Radiation Therapy + Fluorouracil for Rectal Cancer

Recruiting at 14 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: 5-fluorouracil, leucovorin, oxaliplatin

Disqualifiers: Metastatic disease, Inflammatory Bowel Disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

248 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Radiation Therapy + Fluorouracil for Rectal Cancer?

Research shows that combining 5-fluorouracil (5-FU) with radiation therapy is more effective than radiation alone for treating localized rectal cancer, as it reduces local relapse rates and has a favorable safety profile. ^{1 2 3 4 5}

Is the combination of radiation therapy and 5-fluorouracil safe for humans?

The combination of radiation therapy and 5-fluorouracil (5-FU) can cause side effects like diarrhea and, in rare cases, heart problems. However, these treatments have been used in various studies, and while side effects exist, they are generally considered manageable. ^{2 6 7 8 9}

How is the treatment of Radiation Therapy + Fluorouracil for rectal cancer different from other treatments?

This treatment combines radiation therapy with fluorouracil (5-FU) and oxaliplatin, which may enhance the effectiveness of reducing tumor size before surgery compared to using 5-FU and radiation alone. The addition of oxaliplatin is being investigated for potentially better outcomes, although it is not yet a standard part of treatment. ^{2 3 5 10 11}

Research Team

Julio Garcia-Aguilar, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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.

Inclusion Criteria

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

I can be part of the study if MRI can stage my condition due to a high-grade obstruction.

I have hereditary non-polyposis colorectal cancer and meet other study requirements.

Exclusion Criteria

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

Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.0 times institutional upper limit of normal (ULN)

Serum creatinine =< 1.5 times ULN

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Participants undergo radiation therapy once daily 5 days a week for 5 weeks and receive fluorouracil intravenously continuously over 24 hours 7 days a week for 6 weeks

6 weeks

Chemotherapy

Beginning 4 weeks after completion of chemoradiation therapy, participants receive modified FOLFOX-6 chemotherapy. Treatment repeats every 14 days for 2 to 6 courses depending on the group

4-12 weeks

Surgery

Participants undergo standard surgical resection after completion of chemoradiation and chemotherapy

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Conventional Surgery
• Fluorouracil
• Leucovorin Calcium
• Oxaliplatin
• Radiation Therapy

Trial Overview 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.

Participant Groups

Group I: Group 4 (chemotherapy, FOLFOX, conventional surgery) Experimental Treatment 9 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 Treatment 9 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 Treatment 9 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 Treatment 7 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..

Fluorouracil is already approved in United States, European Union, Canada for the following indications:

Approved in United States as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Skin cancer

Approved in European Union as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Canada as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Neoadjuvant chemoradiation, particularly with fluorouracil (5-FU) plus radiation, is now the preferred treatment for stage II/III rectal cancer, showing lower local relapse rates and better safety compared to postoperative treatments.

Capecitabine (Xeloda) plus radiation has been found to be as effective as 5-FU plus radiation, making it a viable alternative, while combinations with oxaliplatin or irinotecan show promise for improved outcomes and warrant further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiation for rectal cancer: is more better? Patel, A., Puthillath, A., Yang, G., et al.[2018]

In a phase 2 trial involving 63 anal cancer patients, dose-painted intensity modulated radiation therapy (DP-IMRT) did not significantly reduce the overall rate of grade 2+ gastrointestinal and genitourinary adverse events compared to conventional treatment, but it did show a notable reduction in grade 3+ gastrointestinal (21% vs. 36%) and dermatologic (23% vs. 49%) toxicities.

DP-IMRT was found to be feasible, but a high rate of pretreatment planning revisions (81%) highlights the need for careful real-time quality assurance in radiation therapy to ensure patient safety and treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. Kachnic, LA., Winter, K., Myerson, RJ., et al.[2022]

The Phase I study determined that the maximal tolerated dose of capecitabine combined with standard radiotherapy for rectal cancer is 1600 mg/m²/day, which is important for future treatment protocols.

Dose-limiting toxicities were observed at lower doses, including Grade 3 diarrhea and skin toxicity, indicating that while capecitabine can be effective, careful monitoring for side effects is necessary during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter dose-finding study of concurrent capecitabine and radiotherapy as adjuvant treatment for operable rectal cancer. Souglakos, J., Androulakis, N., Mavroudis, D., et al.[2019]

A series of clinical trials initiated by the Gastrointestinal Tumor Study Group in the 1970s explored the effectiveness of radiation therapy combined with chemotherapy for treating pancreatic, rectal, and gastric adenocarcinomas, which were previously thought to be resistant to radiation.

The trials included various treatment protocols, such as comparing high-dose radiation with chemotherapy to lower doses, and consistently used 5-fluorouracil as a chemotherapeutic agent, indicating a systematic approach to improving outcomes for patients with locally unresectable tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An organized multi-institutional interdisciplinary evaluation of role of radiation therapy alone or combined with chemotherapy in treatment of adenocarcinoma of the gastrointestinal tract. Douglass, HO., Stablein, DM., Thomas, PR.[2007]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Chemotherapy of colorectal cancer. [2013]

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

A study of radiotherapy modalities combined with continuous 5-FU infusion for locally advanced gastrointestinal malignancies. [2013]

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

Neoadjuvant chemoradiation for rectal cancer: is more better? [2018]

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

5-Fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development. [2023]

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

Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048). [2023]

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

Acute diarrhea during adjuvant therapy for rectal cancer: a detailed analysis from a randomized intergroup trial. [2019]

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

RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Biweekly oxaliplatin, raltitrexed, 5-fluorouracil and folinic acid combination chemotherapy during preoperative radiation therapy for locally advanced rectal cancer: a phase I-II study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Safe administration of S-1 after 5-fluorouracil-induced cardiotoxicity in a patient with colorectal cancer. [2020]

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

Multicenter dose-finding study of concurrent capecitabine and radiotherapy as adjuvant treatment for operable rectal cancer. [2019]

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

An organized multi-institutional interdisciplinary evaluation of role of radiation therapy alone or combined with chemotherapy in treatment of adenocarcinoma of the gastrointestinal tract. [2007]