Chemotherapy vs Chemoradiotherapy for Rectal Cancer

(NEO-RT Trial)

Recruiting at 56 trial locations

Overseen By Chris O'Callaghan

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Canadian Cancer Trials Group

Disqualifiers: High-risk biopsy, Pelvic nodes, Prior radiation, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This study is being done to answer the following questions: Is the chance of rectal cancer responding the same if chemotherapy alone is given before limited surgery compared to chemotherapy and radiation therapy given together before limited surgery? If radiation therapy is not given, is quality of life better?

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 for rectal cancer?

Research shows that using capecitabine (Xeloda) or 5-fluorouracil (5-FU) with radiation can effectively reduce the chance of cancer coming back in rectal cancer patients. These drugs, when combined with radiation, have been found to be as effective as each other, and adding oxaliplatin may improve results further. ^{1 2 3 4 5}

Is the combination of chemotherapy and radiation generally safe for treating rectal cancer?

The combination of chemotherapy drugs like capecitabine (Xeloda) or 5-fluorouracil (5-FU) with radiation is generally considered safe for treating rectal cancer, with some patients experiencing side effects like diarrhea and low white blood cell counts. These treatments are well-tolerated and have been shown to be effective in reducing cancer recurrence. ^{1 2 4 5 6}

How does chemoradiotherapy differ from chemotherapy for rectal cancer?

Chemoradiotherapy for rectal cancer combines chemotherapy with radiation therapy, which can enhance the effectiveness of treatment by shrinking tumors before surgery and potentially improving survival rates. This approach often uses oral capecitabine, which is more convenient than the traditional intravenous 5-fluorouracil (5-FU), and has shown similar effectiveness in reducing tumor size and recurrence. ^{1 2 3 7 8}

Research Team

Hagen Kennecke

Principal Investigator

Providence Portland Medical Centre, Portland, OR, USA

Carl Brown

Principal Investigator

St. Paul's Hospital, Vancouver, BC, Canada

Eligibility Criteria

This trial is for adults with mid to low-lying rectal cancer that's suitable for limited surgery, not spread elsewhere (M0), and without certain blood vessel involvement. Patients must be fit for major surgery, able to complete questionnaires in English, French or Spanish, and have no issues with the chemotherapy drugs planned.

Inclusion Criteria

Must be accessible for treatment and follow-up

My cancer is at a stage where it cannot be removed through surgery via the anus or is at stage cT2.

I can complete quality of life surveys in English, French, or Spanish.

Exclusion Criteria

I have had radiation therapy to my pelvic area before.

Patients with visible pelvic sidewall nodes on MRI

My primary cancer lesion has been surgically removed.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either FOLFOX or CAPOX chemotherapy for up to 12 weeks, or chemotherapy with radiation therapy for up to 6 weeks

6-12 weeks

Surgery

After treatment, surgery is performed based on the study doctor's assessment

Follow-up

Participants are monitored for safety and effectiveness after surgery, with visits every 4 months for 2 years, then every 6 months for an additional year, and annually for 2 more years

5 years

Treatment Details

Interventions

• Capecitabine (Anti-metabolites)
• Fluoruracil (Anti-metabolites)
• Leucovorin (Other)
• Oxaliplatin (Alkylating agents)
• Radiation (Radiation)

Trial Overview The study compares two pre-surgery treatments: one group receives only chemotherapy (Fluoruracil, Oxaliplatin, Leucovorin) while the other gets both chemo and radiation therapy followed by limited surgery. The goal is to see if avoiding radiation improves quality of life without affecting treatment response.

Participant Groups

Group I: FOLFOX OR CAPOX Active Control 4 Interventions

FOLFOX= Six cycles of modified FOLFOX consisting of leucovorin, oxaliplatin and bolus fluoruracil (optional), infusional fluorouracil. CAPOX= Capecitabine twice daily for 14 days and Oxaliplatin on day 1

Group II: ChemoRT Active Control 3 Interventions

Standard dose of infusional 5-Fluorouracil/capecitabine and radiation

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

ECOG-ACRIN Cancer Research Group

Collaborator

Trials

122

Recruited

160,000+

Alliance for Clinical Trials in Oncology

Collaborator

Trials

521

Recruited

224,000+

SWOG Cancer Research Network

Collaborator

Trials

403

Recruited

267,000+

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 study involving 67 patients with stage II and III rectal adenocarcinoma, capecitabine was found to be at least as effective as 5-Fluorouracil in adjuvant chemoradiotherapy, with no significant differences in toxicity or overall survival rates.

There was a notable trend towards improved loco-regional recurrence-free survival in patients treated with capecitabine, suggesting it may work better in combination with radiotherapy compared to 5-Fluorouracil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of protracted infusion 5-fluorouracil and capecitabine in adjuvant chemoradiotherapy for rectal cancer. Kurt, M., Ozkan, L., Kurt, E., et al.[2015]

Oral doxifluridine combined with leucovorin is as effective as intravenous 5-fluorouracil (5-FU) in treating rectal cancer post-surgery, with similar rates of recurrence (6.5% for oral vs. 12.1% for IV).

Patients receiving oral doxifluridine reported a significantly better quality of life compared to those on intravenous 5-FU, with more patients scoring 'good' quality of life at 1 and 2 months after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective randomized trial comparing intravenous 5-fluorouracil and oral doxifluridine as postoperative adjuvant treatment for advanced rectal cancer. Min, JS., Kim, NK., Park, JK., et al.[2022]

In a phase II study involving 54 patients with locally advanced rectal cancer, the combination of capecitabine and radiotherapy resulted in a pathologic complete response rate of 18% and a significant downstaging of tumors in 51% of patients, indicating its efficacy as a neoadjuvant treatment.

The treatment was well tolerated, with manageable side effects, and showed a sphincter preservation rate of 67% for tumors located close to the anal verge, making it a convenient alternative to traditional 5-FU infusion methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of capecitabine (Xeloda) and concomitant boost radiotherapy in patients with locally advanced rectal cancer. Krishnan, S., Janjan, NA., Skibber, JM., et al.[2022]

In a study of 86 patients with locally advanced rectal cancer, both neoadjuvant chemotherapy regimens (mFOLFOXIRI and XELOX/SOX) showed similar pathological response rates, with 36.7% for mFOLFOXIRI and 40.5% for XELOX/SOX.

However, mFOLFOXIRI was associated with significantly higher toxicity, as 45% of patients experienced severe neutropenia compared to only 8% in the XELOX/SOX group, indicating that while both regimens are effective, XELOX/SOX may be a safer option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Comparison of mFOLFOXIRI With XELOX/SOX as Neoadjuvant Chemotherapy for Locally Advanced Rectal Cancer. Kodama, H., Terazawa, T., Ishizuka, Y., et al.[2021]

Capecitabine, when used as part of postoperative chemoradiation for stage II-III rectal cancer, is well tolerated by patients, with a low incidence of severe side effects (grade 3 adverse events) such as diarrhea (12%) and proctitis (7%).

The study involved 41 patients and demonstrated that capecitabine is a convenient treatment option, supporting its use in further research for patients who have undergone radical resection for rectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine chemoradiation for rectal cancer after curative surgery. Bajetta, E., Beretta, E., Di Bartolomeo, M., et al.[2015]

In a study of 452 patients with locally advanced rectal cancer, the rate of pathological complete response (pCR) was lower in those treated with oral capecitabine (9.5%) compared to intravenous 5-fluorouracil (20%), although this difference was not statistically significant (P = 0.082).

Despite the lower pCR rate with capecitabine, achieving pCR was found to be a strong independent predictor of survival, highlighting the importance of effective neoadjuvant chemotherapy in improving clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing pathological complete response rate using oral capecitabine versus infusional 5-fluorouracil with preoperative radiotherapy in rectal cancer treatment. Jootun, N., Evans, T., Mak, J., et al.[2018]

Preoperative treatment with radiotherapy and chemoradiation is favored in Europe for stage II/III rectal cancer, aiming to improve surgical outcomes and quality of life, while the U.S. standard of care focuses on postoperative adjuvant chemoradiation.

The oral chemotherapy capecitabine shows promise as a more effective alternative to traditional 5-FU in combination with radiotherapy, potentially enhancing treatment efficacy and patient compliance due to its oral administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving chemoradiotherapy in rectal cancer. Glynne-Jones, R., Debus, J.[2019]

References

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

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

2. Greece pubmed.ncbi.nlm.nih.gov

Comparison of protracted infusion 5-fluorouracil and capecitabine in adjuvant chemoradiotherapy for rectal cancer. [2015]

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

A prospective randomized trial comparing intravenous 5-fluorouracil and oral doxifluridine as postoperative adjuvant treatment for advanced rectal cancer. [2022]

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

Phase II study of capecitabine (Xeloda) and concomitant boost radiotherapy in patients with locally advanced rectal cancer. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

Retrospective Comparison of mFOLFOXIRI With XELOX/SOX as Neoadjuvant Chemotherapy for Locally Advanced Rectal Cancer. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Capecitabine chemoradiation for rectal cancer after curative surgery. [2015]

7. Australia pubmed.ncbi.nlm.nih.gov

Comparing pathological complete response rate using oral capecitabine versus infusional 5-fluorouracil with preoperative radiotherapy in rectal cancer treatment. [2018]

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

Improving chemoradiotherapy in rectal cancer. [2019]