Intense Radiotherapy for Prostate Cancer

Recruiting at 11 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Sir Mortimer B. Davis - Jewish General Hospital

Must be taking: LHRH agonists

Disqualifiers: Other malignancies, Small-cell carcinoma, 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: 5 weeks for hypofractionated, 7-8 weeks for conventional

329 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must not have received any cytotoxic anticancer therapy for prostate cancer before joining the trial.

What data supports the effectiveness of the treatment Intense Radiotherapy for Prostate Cancer?

Research shows that hypofractionated radiotherapy, which uses larger daily doses of radiation, can improve prostate cancer control compared to conventional methods. This approach may offer better outcomes by delivering higher doses to the prostate while minimizing harm to surrounding tissues. ^{1 2 3 4 5}

Is intense radiotherapy for prostate cancer safe for humans?

Intense radiotherapy, including hypofractionated radiotherapy, is generally considered safe for prostate cancer patients, though it may cause some side effects like urinary and rectal issues. Studies show it is well-tolerated, with no significant increase in severe side effects compared to conventional methods. ^{6 7 8 9 10}

How does intense radiotherapy for prostate cancer differ from other treatments?

Intense radiotherapy for prostate cancer, specifically hypofractionated radiation therapy, delivers larger doses of radiation in fewer sessions compared to conventional methods. This approach can improve treatment effectiveness and convenience by reducing the number of visits needed, while advanced techniques like intensity-modulated radiation therapy (IMRT) help protect surrounding healthy tissues. ^{2 3 4 11 12}

What is the purpose of this trial?

In North America, around a quarter a million men are diagnosed with prostate cancer every year, and about 31,000 patients will die of their disease each year. Like other western countries, the incidence in Canada has increased due to an aging population and prostate specific antigen (PSA) screening. This has led to a significant demand on cancer care services for these patients. Prostate cancer patient with high risk features are more often treated with external beam radiation therapy (EBRT) plus two to three years of hormonal manipulation (luteinizing hormone-releasing hormone \[LHRH\] agonist). The most common radiation dose treatment for these patients is 74-78 Gy in 37-39 daily fractions of 180-200 cGy for a treatment length of 7.5 weeks. This fraction size is believed to offer the best balance between desired tumour kill and unwanted normal tissue injury. Larger fraction sizes of more than 250 cGy (hypofractionation) are usually avoided for curative therapy because late reacting normal tissues. However prostate cancer cells have a unique radiobiology characteristic that suggests that hypofractionated radiotherapy is more efficient at prostate tumour killing than standard fractionation is, and will produce equivalent tumour control with a lower total dose and a shorter overall treatment time. Improved target localization techniques and conformal radiation therapy technology have allowed for dose escalation and hypofractionated radiation delivery in these circumstances with minimal or no increased toxicities. This trial is designed to determine whether high risk prostate cancer patients can be safely treated with a dose escalation hypofractionated radiation therapy in 5 weeks as opposed to the usual 7-8 weeks. These patients will be randomized to either the usual 76 Gy in 38 fractions or 68 Gy in 25 fractions. 3D-Conformal Radiotherapy (3D-CRT) or Intensity Modulated Radiotherapy (IMRT) will be used to deliver the required radiation dose. Patients will also receive 28 months of androgen deprivation therapy (LHRH agonist). The primary outcome of the study is the acute and delayed toxicity and the secondary outcomes include biochemical failure, prostate specific mortality rate, bone metastases free survival, the prognostic and predictive value of several biological variables: presence of the PTEN deletion; expression of FoxP3 gene variants, topoisomerase 2α and cancer testis antigens; expression of X chromosome-linked micro-RNAs; presence of TMRSS2-ERG gene fusion and quality of life. It is planned to recruit 250 patients to this study.

Research Team

Dr. Tamim Niazi, MDCM

Principal Investigator

Jewish General Hospital

Eligibility Criteria

This trial is for men with high-risk prostate cancer, defined as T3 or T4 stage, Gleason Score over 8, or PSA levels above 20. They must have no metastases on scans and a good performance status (able to carry out daily activities). Prior hormonal therapy is allowed if started within 28 days before the trial.

Inclusion Criteria

Hemoglobin > 100 g/L

My prostate cancer is high risk with a high Gleason score or PSA level.

I started androgen suppression therapy for my cancer less than 28 days ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either hypofractionated or conventional radiotherapy along with androgen deprivation therapy

5 weeks for hypofractionated, 7-8 weeks for conventional

Hormonal Therapy

Participants receive 28 months of androgen deprivation therapy (LHRH agonist)

28 months

Follow-up

Participants are monitored for acute and delayed toxicity, biochemical failure, and survival outcomes

6-8 years

Treatment Details

Interventions

• Conventional Radiation Therapy
• Hypofractionation Radiation Therapy

Trial Overview The study tests whether a shorter, higher-dose radiation treatment (68 Gy in 25 fractions) can be as safe and effective as the standard longer course (76 Gy in 38 fractions) for prostate cancer. Both groups will also receive hormone therapy and are monitored for side effects and cancer control.

Participant Groups

Group I: Hypofractionation Experimental Treatment 1 Intervention

One phase technique (IMRT or 3D-CRT): radiotherapy to the prostate + pelvic lymphnodes

Group II: Conventional Experimental Treatment 1 Intervention

two-phase technique (IMRT or 3D-CRT): 1) whole pelvis including the prostate and regional lymph nodes; 2) boost to the prostate

Who Is Running the Clinical Trial?

Sir Mortimer B. Davis - Jewish General Hospital

Lead Sponsor

Trials

61

Recruited

25,800+

Findings from Research

In a study of 124 patients with high-risk prostate cancer, hypofractionated radiotherapy using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) showed a low incidence of severe acute toxicity, with only 1.6% of patients experiencing grade 3 or higher side effects.

The treatment resulted in a promising five-year biochemical relapse-free survival rate of 86.5%, indicating its efficacy in preventing cancer recurrence after radical prostatectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated Postoperative IMRT in Prostate Carcinoma: A Phase I/II Study. Macchia, G., Siepe, G., Capocaccia, I., et al.[2021]

Hypofractionated radiotherapy for prostate cancer, which delivers larger doses in fewer sessions, has shown improved biochemical control of the disease, supported by multiple clinical trials.

Advanced radiation techniques like 3D conformal radiotherapy and intensity modulated radiation therapy enable higher doses to the prostate while protecting surrounding healthy tissues, making hypofractionation a safer and more effective option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of hypofractionated radiotherapy for prostate cancer. Spyropoulou, D., Kardamakis, D.[2021]

Moderate hypofractionated radiotherapy for prostate cancer is associated with a 6.3% increase in acute grade ≥ 2 gastrointestinal toxicity compared to standard fractionation, indicating a need for careful monitoring and management of these symptoms.

There was no significant increase in acute genitourinary toxicity or late toxicity levels between moderate hypofractionation and standard fractionation, suggesting that while acute GI symptoms may be more common, overall safety profiles for late effects are similar.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and late toxicity patterns of moderate hypo-fractionated radiotherapy for prostate cancer: A systematic review and meta-analysis. Sinzabakira, F., Brand, V., Heemsbergen, WD., et al.[2023]

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 phase 3 trial involving 804 patients with localized prostate cancer, hypofractionated radiotherapy showed a 5-year relapse-free survival rate of 80.5%, which was not significantly better than the 77.1% rate for conventionally fractionated radiotherapy, indicating no superiority in treatment outcomes.

Both treatment regimens were found to be safe, with no treatment-related deaths reported, suggesting that while hypofractionation is not superior, it does not increase the risk of severe adverse effects compared to conventional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated versus conventionally fractionated radiotherapy for patients with localised prostate cancer (HYPRO): final efficacy results from a randomised, multicentre, open-label, phase 3 trial. Incrocci, L., Wortel, RC., Alemayehu, WG., et al.[2022]

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 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 a study involving 200 patients with early-stage prostate cancer, extreme hypofractionated proton therapy (36.25 GyE in five fractions) demonstrated feasibility with a low rate of acute toxicity, where no patients experienced severe (G3) side effects.

After a median follow-up of 36 months, the treatment showed promising effectiveness, with no local recurrences of cancer and a low PSA relapse rate of 1.08% in low-risk and 6.5% in intermediate-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extreme hypofractionated proton radiotherapy for prostate cancer using pencil beam scanning: Dosimetry, acute toxicity and preliminary results. Kubeš, J., Vondráček, V., Andrlik, M., et al.[2020]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Hypofractionated Postoperative IMRT in Prostate Carcinoma: A Phase I/II Study. [2021]

2. Poland pubmed.ncbi.nlm.nih.gov

The rationale behind hypofractionated high-dose intensity-modulated radiotherapy in patients with localized prostate cancer: short review. [2013]

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

Randomized Trial of Hypofractionated, Dose-Escalated, Intensity-Modulated Radiation Therapy (IMRT) Versus Conventionally Fractionated IMRT for Localized Prostate Cancer. [2022]

4. Egypt pubmed.ncbi.nlm.nih.gov

Review of hypofractionated radiotherapy for prostate cancer. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Comparison of Treatment-Related Toxicity With Hypofractionated or Conventionally Fractionated Radiation Therapy for Prostate Cancer: A National Population-Based Study. [2021]

6. Ireland pubmed.ncbi.nlm.nih.gov

Acute and late toxicity patterns of moderate hypo-fractionated radiotherapy for prostate cancer: A systematic review and meta-analysis. [2023]

7. 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]

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

Hypofractionated versus conventionally fractionated radiotherapy for patients with localised prostate cancer (HYPRO): final efficacy results from a randomised, multicentre, open-label, phase 3 trial. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Hypofractionation for prostate cancer: an update. [2019]

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

Extreme hypofractionation for early prostate cancer: Biology meets technology. [2018]

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. Australia pubmed.ncbi.nlm.nih.gov

Extreme hypofractionated proton radiotherapy for prostate cancer using pencil beam scanning: Dosimetry, acute toxicity and preliminary results. [2020]