Hypofractionated Radiation Therapy for Prostate Cancer

Overseen By Acara Carter

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: University of Maryland, Baltimore

Must not be taking: Anticoagulants, Clopidogrel

Disqualifiers: Metastases, Lymph node involvement, 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: 1

Duration: 12-20 fractions

18 Participants Needed

Trial Summary

What is the purpose of this trial?

A phase I trial to determine the safety of delivering three sequentially shorter RT schedules (20, 16, and 12 fractions) of HypoFx pelvic nodal RT in combination with a HypoFx, simultaneous integrated boost (SIB) to the prostate that have been designed to incrementally increased the biological equivalent dose (BED) to prostate cancer, while maintaining a constant BED to normal tissue toxicity.

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

The trial does not specify if you need to stop taking your current medications, but it does exclude patients who are on full-dose anticoagulation or clopidogrel. If you are taking 81 mg of Aspirin daily, you can still participate.

What data supports the effectiveness of the treatment Hypofractionated Radiation Therapy for Prostate Cancer?

Research shows that hypofractionated radiation therapy (HFRT) for prostate cancer is effective and safe, with studies indicating improved control of cancer with higher radiation doses. Advanced techniques like intensity-modulated radiation therapy (IMRT) help deliver these doses while protecting healthy tissues, making the treatment more convenient and potentially more effective. ^{1 2 3 4 5}

Is hypofractionated radiation therapy safe for humans?

Hypofractionated radiation therapy (HFRT) for prostate cancer is generally considered safe, but it may increase the risk of gastrointestinal (GI) and genitourinary (GU) side effects compared to traditional radiation therapy. Several studies have found HFRT to be well tolerated, although some patients may experience greater acute GI toxic effects. ^{1 6 7 8 9}

How is hypofractionated radiation therapy different from other treatments for prostate cancer?

Hypofractionated radiation therapy (HFRT) for prostate cancer is unique because it delivers higher doses of radiation in fewer sessions, making it more convenient and potentially more cost-effective for patients. This approach may improve therapeutic outcomes by using larger daily doses, and advanced techniques like intensity modulated radiation therapy (IMRT) help target the prostate while sparing surrounding healthy tissue. ^{1 3 5 8 10}

Eligibility Criteria

Men over 18 with intermediate to high-risk prostate cancer, without bone metastases or previous chemotherapy for prostate cancer. They must have a good performance status and be able to consent. Excluded are those with prior pelvic radiation, certain blood thinners, autoimmune diseases that could worsen with radiation, or any severe condition that might complicate participation.

Inclusion Criteria

I am fully active or can carry out light work.

Patient must be able to provide study specific informed consent prior to study entry.

My recent scans show no cancer spread to bones.

Exclusion Criteria

I am scheduled for a targeted radiation treatment for my prostate.

I have had surgery or specific treatments for prostate cancer.

I do not have an autoimmune disease that my doctor thinks would make pelvic radiation unsafe for me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hypofractionated accelerated pelvic nodal radiotherapy with a simultaneously integrated prostate boost

12-20 fractions

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

1 month after treatment, every 3 months for year 1, and every 6 months during year 2

Treatment Details

Interventions

• Hypofractionated Radiation Therapy

Trial Overview This phase I trial tests the safety of three different schedules of Hypofractionated Radiation Therapy targeting the pelvic lymph nodes and prostate. The therapy aims to increase the dose to the cancer while keeping it safe for normal tissues.

Participant Groups

Group I: Dose Level 3 Experimental Treatment 1 Intervention

Dose schedules were calculated to maintain similar BED for late normal tissue injury (α/β= 3.0 Gy), with an increased BED for PC (α/β= 1.5Gy). Patients be treated with 12 fractions. A total of 6 patients will be treated at the dose that is determined to be Maximum Tolerated Dose.

Group II: Dose Level 2 Experimental Treatment 1 Intervention

Dose schedules were calculated to maintain similar BED for late normal tissue injury (α/β= 3.0 Gy), with an increased BED for PC (α/β= 1.5Gy). Patients be treated with 16 fractions. A total of 6 patients will be treated at the dose that is determined to be Maximum Tolerated Dose.

Group III: Dose Level 1 Experimental Treatment 1 Intervention

Dose schedules were calculated to maintain similar BED for late normal tissue injury (α/β= 3.0 Gy), with an increased BED for PC (α/β= 1.5Gy). Patients be treated with 20 fractions. A total of 6 patients will be treated at the dose that is determined to be Maximum Tolerated Dose.

Hypofractionated Radiation Therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Approved in European Union as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Approved in Canada as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Findings from Research

In a study involving 160 prostate cancer patients, both hypofractionated radiation therapy regimens (56 Gy in 16 fractions and 67 Gy in 25 fractions) were found to be safe, with manageable levels of acute gastrointestinal and urinary toxicity.

Acute grade ≥2 gastrointestinal toxicity occurred in 26% of patients in the 56 Gy group and 20% in the 67 Gy group, indicating that both treatment schedules are effective options with acceptable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

4 Weeks Versus 5 Weeks of Hypofractionated High-dose Radiation Therapy as Primary Therapy for Prostate Cancer: Interim Safety Analysis of a Randomized Phase 3 Trial. Fonteyne, V., Sarrazyn, C., Swimberghe, M., et al.[2022]

In a phase II study involving 40 high-risk prostate cancer patients, dose-escalated hypofractionated radiotherapy (hfrt) combined with androgen suppression therapy was found to be feasible, delivering 75 Gy in 25 fractions with minimal acute gastrointestinal and genitourinary toxicities.

Only 16.6% of patients experienced grade 2 genitourinary toxicity and 12.9% experienced gastrointestinal toxicity, indicating that the treatment can be administered safely while still targeting the pelvic lymph nodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity of hypofractionated intensity-modulated radiotherapy for prostate cancer. Drodge, CS., Boychak, O., Patel, S., et al.[2018]

In a study of 855 prostate cancer patients treated post-surgery, hypofractionated radiotherapy (HF) showed similar biochemical control rates and overall survival compared to conventionally fractionated radiotherapy (CF), indicating that both treatment methods are equally effective.

Patients receiving HF experienced significantly fewer acute gastrointestinal and genitourinary side effects, suggesting that HF may be a safer option in terms of immediate toxicity after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of moderate hypofractionation with volumetric modulated arc therapy versus conventional 3D-radiotherapy after radical prostatectomy. Moll, M., D'Andrea, D., Zaharie, A., et al.[2022]

In a study of 41 patients with high-risk localized prostate cancer, combining whole-pelvis irradiation with a stereotactic body radiotherapy (SBRT) boost resulted in a high 4-year biochemical failure-free survival rate of 91.9%, indicating effective cancer control.

The treatment was associated with minimal toxicity, with no severe (grade 3) gastrointestinal or genitourinary side effects reported, suggesting that this approach is safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The early result of whole pelvic radiotherapy and stereotactic body radiotherapy boost for high-risk localized prostate cancer. Lin, YW., Lin, LC., Lin, KL.[2020]

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]

In a clinical trial involving 201 patients with prostate cancer, the use of a hyaluronic acid rectal spacer significantly improved rectal dosimetry, with 98.5% of patients achieving a 25% or greater reduction in rectal volume receiving radiation, far exceeding the 70% target.

The spacer also reduced the incidence of acute grade 2 or higher gastrointestinal toxic effects, with only 2.9% of patients in the spacer group experiencing these effects compared to 13.8% in the control group, indicating a safer treatment option for hypofractionated radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy: A Randomized Clinical Trial. Mariados, NF., Orio, PF., Schiffman, Z., et al.[2023]

In a study of 132 prostate cancer patients receiving hypofractionated radiation therapy (HFRT), the treatment was found to be feasible with low acute gastrointestinal and genitourinary toxicities, with only 4% experiencing grade 3 toxicity.

The average prostate symptom score increased during treatment but returned to near baseline levels three months after completion, indicating manageable side effects and a positive impact on quality of life post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Therapy for Prostate Cancer Using HYpofractionation Directed by UltraSound (RAPHYDUS): A Brazilian Public Health Care System Study. Faustino, FLC., Altei, WF., Canton, HP., et al.[2022]

In a phase II study involving 111 high-risk prostate cancer patients, hypofractionated radiation therapy (HFRT) was found to be well tolerated, with no significant difference in acute gastrointestinal (GI) or genitourinary (GU) toxicity compared to conventionally fractionated radiation therapy (CFRT).

Both HFRT and CFRT resulted in similar 3-year biochemical recurrence-free survival rates (97.3% for HFRT vs 91.0% for CFRT) and overall survival rates (94.8% for HFRT vs 100.0% for CFRT), indicating that HFRT is a safe and effective treatment option for high-risk prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of the CHIRP Trial: A Phase II Prospective Randomized Trial of Conventionally Fractionated Versus Moderately Hypofractionated Prostate and Pelvic Nodal Radiation Therapy in Patients With High-Risk Prostate Cancer. Wang, MH., Vos, LJ., Yee, D., et al.[2021]

In a study of 59 low-risk prostate cancer patients treated with image-guided hypofractionated radiotherapy (HFRT), the treatment showed excellent outcomes with a 4-year overall survival rate of 100% and a biochemical free survival rate of 97.4%.

While HFRT resulted in lower rates of acute grade 2-3 genitourinary (GU) toxicity compared to conventional fractionation (CFRT), it was associated with a higher cumulative incidence of low-grade late GU toxicity, indicating a trade-off in side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided hypofractionated radiotherapy in low-risk prostate cancer patients. Valeriani, M., Carnevale, A., Agolli, L., et al.[2021]

In a study of 820 patients with localized prostate cancer, hypofractionated radiation therapy showed similar 5-year relapse-free survival rates compared to conventional radiation therapy, but it did not demonstrate noninferiority in terms of genitourinary and gastrointestinal quality of life.

While hypofractionation did not perform as well for urinary and gastrointestinal symptoms, it was found to be noninferior for other aspects of quality of life, such as symptoms related to androgen deprivation therapy and sexual function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderate Hypofractionation in Intermediate- and High-Risk, Localized Prostate Cancer: Health-Related Quality of Life From the Randomized, Phase 3 HYPRO Trial. Wortel, RC., Oomen-de Hoop, E., Heemsbergen, WD., et al.[2019]

References

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

4 Weeks Versus 5 Weeks of Hypofractionated High-dose Radiation Therapy as Primary Therapy for Prostate Cancer: Interim Safety Analysis of a Randomized Phase 3 Trial. [2022]

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

Acute toxicity of hypofractionated intensity-modulated radiotherapy for prostate cancer. [2018]

3. Germany pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of moderate hypofractionation with volumetric modulated arc therapy versus conventional 3D-radiotherapy after radical prostatectomy. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The early result of whole pelvic radiotherapy and stereotactic body radiotherapy boost for high-risk localized prostate cancer. [2020]

5. Egypt pubmed.ncbi.nlm.nih.gov

Review of hypofractionated radiotherapy for prostate cancer. [2021]

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

Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy: A Randomized Clinical Trial. [2023]

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

Radiation Therapy for Prostate Cancer Using HYpofractionation Directed by UltraSound (RAPHYDUS): A Brazilian Public Health Care System Study. [2022]

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

Clinical Outcomes of the CHIRP Trial: A Phase II Prospective Randomized Trial of Conventionally Fractionated Versus Moderately Hypofractionated Prostate and Pelvic Nodal Radiation Therapy in Patients With High-Risk Prostate Cancer. [2021]

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

Image-guided hypofractionated radiotherapy in low-risk prostate cancer patients. [2021]

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

Moderate Hypofractionation in Intermediate- and High-Risk, Localized Prostate Cancer: Health-Related Quality of Life From the Randomized, Phase 3 HYPRO Trial. [2019]