Relugolix + Radiation Therapy for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Kansas Medical Center

Must be taking: Androgen deprivation

Must not be taking: Anti-neoplastic agents

Disqualifiers: Psychiatric illness, Active infection, 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

Compensation: Varies

Number of Visits: 1

Duration: 12-24 months

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial evaluates the best duration for relugolix to be given in combination with radiation therapy when treating patients with high risk prostate cancer. Prostate cancer is a hormonal influenced cancer. Part of the usual treatment for patients with prostate cancer is androgen deprivation therapy (ADT). ADT is used to lower the amount of testosterone in the body, because testosterone appears to help prostate cancer grow. Relugolix works to reduce testosterone levels, which may inhibit proliferation of prostate cancer cells. It is approved by the Food and Drug Administration to treat prostate cancer. Adding relugolix to standard radiation therapy might work better and have fewer side effects than prior forms of hormonal therapy, but the optimal duration of relugolix in combination with radiation is not known.

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 you cannot use other cancer treatments while participating. If you're on androgen deprivation therapy, your testosterone levels must be above 50 ng/dL, and bicalutamide at 50 mg/daily or less is allowed.

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

Research suggests that image-guided radiotherapy (IGRT) combined with intensity-modulated radiotherapy (IMRT) can improve outcomes for prostate cancer patients by allowing higher radiation doses to the tumor while reducing side effects. This approach may enhance the effectiveness of the treatment for high-risk prostate cancer. ^{1 2 3 4 5}

Is the combination of Relugolix and radiation therapy safe for humans?

Research on radiation therapy, including intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), shows that these treatments can cause some side effects, like gastrointestinal (stomach and intestines) and genitourinary (urinary system) issues, but they are generally considered safe when managed properly. Relugolix, a medication used in prostate cancer treatment, has been studied separately and is also generally safe, though it may have its own side effects. Always discuss potential risks with your healthcare provider. ^{1 6 7 8 9}

How is the treatment Relugolix + Radiation Therapy for prostate cancer different from other treatments?

This treatment combines Relugolix, a drug that lowers testosterone levels, with advanced radiation techniques like image-guided radiotherapy (IGRT) to precisely target prostate cancer while minimizing damage to surrounding tissues. This approach may offer improved targeting and reduced side effects compared to traditional methods. ^{1 10 11 12 13}

Research Team

Xinglei Shen

Principal Investigator

University of Kansas

Eligibility Criteria

This trial is for men over 18 with high risk prostate cancer who can consent to the study, have a life expectancy over 5 years, and are eligible for radiation therapy combined with ADT. They must have good organ function and agree to use contraception. It's not for those in other clinical trials, using anti-cancer drugs, with severe infections or psychiatric/social limitations, allergic reactions to study drug components, current ADT (unless testosterone levels are adequate), or prior treatments that overlap with this study.

Inclusion Criteria

Hemoglobin ≥ 9 g/dL

Life expectancy > 5 years

Platelets >= 100 K/UL

Exclusion Criteria

Simultaneously enrolled in any therapeutic clinical trial

I am not using, nor plan to use, other cancer treatments during this study.

I have had surgery to remove my prostate.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive relugolix orally once daily. Cycles repeat every 3 months for 12 or 24 months, with brachytherapy and external beam radiation over 25 fractions starting 30 to 180 days after relugolix initiation.

12-24 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment. Arm A: every 3 months for 12 months, then every 6 months up to 36 months. Arm B: every 6 months up to 36 months.

Up to 36 months

Regular follow-up visits

Treatment Details

Interventions

• Radiation Therapy
• Relugolix

Trial Overview The trial is testing how long relugolix should be given alongside standard radiation therapy in treating high-risk prostate cancer. Relugolix lowers testosterone which may help slow down the growth of prostate cancer cells. The goal is to find out if adding relugolix improves outcomes and has fewer side effects than previous hormonal therapies.

Participant Groups

Group I: Arm B (relugolix, brachytherapy, external beam radiation) Experimental Treatment 10 Interventions

Patients receive relugolix PO QD. Cycles repeat every 3 months for 24 months in the absence of disease progression or unacceptable toxicity. Beginning 30 to 180 days after start of relugolix, patients undergo brachytherapy and external beam radiation over 25 fractions. Patients undergo bone scan, CT or MRI or PSMA PET scan during screening. Patients also undergo DEXA scan and may optionally undergo blood sample collection throughout the trial.

Group II: Arm A (relugolix, brachytherapy, external beam radiation) Experimental Treatment 10 Interventions

Patients receive relugolix PO QD. Cycles repeat every 3 months for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 30 to 180 days after start of relugolix, patients undergo brachytherapy and external beam radiation over 25 fractions. Patients undergo bone scan, CT or MRI or PSMA PET scan during screening. Patients also undergo DEXA scan and may optionally undergo blood sample collection throughout the trial.

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?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 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]

Intensity Modulated Radiotherapy (IMRT) allows for more precise targeting of tumors while sparing surrounding healthy tissues, making it the current standard for treating head and prostate cancers.

The integration of image-guided radiotherapy (IGRT) is crucial for addressing challenges like tumor motion and anatomical changes during treatment, ensuring better delivery of radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in radiotherapy. Bhide, SA., Nutting, CM.[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]

Prostate cancer patients receiving image-guided radiotherapy (IGRT) experienced significantly less severe acute toxicity, such as urinary frequency, diarrhoea, and fatigue, compared to those who did not receive IGRT, with 23% vs 7% for urinary frequency ≥G3 and 15% vs 3% for diarrhoea ≥G2.

The onset of these toxicities was earlier in the non-IGRT group, indicating that IGRT not only reduces the severity of symptoms but also delays their onset, leading to a more tolerable treatment experience for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy. Gill, S., Thomas, J., Fox, C., et al.[2021]

Transrectal ultrasound-guided prostate brachytherapy is the most advanced method for delivering radiation, achieving lower prostate-specific antigen (PSA) levels than other treatments like IMRT, while maintaining biochemical control in about 90% of patients.

Brachytherapy as an organ-conserving treatment results in lower rates of erectile dysfunction and urinary incontinence compared to surgery, making it a safer option for patients with low-risk prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on prostate brachytherapy: long-term outcomes and treatment-related morbidity. Kao, J., Cesaretti, JA., Stone, NN., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Potential applications of image-guided radiotherapy for radiation dose escalation in patients with early stage high-risk prostate cancer. [2020]

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

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Radiation dose escalation for localized prostate cancer: intensity-modulated radiotherapy versus permanent transperineal brachytherapy. [2022]

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

Recent advances in radiotherapy. [2022]

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

Modeling of Acute Rectal Toxicity to Compare Two Patient Positioning Methods for Prostate Cancer Radiotherapy: Can Toxicity Modeling be Used for Quality Assurance? [2022]

7. 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]

8. Thailand pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy combined with endocrine therapy for intermediate and advanced prostate cancer: long-term outcome of Chinese patients. [2019]

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

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

[Image-guided radiotherapy for prostate cancer]. [2016]

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

Update on prostate brachytherapy: long-term outcomes and treatment-related morbidity. [2022]

12. India pubmed.ncbi.nlm.nih.gov

Simple method for correcting imperfectly placed fiducial markers for image-guided radiotherapy technologies of the prostate cancer. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Rectal radiation dose-reduction techniques in prostate cancer: a focus on the rectal spacer. [2019]