Radiation Therapy for Prostate Cancer

(FORT Trial)

Recruiting at 1 trial location

Overseen By Sharanya Chandrasekhar

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Disqualifiers: Pelvic radiotherapy, Inflammatory bowel disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 5

Duration: 1-2 weeks

136 Participants Needed

Trial Summary

What is the purpose of this trial?

The study is a randomized study that compares 5 radiation therapy treatments to 2 radiation therapy treatments in men with low or intermediate-risk prostate cancer.

Will I have to stop taking my current medications?

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 this treatment for prostate cancer?

Radiation therapy is a valid alternative to surgery for prostate cancer, with dose-escalated radiation improving patient outcomes. Techniques like intensity-modulated radiation therapy (IMRT) and stereotactic body radiotherapy (SBRT) have shown promise in improving local control and reducing side effects. ^{1 2 3 4 5}

Is radiation therapy generally safe for prostate cancer treatment?

Research shows that advanced radiation therapy techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) are generally safe, with some patients experiencing mild to moderate side effects such as gastrointestinal (GI) and genitourinary (GU) issues. The use of these techniques can reduce the risk of side effects compared to older methods. ^{6 7 8 9 10}

How is radiation therapy unique for treating prostate cancer?

Radiation therapy for prostate cancer, especially with advanced techniques like intensity-modulated radiation therapy (IMRT) and image-guided radiotherapy (IGRT), allows for higher doses of radiation to be delivered more precisely to the tumor, reducing damage to surrounding healthy tissue and potentially improving treatment outcomes compared to older methods. ^{4 11 12 13 14}

Research Team

Himanshu Nagar, M.D.

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for men over 18 with low or intermediate-risk prostate cancer, who are generally healthy and can undergo MRI-guided radiotherapy. They should not have had pelvic radiation before, no large prostate on MRI (>80 cc), no recent TURP surgery, no metastatic disease, and no history of inflammatory bowel disease or hip replacements.

Inclusion Criteria

I am fully active or can carry out light work.

I have no other diseases that could affect this cancer treatment's safety or results.

Ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire

Exclusion Criteria

MRI Prostate Volume greater than 80 cc

I have a history of inflammatory bowel disease.

I have had one or both of my hips replaced.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 5 or 2 MRI-guided adaptive radiotherapy treatments for prostate cancer

1-2 weeks

2 or 5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at multiple intervals

60 months

Regular follow-up visits at 3, 6, 12, 24, and 60 months

Treatment Details

Interventions

• Radiation Therapy

Trial Overview The study compares two different schedules of MRI-guided adaptive radiotherapy treatments for prostate cancer: one group will receive five treatments while the other group will receive just two. The goal is to see which treatment schedule works best.

Participant Groups

Group I: 5 radiation treatments - ARM 1 Experimental Treatment 1 Intervention

Patients randomized to ARM 1 will receive 37.5 in 5 radiotherapy treatments.

Group II: 2 radiation treatments - ARM 2 Active Control 1 Intervention

Patients randomized to ARM 2 will receive 25 Gy in 2 radiotherapy treatments.

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

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Progenics Pharmaceuticals, Inc.

Industry Sponsor

Trials

35

Recruited

4,400+

Viewray Inc.

Industry Sponsor

Trials

13

Recruited

1,100+

Findings from Research

Radiotherapy can be an effective curative treatment for prostate cancer, especially when patient selection is done carefully to maximize benefits.

Dose-escalated radiation and advanced imaging technologies have improved patient outcomes, and there is renewed interest in hypofractionated radiotherapy methods like stereotactic body radiotherapy and brachytherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contemporary issues in radiotherapy for clinically localized prostate cancer. Khor, R., Williams, S.[2013]

In a study of 285 patients treated with salvage radiation therapy (SRT) after prostate surgery, intensity-modulated radiation therapy (IMRT) significantly reduced the risk of late grade ≥2 gastrointestinal (GI) toxicity compared to three-dimensional conformal radiation therapy (3D-CRT), with rates of 1.9% for IMRT versus 10.2% for 3D-CRT.

While IMRT showed benefits in reducing GI toxicity, it did not significantly lower the risk of late grade ≥2 genitourinary (GU) toxicity or other complications like urinary incontinence and erectile dysfunction when compared to 3D-CRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved toxicity profile following high-dose postprostatectomy salvage radiation therapy with intensity-modulated radiation therapy. Goenka, A., Magsanoc, JM., Pei, X., et al.[2022]

Radiation therapy is an effective treatment for localized prostate cancer, but there is still a significant rate of cancer persistence after treatment, indicating a need for improved methods.

New radiation techniques are being developed to enhance local control of the cancer while also aiming to preserve bladder and sexual function, and ongoing research seeks to identify which patients will benefit most from radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The role of radiotherapy in locally limited prostate cancer]. Herr, HW.[2006]

Intensity-modulated radiation therapy (IMRT) significantly reduces the mean dose and volume of radiation received by the rectum and bladder compared to 3-dimensional conformal radiation therapy (3DCRT), which is crucial for minimizing side effects in prostate cancer treatment.

IMRT allows for dose escalation up to 72.0 Gy while maintaining similar safety profiles for the bladder and rectum compared to 3DCRT at 68.4 Gy, suggesting potential for improved treatment efficacy without increasing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential for dose escalation in the postprostatectomy setting with intensity-modulated radiation therapy: a dosimetric study using EORTC consensus guidelines for target volume contours. Harrison, A., Studenski, M., Harvey, A., et al.[2016]

Prostate cancer cells exhibit high levels of autophagy, indicated by high LC3A and low LAMP2a levels, which are associated with poorer outcomes in patients treated with radical radiotherapy.

Blocking components of the autophagy pathway can increase the sensitivity of prostate cancer cells to radiation, suggesting that targeting autophagy may enhance the effectiveness of radiotherapy in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensified autophagy compromises the efficacy of radiotherapy against prostate cancer. Koukourakis, MI., Kalamida, D., Mitrakas, A., et al.[2022]

In a study of 192 patients with localized prostate cancer, using prostate-based IGRT (P-IGRT) resulted in significantly lower acute gastrointestinal toxicities compared to bony structure-based IGRT (B-IGRT), with rates of 3% versus 11%.

Both P-IGRT and B-IGRT showed similar prostate-specific antigen failure-free survival rates at 3 years (95.5% for P-IGRT and 92.7% for B-IGRT), indicating that P-IGRT can reduce toxicity without compromising tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance. Nakamura, K., Mizowaki, T., Inokuchi, H., et al.[2018]

Patients with high-risk prostate cancer treated with image-guided intensity-modulated radiotherapy (IG-IMRT) experienced significantly lower rates of gastrointestinal (GI) toxicity (5.8%) compared to those treated with 3D conformal radiotherapy (3DCRT) (57.3%), indicating that IG-IMRT is a safer option.

Both IG-IMRT and 3DCRT showed similar rates of biochemical progression-free survival at 3 years (90.3% for IG-IMRT vs. 86.0% for 3DCRT), suggesting that while IG-IMRT reduces toxicity, it does not compromise treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance. Sveistrup, J., af Rosenschöld, PM., Deasy, JO., et al.[2021]

In a study of 421 patients undergoing salvage radiotherapy (SRT) after prostate surgery, the use of advanced techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) significantly reduced the incidence of late gastrointestinal (GI) toxicities to 4.8%.

However, increasing the radiation dose to 68 Gy or more was linked to a higher risk of genitourinary (GU) toxicities, indicating that while advanced techniques can help minimize some side effects, higher doses may still pose risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. Tomita, N., Uchiyama, K., Mizuno, T., et al.[2021]

In a study of 100 prostate cancer patients treated with high-dose intensity-modulated radiotherapy (IMRT) and image-guided treatment (IGRT), acute gastrointestinal (GI) toxicity was observed in 12% and genitourinary (GU) toxicity in 42%, with only 4% experiencing severe GU toxicity (grade 3).

After a median follow-up of 26 months, late toxicity rates were low, with only 1.5% experiencing late GI toxicity and 7.7% experiencing late GU toxicity, indicating that high-dose radiotherapy is both effective and has manageable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity after intensity-modulated, image-guided radiotherapy for prostate cancer. Guckenberger, M., Ok, S., Polat, B., et al.[2022]

Intensity-modulated radiation therapy (IMRT) resulted in significantly lower rates of acute and late genitourinary (GU) and gastrointestinal (GI) toxicity compared to (125)I seed implants, with 3-year rates of 3.5% GU and 2.4% GI toxicity for IMRT versus 19.2% GU and 7.7% GI for (125)I.

Both treatments showed similar biochemical failure rates, with IMRT having a 4-year freedom from failure rate of 99.5% compared to 93.5% for (125)I, indicating that while both are effective, IMRT may be safer with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of acute and chronic toxicity for men with low-risk prostate cancer treated with intensity-modulated radiation therapy or (125)I permanent implant. Eade, TN., Horwitz, EM., Ruth, K., et al.[2022]

Radiotherapy is as effective as radical prostatectomy for localized prostate cancer when administered at sufficient doses, with various modalities like interstitial brachytherapy and external beam radiotherapy available.

Advancements such as intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) allow for higher radiation doses while reducing toxicity, and combining radiotherapy with hormonal ablation enhances local control rates in specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy in prostate cancer]. Ganswindt, U., Belka, C.[2021]

Radiotherapy is effective for treating prostate cancer, but it requires high doses due to the tumor's limited sensitivity to radiation.

Brachytherapy, once thought to be less effective, is now recognized as a suitable treatment option for prostate cancer, thanks to advancements in technology that allow for high-dose delivery with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radical radiotherapy of prostate carcinoma]. Kulhavý, M., Kindlová, E., Kovarík, J.[2006]

Prostate cancer treatment has advanced significantly from traditional 2D radiotherapy to more precise methods like intensity-modulated radiation therapy (IMRT) and stereotactic radiotherapy, enhancing treatment efficacy and reducing side effects.

Emerging techniques such as proton therapy and carbon therapy are being explored to further improve treatment outcomes, shorten treatment times, and minimize toxicity and costs for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[What is the level of evidence of new techniques in prostate cancer radiotherapy?]. Khadige, M., Peiffert, D., Supiot, S.[2018]

Recent advancements in radiation therapy for prostate cancer, such as intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT), have improved treatment precision, leading to reduced side effects and the ability to safely increase radiation doses.

Low dose rate (LDR) and high dose rate (HDR) brachytherapy are effective treatment options for localized prostate cancer, each with unique side effect profiles, while the potential benefits of proton therapy and stereotactic radiotherapy require further research through prospective trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Localized prostate cancer: Radiotherapeutic concepts]. Grimm, M., Wenz, F.[2018]

References

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

Contemporary issues in radiotherapy for clinically localized prostate cancer. [2013]

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

Improved toxicity profile following high-dose postprostatectomy salvage radiation therapy with intensity-modulated radiation therapy. [2022]

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

[The role of radiotherapy in locally limited prostate cancer]. [2006]

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

Potential for dose escalation in the postprostatectomy setting with intensity-modulated radiation therapy: a dosimetric study using EORTC consensus guidelines for target volume contours. [2016]

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

Intensified autophagy compromises the efficacy of radiotherapy against prostate cancer. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance. [2018]

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

Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance. [2021]

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

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Toxicity after intensity-modulated, image-guided radiotherapy for prostate cancer. [2022]

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

A comparison of acute and chronic toxicity for men with low-risk prostate cancer treated with intensity-modulated radiation therapy or (125)I permanent implant. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

[Radiotherapy in prostate cancer]. [2021]

12. Czech Republic pubmed.ncbi.nlm.nih.gov

[Radical radiotherapy of prostate carcinoma]. [2006]

13. France pubmed.ncbi.nlm.nih.gov

[What is the level of evidence of new techniques in prostate cancer radiotherapy?]. [2018]

14. Germany pubmed.ncbi.nlm.nih.gov

[Localized prostate cancer: Radiotherapeutic concepts]. [2018]