Chemotherapy vs Chemoradiotherapy for Rectal Cancer

(NEO-RT Trial)

Recruiting at 91 trial locations

Overseen By Chris O'Callaghan

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Canadian Cancer Trials Group

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

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-12 weeks

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to treat rectal cancer before surgery. It compares chemotherapy alone to chemotherapy with radiation to determine which approach enhances cancer response and improves quality of life. Participants will receive either a combination of chemotherapy drugs like Capecitabine (Xeloda) and Oxaliplatin or chemotherapy with radiation. Suitable candidates have rectal cancer that has not spread and are medically fit for surgery. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both FOLFOX and CAPOX treatments are generally well-tolerated by patients with colorectal cancer. Studies comparing these treatments have found CAPOX to be safer than the combination of 5-FU (fluorouracil) and oxaliplatin, while maintaining equal effectiveness. One study suggested that 3 months of treatment with either FOLFOX or CAPOX is as effective as 6 months, with fewer side effects.

For the ChemoRT (chemoradiotherapy) approach, research indicates that using capecitabine with radiation can safely improve outcomes for patients with locally advanced rectal cancer, including better tumor response and more successful surgeries. Both treatment types have demonstrated good long-term survival rates in patients.

Overall, the treatments in this trial have been tested in other studies and have a strong safety record. However, individual experiences may vary. Always discuss potential risks and benefits with a healthcare provider before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for rectal cancer because they explore different combinations of chemotherapy and radiation to optimize patient outcomes. The FOLFOX or CAPOX regimens are unique because they combine oxaliplatin with either 5-fluorouracil or capecitabine, potentially offering a more effective chemotherapy approach. The ChemoRT arm, which pairs standard doses of infusional 5-Fluorouracil or capecitabine with radiation, aims to enhance the cancer-killing effects of radiation. These approaches could provide more targeted and efficient treatment options compared to the existing standard care, which typically involves surgery followed by adjuvant chemoradiotherapy.

What evidence suggests that this trial's treatments could be effective for rectal cancer?

Research has shown that both FOLFOX and CAPOX treatments, studied in this trial, effectively manage rectal cancer. One study found that about 80% of patients treated with these methods did not experience cancer recurrence within five years.

For the ChemoRT treatment arm in this trial, which combines chemotherapy with radiation, studies indicate it provides high survival rates and helps maintain the function of muscles that control bowel movements. Patients generally tolerated chemoradiotherapy with capecitabine, a type of oral chemotherapy included in this arm, experiencing fewer severe side effects. ^{1 4 6 7 8}

Who Is on the Research Team?

Hagen Kennecke

Principal Investigator

Providence Portland Medical Centre, Portland, OR, USA

Carl Brown

Principal Investigator

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

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Fluoruracil
• Leucovorin
• Oxaliplatin
• 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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6831214/

Capecitabine versus 5-fluorouracil in neoadjuvant ... Our study showed that capecitabine-based neoadjuvant CRT benefit the pCR of rectal cancer patients, which means more selected patients who get a cCR after ...

2. por-journal.com por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2022.1610722/full

Clinical benefits of oral capecitabine over intravenous 5 ... The study confirms advantages of neoadjuvant chemoradiotherapy with oral capecitabine for rectal tumours, such as more favourable side effect profile and ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.3_suppl.92

Neoadjuvant chemoradiotherapy with capecitabine in ... Conclusions: CRT with capecitabine provides high rates of survival and sphinter preservation with excellent tolerance. Patients with adverse ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2786689

Postoperative Chemoradiotherapy With Capecitabine and ... In this randomized clinical trial of 602 adults, the addition of oxaliplatin to capecitabine-based postoperative CRT did not significantly improve disease-free ...

5. redjournal.org redjournal.org/article/S0360-3016(09)00517-3/fulltext

Preoperative Capecitabine and Pelvic Radiation in Locally ... At 3 years, there was no significant difference in the local control rate (93% for capecitabine and 92% for 5-FU and leucovorin), relapse-free rate (74% for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5116508/

Effect of Neoadjuvant Chemoradiotherapy with ... This meta-analysis compared the efficacy and safety of capecitabine plus radiation with 5-FU plus RT as neoadjuvant treatment in LARC. In the light of its ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03428529?term=AREA%5BBasicSearch%5D(capecitabine)&rank=3

Capecitabine Versus Bolus 5-Fu Associated to ... A randomized two-arm study comparing preoperative CRT using oral capecitabine versus bolus 5-FU/LV concomitant to external beam radiation (50.5 Gy/28 ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2303269

Preoperative Treatment of Locally Advanced Rectal Cancer Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy ...