Radiotherapy for Rectal Cancer

Recruiting at 1 trial location

Overseen By Marianna Perna, CCRP,CCRC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Must not be taking: Warfarin, Phenytoin, Sorivudine

Disqualifiers: Previous pelvic radiotherapy, Metastatic disease, Cardiorespiratory comorbidity, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

48 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications, but you cannot participate if you are taking warfarin, phenytoin, or sorivudine.

What data supports the effectiveness of the treatment Radiotherapy for Rectal Cancer?

External beam radiotherapy (EBRT) has been shown to be effective in treating various cancers, such as prostate cancer, by reducing cancer recurrence and improving survival rates. This suggests that EBRT could also be beneficial for rectal cancer treatment. ^{1 2 3 4 5}

Is external beam radiotherapy (EBRT) generally safe for humans?

External beam radiotherapy (EBRT) can cause long-term side effects like bowel injury and rectal bleeding, especially when used for prostate and rectal cancers. These side effects are important to consider when evaluating the safety of EBRT. ^{6 7 8 9 10}

How is radical external beam radiotherapy (EBRT) unique for treating rectal cancer?

Radical external beam radiotherapy (EBRT) is unique because it uses high-energy rays from outside the body to target and kill cancer cells, which is different from treatments like surgery or chemotherapy that involve removing the tumor or using drugs. This method is non-invasive and can be precisely directed at the cancerous area, minimizing damage to surrounding healthy tissue. ^{3 4 11 12 13}

What is the purpose of this trial?

This trial involves treating patients with rectal cancer using a combination of radiation and chemotherapy. The radiation aims to kill cancer cells, and the chemotherapy makes these cells more sensitive to the radiation. This approach targets patients whose cancer may not respond well to surgery alone.

Research Team

Neil Kopek, M.D.

Principal Investigator

Radiation Oncologist

Eligibility Criteria

This trial is for adults over 18 with rectal cancer that hasn't spread to other parts of the body. They should be fit enough for surgery, have certain MRI findings like muscle or lymph node involvement, and good organ function. People can't join if they've had pelvic radiation before, have severe bowel issues without a stoma, serious heart/lung problems, another recent cancer (except skin or cervical), specific genetic conditions affecting drug metabolism, are on certain medications, or are pregnant without contraception.

Inclusion Criteria

My cancer has spread to the fatty tissue near my rectum.

Ability to comply with oral medication

I am medically cleared for cancer surgery.

Exclusion Criteria

I am not fit for the study treatment or surgery.

I have been diagnosed with Gilbert's syndrome.

My cancer is early stage and hasn't spread to my veins.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Chemotherapy

Participants receive pelvic radiotherapy to a dose of 45Gy in 25 fractions with a tumor boost to a dose of 9Gy in 5 fractions, combined with radiosensitizing chemotherapy

6 weeks

Monitoring

Participants are closely monitored through endoscopy and imaging for response to treatment and relapse

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Radical external beam radiotherapy

Trial Overview The study tests high-dose radiotherapy combined with chemotherapy in rectal cancer patients. The goal is to see if this treatment can allow some patients to avoid surgery by closely monitoring them afterwards and only operating if the cancer doesn't respond completely or comes back locally.

Participant Groups

Group I: Radical External Beam RT for Colorectal Ca Experimental Treatment 1 Intervention

A single arm consisting of: Radical external beam RT dose of 54 Gy in 30fx with radiosensitizing chemotherapy as per institutional standard

Radical external beam radiotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as External Beam Radiation Therapy for:

• Rectal cancer
• Colorectal cancer
• Prostate cancer
• Cervical cancer
• Vulval cancer
• Vaginal cancer
• Bladder cancer
• Anal cancer

Approved in United States as External Beam Radiation Therapy for:

• Rectal cancer
• Colorectal cancer
• Prostate cancer
• Cervical cancer
• Vulval cancer
• Vaginal cancer
• Bladder cancer
• Anal cancer
• Breast cancer
• Lung cancer

Approved in Canada as External Beam Radiation Therapy for:

• Rectal cancer
• Colorectal cancer
• Prostate cancer
• Cervical cancer
• Vulval cancer
• Vaginal cancer
• Bladder cancer
• Anal cancer

Approved in Japan as External Beam Radiation Therapy for:

• Rectal cancer
• Colorectal cancer
• Prostate cancer
• Cervical cancer
• Vulval cancer
• Vaginal cancer
• Bladder cancer
• Anal cancer

Approved in China as External Beam Radiation Therapy for:

• Rectal cancer
• Colorectal cancer
• Prostate cancer
• Cervical cancer
• Vulval cancer
• Vaginal cancer
• Bladder cancer
• Anal cancer

Approved in Switzerland as External Beam Radiation Therapy for:

• Rectal cancer
• Colorectal cancer
• Prostate cancer
• Cervical cancer
• Vulval cancer
• Vaginal cancer
• Bladder cancer
• Anal cancer

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Findings from Research

In a study of 54,642 prostate cancer patients, low-dose-rate brachytherapy boost (LDR-BB) was associated with significantly higher gastrointestinal (GI) toxicity (32.3%) compared to high-dose-rate brachytherapy boost (HDR-BB) (16.7%) and external beam radiation therapy (EBRT) monotherapy (18.7%).

High-dose-rate brachytherapy boost (HDR-BB) resulted in lower incidences of skeletal-related events (2.4%) and prostate cancer-specific mortality (2.7%) compared to EBRT monotherapy (2.8% and 3.5%, respectively), indicating HDR-BB may offer better long-term outcomes in these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of High-Dose-Rate and Low-Dose-Rate Brachytherapy Boost on Toxicity, Functional and Cancer Outcomes in Patients Receiving External Beam Radiation Therapy for Prostate Cancer: A National Population-Based Study. Parry, MG., Nossiter, J., Sujenthiran, A., et al.[2021]

In a study of 113 cervical cancer patients treated with a median dose of 50.4 Gy of small pelvic external beam radiotherapy (EBRT), the 5-year overall survival rate was 82%, indicating effective long-term outcomes.

The treatment showed acceptable toxicity levels, with no severe acute side effects and only 8 patients experiencing late grade ≥ 3 toxicity, suggesting that small pelvic EBRT can be a safe alternative to whole pelvic EBRT for selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Small Pelvic Radiotherapy in Patients with Cervical Cancer Having Intermediate Risk Factors Only - Is It Sufficient? Yuce Sari, S., Guler, OC., Gultekin, M., et al.[2018]

Between 1996 and 2005, there was a notable trend in Japan towards treating more patients with early-stage prostate cancer (T1 to T2) and administering higher radiation doses, increasing from a median of 65.0 Gy to 70 Gy.

The use of advanced conformal therapy significantly rose from 49.1% to 84.9% during the same period, indicating improvements in treatment technology and techniques, while the percentage of patients receiving hormone therapy remained stable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radical external beam radiotherapy for clinically localized prostate cancer in Japan: changing trends in the patterns of care process survey. Ogawa, K., Nakamura, K., Sasaki, T., et al.[2019]

External beam radiotherapy (EBRT) is an effective treatment for relieving symptoms caused by bone metastases in prostate cancer patients.

This review specifically compares the effectiveness of single fraction radiotherapy to multiple fraction radiotherapy, highlighting the need for further analysis on which approach may provide better outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single fraction radiotherapy versus multiple fraction radiotherapy for bone metastases in prostate cancer patients: comparative effectiveness. Yoon, F., Morton, GC.[2020]

External-beam radiotherapy (EBRT) has been effectively used for over 30 years to treat prostate adenocarcinoma, demonstrating significant improvements in cause-specific survival and freedom from PSA progression.

Recent advancements in radiation techniques have enhanced the safety and efficacy of EBRT, making it a viable treatment option for early-stage, locally advanced, and metastatic prostate cancer, while managing side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External-beam radiotherapy in the management of carcinoma of the prostate. Zlotecki, RA.[2017]

In a study of 42 patients treated with external beam radiotherapy for prostate cancer, those with higher anorectal dysfunction scores exhibited significant structural changes in the rectal mucosa and altered biomechanical properties compared to those with lower scores.

The findings suggest that long-term anorectal dysfunction after radiotherapy is caused by a combination of rectal mucosal injury, increased sensitivity, and reduced functional capacity of the anal sphincter.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathophysiology of late anorectal dysfunction following external beam radiotherapy for prostate cancer. Petersen, SE., Bregendahl, S., Langschwager, M., et al.[2015]

In a study of 304 rectal carcinoma patients treated with external beam radiotherapy (EBRT) and/or chemotherapy, 19% developed treatment-induced bowel injury within 5 years, highlighting a significant risk associated with this treatment.

Factors increasing the risk of bowel injury included transanal excision, higher radiation doses, and older age, indicating that careful treatment planning and dose management are crucial to minimize complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The incidence and clinical consequences of treatment-related bowel injury. Miller, AR., Martenson, JA., Nelson, H., et al.[2019]

In a study of 231 patients treated with external beam radiation therapy (EBRT) for prostate cancer, the 5-year overall survival rate was 80.3%, with 90% of patients reporting excellent anorectal function and only 14.3% experiencing rectal bleeding, indicating low toxicity.

Preliminary results from a feasibility study of conformal radiotherapy, which escalated doses from 68 to 80 Gy, suggest good early tolerance, potentially improving local control and survival outcomes in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curative external beam radiotherapy for prostate carcinoma: results in 231 patients treated in Lyon. Gerard, JP., Xie, C., Carrie, C., et al.[2019]

In a study of 333 prostate cancer patients treated with external beam radiation therapy (EBRT), severe acute urinary toxicity occurred in 5.4% and severe rectal toxicity in 1.5%, indicating that the treatment is generally well-tolerated.

Patients with pre-existing lower urinary tract symptoms experienced higher rates of acute urinary toxicity, while rectal toxicity was linked to higher radiation doses and the use of anticoagulant therapy, highlighting the importance of patient history in predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of urinary and rectal toxicity after external conformed radiation therapy in prostate cancer: Correlation between clinical, tumour and dosimetric parameters and radical and postoperative radiation therapy. Martínez-Arribas, CM., González-San Segundo, C., Cuesta-Álvaro, P., et al.[2019]

In a study of 32 patients receiving External Beam Radiotherapy (EBRT) for bone metastases, 41% experienced a pain flare, which is defined as a significant increase in pain or analgesia intake, with a median duration of 3 days.

The incidence and duration of pain flare observed in this study align with findings from international studies, indicating that pain flare is a common side effect of EBRT for bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An investigation into the incidence of pain flare in patients undergoing radiotherapy for symptomatic bone metastases. Goldfinch, R., White, N.[2018]

Fractionated beam radiotherapy (EBRT) and brachytherapy, while different in technique, can achieve similar biological effective doses (BED) under certain conditions, particularly with short irradiation times.

This study uses mathematical models to demonstrate the correlation between these two radiotherapy methods, suggesting that they may have comparable effects on tumor control and tissue response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated beam radiotherapy is a special case of continuous beam radiotherapy when irradiation time is small. Biswas, J., Rajguru, TK., Choudhury, KB., et al.[2018]

Definitive external beam radiotherapy (EBRT) for unresectable soft-tissue sarcomas shows promising 5-year local control rates of 28-73% for photon therapies and 52-69% for particle therapies, based on a systematic review of 29 studies involving 1409 patients.

While doses of 64-66 Gy appear to be safe and effective, higher doses (≥68 Gy) significantly increase the risk of severe adverse events, highlighting the need for careful dose management in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a place for definitive radiotherapy in the treatment of unresectable soft-tissue sarcoma? A systematic review. Allignet, B., Sunyach, MP., Geets, X., et al.[2022]

In a study of 189 prostate cancer patients treated with low-dose-rate brachytherapy, those who also received supplemental external beam radiotherapy (EBRT) had a significantly higher 5-year biochemical failure-free survival rate of 80% compared to 59% for those who did not receive EBRT (P < 0.01).

The use of EBRT was the only significant factor associated with improved biochemical control in the multivariate analysis, highlighting its potential role in enhancing treatment outcomes for patients with adverse disease features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of external beam radiotherapy with low-dose-rate brachytherapy in treatment of prostate cancer. Jani, AB., Feinstein, JM., Pasciak, R., et al.[2015]

References

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

Impact of High-Dose-Rate and Low-Dose-Rate Brachytherapy Boost on Toxicity, Functional and Cancer Outcomes in Patients Receiving External Beam Radiation Therapy for Prostate Cancer: A National Population-Based Study. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Adjuvant Small Pelvic Radiotherapy in Patients with Cervical Cancer Having Intermediate Risk Factors Only - Is It Sufficient? [2018]

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

Radical external beam radiotherapy for clinically localized prostate cancer in Japan: changing trends in the patterns of care process survey. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Single fraction radiotherapy versus multiple fraction radiotherapy for bone metastases in prostate cancer patients: comparative effectiveness. [2020]

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

External-beam radiotherapy in the management of carcinoma of the prostate. [2017]

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

Pathophysiology of late anorectal dysfunction following external beam radiotherapy for prostate cancer. [2015]

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

The incidence and clinical consequences of treatment-related bowel injury. [2019]

8. Australia pubmed.ncbi.nlm.nih.gov

Curative external beam radiotherapy for prostate carcinoma: results in 231 patients treated in Lyon. [2019]

9. Spain pubmed.ncbi.nlm.nih.gov

Predictors of urinary and rectal toxicity after external conformed radiation therapy in prostate cancer: Correlation between clinical, tumour and dosimetric parameters and radical and postoperative radiation therapy. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

An investigation into the incidence of pain flare in patients undergoing radiotherapy for symptomatic bone metastases. [2018]

11. India pubmed.ncbi.nlm.nih.gov

Fractionated beam radiotherapy is a special case of continuous beam radiotherapy when irradiation time is small. [2018]

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

Is there a place for definitive radiotherapy in the treatment of unresectable soft-tissue sarcoma? A systematic review. [2022]

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

Role of external beam radiotherapy with low-dose-rate brachytherapy in treatment of prostate cancer. [2015]