Radiotherapy for Rectal Cancer

(ROBIN Trial)

Recruiting at 5 trial locations

Overseen By Fabiana Gregucci, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Weill Medical College of Cornell University

Must not be taking: Immunosuppressants, Anticancer, Experimental drugs

Disqualifiers: Recurrent cancer, Unresectable cancer, Transplant, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the impact of short course radiation therapy (scRT) on the immune system in people with rectal cancer. Rectal cancer is common, and radiation is a standard treatment. Participants will receive scRT over five days, with samples collected before, during, and after treatment. This trial suits those diagnosed with localized rectal cancer that can be surgically removed and who have not had prior pelvic radiation or chemotherapy for rectal cancer. As an unphased trial, it offers a unique opportunity to contribute to understanding how scRT affects the immune system, potentially benefiting future patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on systemic immunosuppressive medication or other anticancer or experimental therapies. It's best to discuss your specific medications with the trial team.

What prior data suggests that Short Course Radiation Therapy (scRT) is safe for rectal cancer patients?

Research has shown that short course radiation therapy (scRT) is generally manageable for patients with rectal cancer. One study found that delivering a total of 25 Gy of radiation over five days does not cause more side effects than other treatments. Another analysis indicated that patients who received scRT did not experience more negative effects, confirming the treatment's safety. Additionally, scRT is considered effective and safe for rectal cancer, making it a viable option for those considering clinical trials. Overall, evidence supports the safety of scRT, with few side effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care, which typically involves long courses of chemoradiation for rectal cancer, Short Course Radiation Therapy (scRT) offers a quicker alternative by delivering a total of 25Gy over just five days. This condensed treatment schedule means less time in therapy for patients, potentially leading to a more convenient and less disruptive experience. Researchers are excited about scRT because it promises to maintain effectiveness while reducing the overall treatment burden, allowing patients to proceed to surgery sooner.

What evidence suggests that Short Course Radiation Therapy might be an effective treatment for rectal cancer?

Studies have shown that short course radiation therapy (scRT), which participants in this trial will receive, effectively treats rectal cancer. Previous patients achieved high rates of complete tumor removal, and in some cases, no cancer was found after treatment. Research indicates that scRT also results in low rates of cancer recurrence in the treated area. Known for causing fewer side effects than longer radiation treatments, scRT is also cost-effective and provides good long-term outcomes for patients. Overall, scRT is a proven treatment option for rectal cancer with promising results. ^{1 6 7 8 9}

Who Is on the Research Team?

Silvia Formenti, M.D.

Principal Investigator

Weill Medical College of Cornell University

Encouse Golden, M.D., Ph.D.

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

Adults over 18 with a specific type of rectal cancer that hasn't spread far or been treated yet. They must be in good health, not pregnant, and willing to use birth control. People can't join if they've had certain treatments before, have more advanced cancer, are on strong immune system drugs, or have other serious health issues.

Inclusion Criteria

My diagnosis is rectal adenocarcinoma.

I am not on antibiotics for an infection.

I am fully active or can carry out light work.

Exclusion Criteria

I have had radiation therapy to my pelvic area before.

Patients with any other concurrent medical or psychiatric condition or disease which, in the investigator's judgment would make them inappropriate candidates for entry into this study

My rectal cancer has come back.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Participants receive short course radiation therapy (scRT) of 25Gy over 5 days for localized rectal cancer

1 week

5 visits (in-person)

Surgery

Surgical procedure to assess pathological response and collect biospecimens

Week 6

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Short Course Radiation Therapy (scRT)
• Total Mesenteric Excision (TME)

Trial Overview The trial is testing how standard short course radiation therapy affects the immune response in rectal cancer patients who will also undergo surgery called Total Mesenteric Excision. It's for those whose cancer hasn't spread too much and aims to understand treatment effects better.

How Is the Trial Designed?

Group I: Single cohort Experimental Treatment 2 Interventions

Eligible patients will receive short course radiation therapy (scRT) of 25Gy over 5 days (fractions) for their localized rectal cancer. Research bloods stool and tissue will be collected at three time points: Baseline, end of radiation therapy and at surgery.

Short Course Radiation Therapy (scRT) is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Short Course Radiation Therapy for:

• Rectal cancer
• Locally advanced rectal cancer

Approved in United States as Short Course Radiation Therapy for:

• Rectal cancer
• Locally advanced rectal cancer

Approved in Canada as Short Course Radiation Therapy for:

• Rectal cancer
• Locally advanced rectal cancer

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 3469 rectal cancer patients who underwent preoperative short-course radiotherapy (SCRT), the majority (76%) had surgery within 7 days of treatment, but the timing did not affect postoperative outcomes such as mortality or length of hospital stay.

The findings indicate that the interval between SCRT and surgery does not significantly influence 30-day postoperative mortality or 1-year survival, providing important real-world evidence that can help guide treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time to Surgery Following Short-Course Radiotherapy in Rectal Cancer and its Impact on Postoperative Outcomes. A Population-Based Study Across the English National Health Service, 2009-2014. Levick, BA., Gilbert, AJ., Spencer, KL., et al.[2021]

A meta-analysis of 11 studies involving 1984 patients found that preoperative short-course radiotherapy (SCRT) is as effective as long-course radiochemotherapy (LCRT) for long-term survival in locally advanced rectal cancer, with no significant differences in overall survival, disease-free survival, or local recurrence rates.

SCRT may be a preferable option in situations with long waiting lists or limited medical resources, as it provides similar efficacy to LCRT while potentially reducing treatment time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer: Meta-analysis with trial sequential analysis of long-term survival data. Wang, X., Zheng, B., Lu, X., et al.[2019]

In a study of 57 patients with locally advanced rectal cancer, neoadjuvant short-course radiation therapy (SCRT) showed similar effectiveness in tumor response and safety outcomes whether surgery was performed immediately or after a delay, indicating SCRT is well-tolerated regardless of timing.

Patients who had surgery delayed after SCRT experienced significantly higher rates of nodal downstaging (64.7% vs. 18.2%), suggesting that delaying surgery may enhance certain aspects of tumor response without increasing toxicity or complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathologic Response and Postoperative Complications After Short-course Radiation Therapy and Chemotherapy for Patients With Rectal Adenocarcinoma. Avila, S., Chang, GJ., Dasari, NA., et al.[2021]

In a study of 1606 rectal cancer patients, the overall local recurrence rate after potentially curative surgery was only 4.0%, suggesting that the risk of recurrence is low.

The findings indicate that routine preoperative short-course radiotherapy may not be necessary for all patients, as selective use could be more beneficial, especially when local recurrence rates are already low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low rates of local recurrence after surgical resection of rectal cancer suggest a selective policy for preoperative radiotherapy. Senapati, A., O'Leary, DP., Flashman, KG., et al.[2012]

Preoperative short-course radiation therapy (SCRT) followed by immediate surgery has shown high efficacy in treating rectal cancer, with 5-year locoregional control at 95.9%, disease-free survival at 76.4%, and overall survival at 84.6% based on a study of 202 patients with clinical stage I-III disease.

The treatment was found to be safe, with a late severe toxicity rate of only 11.4%, suggesting that SCRT could be a viable option for rectal cancer patients in the U.S., especially as national guidelines begin to support its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative short-course radiation therapy for rectal cancer provides excellent disease control and toxicity: Results from a single US institution. Roy, A., Mahasittiwat, P., Weiner, AA., et al.[2022]

In a clinical trial involving 19 patients with nonmetastatic rectal adenocarcinoma, short-course radiation therapy (SCRT) followed by chemotherapy achieved a high clinical complete response (cCR) rate of 68% at one year, indicating its efficacy as a nonoperative treatment option.

Patients who achieved cCR had significantly better 2-year disease-free survival (93% vs 67%) and overall survival (100% vs 67%) compared to those who did not, while maintaining intact anorectal function and experiencing no severe late effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonoperative Rectal Cancer Management With Short-Course Radiation Followed by Chemotherapy: A Nonrandomized Control Trial. Kim, H., Pedersen, K., Olsen, JR., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11557790/

Long-term outcomes and prognostic factors of short-course ... SCRT is an effective treatment in patients with rectal cancer and provides good outcomes with very low rates of toxicity profile.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0936655524004187

Early Outcomes of Preoperative Short Course ... Patients who underwent surgery achieve a high R0 resection and pCR rates. Early data suggest low rates of locoregional recurrence.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12078407/

long-term results of a randomized controlled trial Short-course radiotherapy (SCRT) and long-course radiotherapy (LCRT) are the primary neoadjuvant radiotherapy schedules for locally advanced rectal cancer.

4. eymj.org eymj.org/pdf/10.3349/ymj.2023.0042

Short-Term Outcomes and Cost-Effectiveness between ... In addition, SCRT showed significant reduc- tion in the total cost of care and distinguished cost-effectiveness compared to LCRT. Key Words: ...

5. cancernetwork.com cancernetwork.com/view/short-course-radiation-may-be-feasible-in-older-rectal-cancer-population

Short-Course Radiation May Be Feasible in Older Rectal ... The study treatment produced a median relapse-free survival (RFS) of 31.5 months (95% CI, 16.0-46.9), a median overall survival (OS) of 40.5 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10310334/

Short-course radiotherapy for rectal cancer - PubMed Central Short-course radiotherapy (SCRT), which allows the delivery of 25 Gy in five daily fractions, has emerged as an attractive strategy for rectal cancer treatment ...

7. thegreenjournal.com thegreenjournal.com/article/S0167-8140(25)05198-9/fulltext

A multicenter analysis of early outcomes and toxicity Short-course radiotherapy versus long-course chemoradiotherapy in total neoadjuvant therapy of rectal cancer – A multicenter analysis of early outcomes and ...

8. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00286-4/fulltext?rss=yes

Total neoadjuvant treatment with short-course radiotherapy ... We aimed to compare the efficacy and safety of short-course radiotherapy followed by 6 cycles of capecitabine plus oxaliplatin chemotherapy with ...

9. practicalradonc.org practicalradonc.org/article/S1879-8500(16)30162-X/abstract

Preoperative short-course radiation therapy for rectal ... Median follow-up was 6.5 years (range, 2-29.2). Five-year disease outcomes were 95.9% ± 1.5% for LC, 76.4% ± 3.1% for DFS, and 84.6% ± 2.6% for OS. For patients ...