy (tingling or numbness in the hands and feet), as well as neutropenia and nausea. Radiation therapy itself can cause skin irritation, fatigue, and gastrointestinal symptoms such as diarrhea. When these treatments are combined, the side effects can be more pronounced, requiring careful management and dose adjustments.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of colorectal cancer that are similar to those being studied in the trial involving radiation therapy with chemotherapy. Fluorouracil (5-FU) is a cornerstone chemotherapeutic agent that enhances the sensitivity of tumor cells to radiation. Leucovorin is often used in combination with fluorouracil to enhance its efficacy and protect normal cells. Oxaliplatin, another FDA-approved drug, is used in combination regimens such as FOLFOX (fluorouracil, leucovorin, and oxaliplatin) to inhibit tumor cell growth. These drugs have been integral in the treatment of colorectal cancer, particularly in adjuvant and neoadjuvant settings.

What other types of research exist?

Promising novel alternatives for Colorectal Cancer treatment in 2024 include immunotherapy agents such as immune checkpoint inhibitors (e.g., pembrolizumab, nivolumab) for tumors with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). Targeted therapies like BRAF inhibitors (e.g., encorafenib) combined with EGFR inhibitors (e.g., cetuximab) for BRAF V600E-mutant tumors are also promising. Additionally, novel combination therapies involving newer agents like bevacizumab (an anti-VEGF antibody) with capecitabine or FOLFOX have shown potential. These alternatives may offer improved efficacy and reduced toxicity compared to traditional chemoradiotherapy.

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Anti-metabolites

Radiation Therapy + Fluorouracil for Rectal Cancer

Phase 2

Waitlist Available

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

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

Must have

Patients must have histologically confirmed invasive adenocarcinoma of the rectum with the distal border of the tumor within 12 cm from the anal verge as measured on rigid proctoscopic exam

Patients must have an Eastern Cooperative Oncology Group (ECOG) Status of 0 or 1, or comparable Karnofsky performance status

Must not have

History of allergy and/or hypersensitivity to 5-fluorouracil (fluorouracil), leucovorin (leucovorin calcium), and/or oxaliplatin

History of psychiatric conditions or diminished capacity that could compromise the giving of informed consent, or interfere with study compliance

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if combining radiation therapy with chemotherapy can shrink tumors in patients with stage II or III rectal cancer. The treatment aims to make tumors smaller and easier to remove while protecting normal cells. The study will also look at the timing of treatments and their effects on surgery and recovery.

Who is the study for?

This trial is for adults with stage II or III rectal cancer, who can perform daily activities on their own or need some help (ECOG 0-1). They must have a tumor within 12 cm of the anal verge and no history of certain diseases like inflammatory bowel disease, familial adenomatous polyposis, or recent heart issues. Prior pelvic radiation treatments disqualify them. Adequate organ function and agreement to use birth control are required.

What is being tested?

The study tests how well radiation therapy combined with fluorouracil chemotherapy works compared to adding more drugs (oxaliplatin and leucovorin) before surgery. The goal is to shrink tumors and spare healthy tissue. It includes DNA analysis and other lab tests to see how patients respond.

What are the potential side effects?

Possible side effects include skin irritation from radiation, fatigue, nausea, mouth sores from fluorouracil; nerve damage like tingling or numbness from oxaliplatin; allergic reactions; blood count changes leading to infection risk; liver enzyme alterations.

Eligibility Criteria

Inclusion Criteria

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

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My rectal cancer is confirmed and is within 12 cm from the anal opening.

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I am fully active or able to carry out light work.

Exclusion Criteria

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

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I am allergic to 5-fluorouracil, leucovorin, or oxaliplatin.

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I do not have any mental health conditions that would affect my ability to follow study rules.

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My cancer has spread to other parts of my body.

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I have trouble taking or absorbing pills.

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My rectal cancer has come back in the same area.

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I have a serious heart condition or had a heart attack in the last 6 months.

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I have had radiation therapy to my pelvis before.

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I have a history of inflammatory bowel disease.

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I have a history of Familial Adenomatous Polyposis.

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I have no history of uncontrolled seizures or major brain disorders.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

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

Group I: Group 4 (chemotherapy, FOLFOX, conventional surgery)Experimental Treatment9 Interventions

All patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil IV continuously over 24 hours 7 days a week for 6 weeks. Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy as in group II. Treatment repeats every 14 days for 6 courses. After the last week of post- radiation chemotherapy, patients undergo standard surgical resection. Patients then receive 3 additional courses of FOLFOX-6 chemotherapy or other chemotherapy off study as directed by the physician.

Group II: Group 3 (chemotherapy, FOLFOX, conventional surgery)Experimental Treatment9 Interventions

All patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil IV continuously over 24 hours 7 days a week for 6 weeks. Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy as in group II. Treatment repeats every 14 days for 4 courses. After the last week of post-radiation chemotherapy, patients undergo standard surgical resection.

Group III: Group 2 (Closed to Enrollment)Experimental Treatment9 Interventions

All patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil IV continuously over 24 hours 7 days a week for 6 weeks. Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1-2. Treatment repeats every 14 days for 2 courses. After the last week of post-radiation chemotherapy, patients undergo standard surgical resection.

Group IV: Group 1 (Closed to Enrollment)Experimental Treatment7 Interventions

All patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil intravenously continuously over 24 hours 7 days a week for 6 weeks. Patients undergo standard surgical resection after completion of chemoradiation therapy..

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

DNA analysis

2007

Completed Phase 2

~6450

leucovorin calcium

1999

Completed Phase 3

~8620

fluorouracil

1994

Completed Phase 3

~8440

polymerase chain reaction

2006

Completed Phase 2

~1700

oxaliplatin

2002

Completed Phase 3

~6370

radiation therapy

1994

Completed Phase 3

~13390

conventional surgery

1994

Completed Phase 3

~13900

0 / 12Eligibility 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

Radiation therapy uses high-energy x-rays to kill tumor cells by damaging their DNA, which is crucial for shrinking tumors before surgery. Fluorouracil (5-FU) is a chemotherapy drug that inhibits thymidylate synthase, disrupting DNA synthesis and making tumor cells more sensitive to radiation. Leucovorin enhances the efficacy of fluorouracil by stabilizing the binding of fluorouracil to thymidylate synthase, and it also helps protect normal cells from the side effects of chemotherapy. Oxaliplatin is another chemotherapy agent that forms cross-links in DNA, preventing tumor cells from growing and dividing. These treatments are important for colorectal cancer patients as they work synergistically to reduce tumor size, improve surgical outcomes, and increase the chances of disease-free survival.