Radiotherapy Techniques for Prostate Cancer

Overseen By Sandy Chang

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Scott Tyldesley

Disqualifiers: Indwelling catheter, Hip prosthesis, Metastatic 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

Compensation: Varies

Number of Visits: 20

104 Participants Needed

Trial Summary

What is the purpose of this trial?

The study is being done to compare the side effects between two different radiation techniques, standard non-adaptive radiation therapy vs. daily adaptive radiation therapy and also comparing two different bladder filling instructions to find out if customized bladder instructions may lead to better treatment outcomes.

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 the drug sacituzumab govitecan (Trodelvy) for treating prostate cancer?

Sacituzumab govitecan has shown effectiveness in treating various solid tumors, including breast cancer and small cell lung cancer, by targeting a protein called Trop-2 on cancer cells and delivering a cancer-fighting agent called SN-38. While it is being explored for prostate cancer, its success in other cancers suggests potential benefits. ^{1 2 3 4 5}

Is adaptive radiotherapy safe for treating prostate cancer?

Adaptive radiotherapy for prostate cancer has shown to reduce side effects to nearby organs by adjusting radiation delivery to daily changes in anatomy. In a small case series, patients experienced acceptable short-term side effects, but longer-term safety data is not yet available. ^{6 7 8 9 10}

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

Adaptive radiotherapy is unique because it adjusts the treatment plan based on daily changes in the patient's anatomy, which can improve targeting of the cancer and reduce damage to surrounding healthy tissues. This approach is different from traditional methods that use a fixed plan throughout the treatment course. ^{9 11 12 13 14}

Eligibility Criteria

This trial is for individuals with intermediate or high risk localized prostate cancer. Specific eligibility criteria are not provided, but typically participants would need to meet certain health standards and have no conditions that could interfere with the study.

Inclusion Criteria

Willing and able to have regular per protocol follow up and blood work

Nodal risk ≥ 20% using the Memorial Sloan Kettering Nodal Risk Nomogram

Able to complete BC Cancer POSI questionnaires

Exclusion Criteria

Any other serious intercurrent illness or medical condition judged by the local investigator to compromise the participant's safety, preclude safe administration of the planned protocol treatment, or prevent the participant from being managed according to the protocol guidelines

I have had radiation therapy to my pelvic area before.

I have had surgery for prostate cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Treatment

Participants receive either adaptive or non-adaptive radiotherapy with standard or custom bladder filling instructions

4 weeks

20 fractions

Follow-up

Participants are monitored for safety and effectiveness after treatment using patient-reported and physician-reported questionnaires

5 years

Treatment Details

Interventions

• Adaptive Radiotherapy
• Non-adaptive Radiotherapy

Trial Overview The study compares side effects of two radiation techniques: standard non-adaptive therapy versus daily adaptive therapy. It also examines if customized bladder filling instructions improve treatment outcomes for prostate cancer patients.

Participant Groups

Group I: Arm 1i Active Control 1 Intervention

Adaptive RT \& Standard Bladder Filling Instructions

Group II: Arm 1ii Active Control 1 Intervention

Adaptive RT and Custom Bladder Filling Instructions

Group III: Arm 2i Active Control 1 Intervention

Non Adaptive RT and Standard Bladder Filling Instructions

Group IV: Arm 2ii Active Control 1 Intervention

Non Adaptive RT and Custom Bladder Filling Instructions

Adaptive Radiotherapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Trodelvy for:

• Metastatic triple-negative breast cancer (mTNBC)
• Metastatic hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer
• Metastatic urothelial cancer (approval being withdrawn)

Approved in European Union as Trodelvy for:

• Metastatic triple-negative breast cancer (mTNBC)
• Metastatic urothelial cancer

Approved in Canada as Trodelvy for:

• Metastatic triple-negative breast cancer (mTNBC)
• Metastatic urothelial cancer

Who Is Running the Clinical Trial?

Scott Tyldesley

Lead Sponsor

Trials

1

Recruited

100+

Findings from Research

Sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2, showed promising therapeutic activity in a phase I trial with 25 patients suffering from various metastatic solid cancers, achieving partial responses in two patients and stable disease in 16 others.

The maximum tolerated dose was determined to be 12 mg/kg for the first cycle, with lower doses (8 and 10 mg/kg) being safer for extended treatment, leading to acceptable toxicity levels and disease control for up to 36 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Starodub, AN., Ocean, AJ., Shah, MA., et al.[2022]

Sacituzumab govitecan (IMMU-132) demonstrated a predictable pharmacokinetic profile and manageable toxicity in patients with advanced epithelial cancers, with doses of 8 mg/kg (n=81) and 10 mg/kg (n=97) showing safety and efficacy.

The treatment resulted in objective responses in various cancer types, particularly metastatic triple-negative breast cancer, supporting the use of the 10 mg/kg dose for future clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Ocean, AJ., Starodub, AN., Bardia, A., et al.[2018]

In a study of 50 patients with metastatic small cell lung cancer (mSCLC) who had been heavily pretreated, sacituzumab govitecan demonstrated a 14% objective response rate, with 60% of patients showing tumor shrinkage, indicating its potential efficacy as a treatment option.

The treatment was found to be generally safe, with manageable side effects; however, significant adverse events included neutropenia (34%) and fatigue (13%). This suggests that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. Gray, JE., Heist, RS., Starodub, AN., et al.[2022]

Sacituzumab govitecan (SG) is an FDA-approved antibody-drug conjugate that has shown significant efficacy in treating metastatic triple-negative breast cancer, improving health-related quality of life and prolonging progression-free and overall survival in patients who have undergone multiple prior therapies.

Ongoing clinical trials are exploring the potential of SG for broader applications, including neoadjuvant and adjuvant therapies, combinations with immunotherapy, and treatment of various solid tumors, indicating its promise as a versatile cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of sacituzumab govitecan in solid tumors. Veeraballi, S., Khawar, Z., Aslam, HM., et al.[2023]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and delivers a topoisomerase I inhibitor, showing promise in treating metastatic triple-negative breast cancer (mTNBC) after at least two prior therapies.

In April 2020, it received accelerated approval in the USA for mTNBC, and it is currently undergoing further clinical trials for various cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. Syed, YY.[2021]

The RTOG 3505 study is investigating the effectiveness of combining concurrent chemoradiation with the immune checkpoint inhibitor nivolumab in patients with locally advanced non-small-cell lung cancer, aiming to improve overall survival and progression-free survival.

With a planned enrollment of 660 patients, the study is designed to have sufficient power to detect significant differences in survival outcomes, ensuring robust results regarding the efficacy of nivolumab compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Design and Rationale for a Randomized Trial of Cisplatin and Etoposide Plus Thoracic Radiotherapy Followed by Nivolumab or Placebo for Locally Advanced Non-Small-Cell Lung Cancer (RTOG 3505). Gerber, DE., Urbanic, JJ., Langer, C., et al.[2018]

Daily adaptive radiation therapy (ART) for non-small cell lung cancer (NSCLC) can effectively reduce lung exposure while maintaining adequate coverage of the tumor target volume, as shown in a study involving 13 patients and various treatment planning scenarios.

The study found that ART allows for dose escalation to the tumor without increasing the risk of damage to surrounding healthy tissues, suggesting a potential for improved local tumor control while minimizing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric benefits of adaptive radiation therapy for patients with stage III non-small cell lung cancer. Hoppen, L., Sarria, GR., Kwok, CS., et al.[2023]

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]

References

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

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. [2022]

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

Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. [2018]

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

Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Role of sacituzumab govitecan in solid tumors. [2023]

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

Sacituzumab Govitecan: First Approval. [2021]

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

Adaptive radiation therapy in head and neck cancer for clinical practice: state of the art and practical challenges. [2022]

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

Treatment Design and Rationale for a Randomized Trial of Cisplatin and Etoposide Plus Thoracic Radiotherapy Followed by Nivolumab or Placebo for Locally Advanced Non-Small-Cell Lung Cancer (RTOG 3505). [2018]

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

Dosimetric benefits of adaptive radiation therapy for patients with stage III non-small cell lung cancer. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Adaptive radiotherapy in the radiation salvage of prostate cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Novel approaches of chemoradiotherapy in unresectable stage IIIA and stage IIIB non-small cell lung cancer. [2021]

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

Adaptive radiation therapy strategies in the treatment of prostate cancer patients using hypofractionated VMAT. [2023]

12. France pubmed.ncbi.nlm.nih.gov

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

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

Current standards and future directions for prostate cancer radiation therapy. [2013]

14. Italy pubmed.ncbi.nlm.nih.gov

Techniques for adaptive prostate radiotherapy. [2017]