Ultra-fractionated Radiotherapy for Rectal Cancer

Overseen By Sarah Neufeld

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Metastatic disease, Prior pelvic RT, Uncontrolled illness, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

27 Participants Needed

Trial Summary

What is the purpose of this trial?

The rationale of this clinical trial is to assess the feasibility of selective non-operative management for locally advanced rectal cancer using dose-escalated ultra-fractionated short course radiation therapy interdigitated with chemotherapy. We believe delivering short course radiotherapy over a prolonged interval, at escalated doses and with concurrent chemotherapy may be feasible and allow for improved clinical response.

Do I need to stop my current medications for the trial?

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 Ultra-fractionated Radiotherapy for Rectal Cancer?

Research shows that short-course radiation therapy can improve local control of rectal cancer, and similar hypofractionated treatments have been effective in prostate cancer, suggesting potential benefits for rectal cancer as well. ^{1 2 3 4 5}

Is ultra-fractionated radiotherapy generally safe for humans?

Ultra-fractionated radiotherapy, also known as ultra-hypofractionated radiotherapy, has been studied in prostate and breast cancer treatments and is generally considered safe. Studies have shown that it has acceptable levels of side effects, both in the short term and long term, making it a viable option for patients. ^{6 7 8 9 10}

How is Ultra-fractionated Radiotherapy for Rectal Cancer different from other treatments?

Ultra-fractionated Radiotherapy for Rectal Cancer is unique because it involves delivering radiation in several small doses multiple times a day, which is different from the traditional approach of fewer, larger doses. This method aims to improve treatment effectiveness and potentially reduce side effects by spreading out the radiation exposure. ^{1 3 4 11 12}

Research Team

Nina Sanford, MD

Principal Investigator

UT SOUTHWESTERN medical CENTRE

Eligibility Criteria

Adults with locally advanced rectal cancer who haven't had previous treatment for it. They must have good organ and bone marrow function, no distant nodal or metastatic disease, and a stable health condition without severe psychiatric illness. Participants need to agree to use contraception during the trial.

Inclusion Criteria

Willing and able to provide written informed consent

My cancer is at a stage where it has grown into surrounding tissues or spread to nearby lymph nodes.

T Bili ≤ 1.5 x upper limit of normal (ULN);

Exclusion Criteria

Psychiatric illness/social situations that would limit consenting and compliance with study requirements.

I do not have any severe illnesses like heart failure or mental health issues that would stop me from following the study's requirements.

Participants who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive dose-escalated hypofractionated adaptive radiotherapy

Up to 60 days

Chemotherapy

Participants receive FOLFOX or CAPOX chemotherapy interdigitated with radiotherapy

Concurrent with radiation

Follow-up

Participants are monitored for safety, effectiveness, and disease progression

1 year

Treatment Details

Interventions

• Ultrafractionated Radiotherapy for Rectal Cancer

Trial Overview The trial is testing a new approach called ultra-fractionated radiotherapy combined with chemotherapy in patients with rectal cancer. The goal is to see if this method allows for better control of the disease without surgery.

Participant Groups

Group I: Phase I Dose Cohorts Experimental Treatment 1 Intervention

DOSE LEVEL 1 : 30 Gy (tumor)/ 25 Gy (pelvis) DOSE LEVEL 2 : 35 Gy (tumor)/ 25 Gy (pelvis) DOSE LEVEL 3 : 40 Gy (tumor)/ 25 Gy (pelvis)

Ultrafractionated Radiotherapy for Rectal Cancer is already approved in United States, China, European Union for the following indications:

Approved in United States as Ultra-fractionated Radiotherapy for:

• Locally Advanced Rectal Cancer

Approved in China as Hypofractionated Radiotherapy for:

• Locally Recurrent Rectal Cancer

Approved in European Union as Ultra-fractionated Radiotherapy for:

• Rectal Cancer

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Findings from Research

Short-course radiation followed by early surgery provides similar oncologic outcomes as long-course chemoradiation for patients with locally advanced rectal cancer, making it a viable treatment option.

Delaying surgery after short-course radiation can reduce post-operative complications and allows for the administration of neoadjuvant systemic therapy, which may enhance tumor response and lower the risk of distant relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Short-Course Radiation Therapy for Rectal Cancer: Trends and Controversies. Narang, AK., Meyer, J.[2019]

The study identified a radiation therapy schedule of 42.6 Gy in 10 fractions as the shortest regimen with acceptable toxicity for patients undergoing salvage or adjuvant treatment after prostate surgery, with a median follow-up of 3.53 years.

Despite the promising schedule, there was a notable incidence of grade 2 to 3 genitourinary and gastrointestinal toxicities, along with a significant decline in bowel quality of life, indicating the need for further research into safer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated Postprostatectomy Radiation Therapy for Prostate Cancer to Reduce Toxicity and Improve Patient Convenience: A Phase 1/2 Trial. Wages, NA., Sanders, JC., Smith, A., et al.[2022]

In the HYPO-RT-PC trial involving 1180 patients with localized prostate cancer, ultra-hypofractionated radiotherapy showed higher acute toxicity compared to conventional fractionation, particularly in bowel symptoms, but long-term quality of life (QOL) was similar between the two treatment methods up to 6 years post-treatment.

Despite the initial increase in bowel-related issues for patients receiving ultra-hypofractionation, there were no significant differences in urinary, bowel, or sexual functioning between the two groups after the treatment period, indicating that ultra-hypofractionation is a viable option for patients with intermediate-to-high-risk prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial. Fransson, P., Nilsson, P., Gunnlaugsson, A., et al.[2021]

The Scandinavian HYPO-RT-PC trial, involving 1200 men with intermediate-to-high-risk prostate cancer, demonstrated that ultra-hypofractionated radiotherapy (42.7 Gy in seven fractions) is non-inferior to conventional fractionation (78.0 Gy in 39 fractions) in terms of failure-free survival over a median follow-up of 5 years.

While ultra-hypofractionation resulted in more acute urinary and bowel symptoms during treatment, late toxicity rates were similar to those of conventional fractionation, suggesting that ultra-hypofractionation is a safe and effective option for prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Widmark, A., Gunnlaugsson, A., Beckman, L., et al.[2019]

In a study of 63 patients with locally advanced rectal cancer, short course neoadjuvant radiation (25 Gy in five fractions) resulted in a high R0 resection rate of 97% and a low local recurrence rate of only 5%.

The treatment demonstrated acceptable toxicity, with 18% of patients experiencing postoperative complications, while achieving 5-year overall and relapse-free survival rates of 71% and 69%, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-course preoperative radiation therapy for operable rectal cancer. Tankel, K., Hay, J., Ma, R., et al.[2019]

In a study involving 874 men with localized prostate cancer, stereotactic body radiotherapy (SBRT) was found to have similar rates of acute gastrointestinal and genitourinary toxicity compared to conventionally fractionated or moderately hypofractionated radiotherapy, suggesting that shorter treatment courses do not increase immediate side effects.

The study showed that only 12% of patients receiving conventional treatment experienced severe gastrointestinal toxicity, compared to 10% in the SBRT group, and 27% versus 23% for genitourinary toxicity, indicating that SBRT is a safe alternative without compromising patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial. Brand, DH., Tree, AC., Ostler, P., et al.[2022]

In a study involving 396 patients treated with ultra-hypofractionated breast radiotherapy, the five-year local-relapse free survival (LRFS) rate was an impressive 98.8%, indicating high efficacy in controlling breast cancer.

While ultra-hypofractionated radiotherapy showed excellent tumor control, certain regimens, particularly the 5.7 Gy weekly fraction and tumor bed boost, were linked to a higher risk of acute and late skin toxicities, highlighting the need for careful treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large scale experience of two ultrahypofractionated 5 fractions regimes after breast conserving surgery from a single centre. Sauvage, LM., Loap, P., Vu-Bezin, J., et al.[2023]

Recent evidence suggests that hypofractionated radiotherapy for prostate cancer is both safe and effective, particularly with a recommended regimen of 60 Gy in 20 fractions, which showed no significant increase in late toxicity.

While moderate hypofractionation has demonstrated positive 5-year outcomes in large trials, further research is needed for extreme hypofractionation techniques, and their use should currently be restricted to clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionation for prostate cancer: an update. Tiberi, D., Vavassis, P., Nguyen, D., et al.[2019]

In a study of 194 patients with localized prostate cancer treated with ultra-hypofractionated radiotherapy, the 3-year biochemical progression-free survival (b-PFS) rate was 87%, with higher rates for low-risk patients (94%) compared to high-risk patients (66%).

The treatment was found to be safe, with acceptable levels of acute and long-term gastrointestinal and genitourinary toxicity, demonstrating that ultra-hypofractionated radiotherapy can effectively control tumors while minimizing impact on patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Give me five" ultra-hypofractionated radiotherapy for localized prostate cancer: non-invasive ablative approach. Marvaso, G., Riva, G., Ciardo, D., et al.[2018]

In a study involving 457 men with localized prostate cancer, hypofractionated high-dose radiotherapy (60 Gy and 57 Gy) was found to be as well tolerated as conventional radiotherapy (74 Gy) over a median follow-up of 50.5 months, with low rates of grade 2 or worse bowel and bladder toxicities.

The rates of bowel toxicity were 4.3% for the conventional group, 3.6% for the 60 Gy group, and 1.4% for the 57 Gy group, indicating that hypofractionated treatment may not increase the risk of side effects compared to standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial. Dearnaley, D., Syndikus, I., Sumo, G., et al.[2023]

In a pilot study involving 24 patients with low- to intermediate-risk prostate cancer, highly hypofractionated intensity modulated radiation therapy (IMRT) delivered 54 Gy in 15 fractions over 3 weeks resulted in high survival rates: 91.7% biochemical relapse-free survival and 95.8% overall survival at 5 years.

The treatment was well-tolerated, with no severe late gastrointestinal or grade ≥3 genitourinary toxicities observed, suggesting that this approach may be a safe and effective alternative to traditional radiation therapy methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of a Prospective Study on Highly Hypofractionated Intensity Modulated Radiation Therapy for Localized Prostate Cancer for 3 Weeks. Nakamura, K., Ikeda, I., Inokuchi, H., et al.[2023]

A phase II clinical trial involving 31 patients with newly diagnosed, inoperable glioblastoma showed that ultrafractionated radiation therapy, delivering three daily doses of 0.75 Gy, was safe and well tolerated, with no severe acute CNS toxicity observed.

The ultrafractionation regimen resulted in a median progression-free survival of 5.1 months and overall survival of 9.5 months, demonstrating improved outcomes compared to traditional radiation therapy alone, although it did not surpass the results of combined radiation therapy and temozolomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged survival for patients with newly diagnosed, inoperable glioblastoma with 3-times daily ultrafractionated radiation therapy. Beauchesne, P., Bernier, V., Carnin, C., et al.[2022]

References

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

Neoadjuvant Short-Course Radiation Therapy for Rectal Cancer: Trends and Controversies. [2019]

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

Hypofractionated Postprostatectomy Radiation Therapy for Prostate Cancer to Reduce Toxicity and Improve Patient Convenience: A Phase 1/2 Trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. [2019]

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

Short-course preoperative radiation therapy for operable rectal cancer. [2019]

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

Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Large scale experience of two ultrahypofractionated 5 fractions regimes after breast conserving surgery from a single centre. [2023]

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

Hypofractionation for prostate cancer: an update. [2019]

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

"Give me five" ultra-hypofractionated radiotherapy for localized prostate cancer: non-invasive ablative approach. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial. [2023]

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

Long-Term Outcomes of a Prospective Study on Highly Hypofractionated Intensity Modulated Radiation Therapy for Localized Prostate Cancer for 3 Weeks. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Prolonged survival for patients with newly diagnosed, inoperable glioblastoma with 3-times daily ultrafractionated radiation therapy. [2022]