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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating locally advanced rectal cancer. It focuses on using ultra-fractionated radiotherapy, a precise type of radiation treatment, combined with chemotherapy to improve patient response. The trial tests different radiation dose levels to determine the most effective one. Individuals diagnosed with rectal adenocarcinoma who have not received prior treatment may be suitable candidates for this study. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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 prior data suggests that this radiotherapy technique is safe for rectal cancer?

Research shows that ultra-fractionated radiotherapy, a type of focused radiation treatment, is generally safe. Previous studies on similar treatments, such as hypofractionated radiotherapy, found that patients tolerated it well and experienced manageable side effects.

This trial tests different dose levels. It is important to note that this is an early-stage trial. While the treatment appears promising in terms of safety, researchers are closely monitoring it to ensure safety for all participants. As always, those considering joining a trial should discuss potential risks with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ultrafractionated radiotherapy for rectal cancer because it offers a novel approach to radiation delivery. Unlike traditional radiotherapy, which is typically given in larger doses over a few weeks, ultrafractionated radiotherapy delivers smaller doses over a shorter period. This method aims to minimize damage to surrounding healthy tissues while effectively targeting the tumor. The potential for fewer side effects and a more convenient treatment schedule makes this approach particularly appealing for patients and healthcare providers alike.

What evidence suggests that ultra-fractionated radiotherapy might be an effective treatment for rectal cancer?

Studies have shown that ultra-fractionated radiotherapy, which involves delivering higher doses of radiation in a shorter time, can be promising for treating rectal cancer. For patients with locally advanced rectal cancer, a short course of radiation followed by surgery yields results similar to traditional longer treatments. This method may balance effectiveness with side effects. Generally, administering larger doses of radiation in fewer sessions, known as hypofractionation, often results in similar survival rates for both prostate and rectal cancers. This trial will explore different dose levels of ultra-fractionated radiotherapy to assess its effectiveness in controlling cancer with potentially fewer treatment sessions. ^{1 2 4 6 7}

Who Is on the Research Team?

Nina Sanford, MD

Principal Investigator

UT SOUTHWESTERN medical CENTRE

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04677413

Ultra-fractionated Radiotherapy for Rectal Cancer The rationale of this clinical trial is to assess the feasibility of selective non-operative management for locally advanced rectal cancer.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11701464/

Evidence-based clinical recommendations for ... For recurrent rectal cancer, the use of stereotactic body radiotherapy offers a promising approach for re-irradiation, balancing efficacy and ...

3. withpower.com withpower.com/trial/phase-1-rectal-neoplasms-5-2021-b017e

Ultra-fractionated Radiotherapy for Rectal Cancer Short-course radiation followed by early surgery provides similar oncologic outcomes as long-course chemoradiation for patients with locally advanced rectal ...

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK595075/

EXECUTIVE SUMMARY - Hypofractionation Radiation ... For individuals with prostate and rectal cancer, hypofractionation therapy probably results in little to no difference in overall survival and may result in ...

5. clinicaloncologyonline.net clinicaloncologyonline.net/article/S0936-6555(22)00138-8/pdf

When Less is More: The Rising Tide of Hypofractionation In randomised studies, a single fraction (24 Gy) and two fractions (24 Gy in two fractions) showed superior pain control outcome at 3 months with low rates of ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04677413/ultra-fractionated-radiotherapy-for-rectal-cancer

Ultra-fractionated Radiotherapy for Rectal Cancer This clinical trial is to assess the feasibility of selective non-operative management for locally advanced rectal cancer using dose-escalated ultra- ...

7. e-roj.org e-roj.org/journal/view.php?number=1621

Feasibility and safety study of ultra-hypofractionated ... This feasibility study showed that hypofractionated neoadjuvant radiotherapy to margins-at-risk is safe. We have demonstrated early results to ...