Radiotherapy vs Chemotherapy for Prostate Cancer

Not currently recruiting at 10 trial locations

Overseen By Wendy Parulekar

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must be taking: LHRH agonist/antagonist

Must not be taking: Chemotherapy, Radio-immunotherapy

Disqualifiers: Brain metastases, Cardiac 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: 12

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new radiation treatment called 177Lu PSMA 617 (also known as Pluvicto or Lutetium Lu 177-PSMA-617) to determine if it can slow prostate cancer more effectively than standard chemotherapy. Researchers aim to find out if this treatment can target cancer more precisely and control it more effectively. The trial is for men with prostate cancer that has spread and is unresponsive to standard hormone treatments. Participants should have previously tried prostate cancer drugs like abiraterone or enzalutamide without success. This trial offers an opportunity to potentially try a cutting-edge treatment that might better manage their cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, providing a chance to benefit from an innovative approach.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it does require that you have progressed on treatment with certain prostate cancer medications like abiraterone or enzalutamide.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that 177Lu-PSMA-617 is generally well-tolerated by patients. A previous study examined the treatment's safety alongside standard care, focusing on long-term safety and side effects. While some side effects occurred, most patients managed the treatment well.

For docetaxel, studies have indicated it can cause side effects, including hospitalization in about 34% of patients and febrile neutropenia, a fever with low white blood cells. Healthcare providers monitor these known effects.

Both treatments have been studied for safety. 177Lu-PSMA-617 has shown promising results in being manageable, and docetaxel has a well-documented safety profile. Patients should consult their doctors to understand what these findings might mean for them personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Most treatments for prostate cancer, like chemotherapy with drugs such as Docetaxel, work by attacking rapidly dividing cancer cells throughout the body, but they can also affect healthy cells, leading to side effects. However, 177Lu-PSMA-617 offers a more targeted approach. This treatment uses a radioactive molecule that specifically binds to the PSMA protein found on prostate cancer cells. By delivering radiation directly to the cancer, it aims to minimize damage to healthy cells. Researchers are excited about this potential for precision, hoping it will lead to fewer side effects and improved outcomes for patients.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

This trial will compare the effectiveness of two treatments for prostate cancer: 177Lu-PSMA-617 and Docetaxel. Studies have shown that 177Lu-PSMA-617 can slow prostate cancer growth. In one study, patients receiving 177Lu-PSMA-617 lived longer without cancer progression—about 8.7 months compared to 3.4 months for those who did not receive it. This treatment targets prostate cancer cells and delivers radiation directly to them, aiding in the destruction of cancer cells.

Docetaxel, which participants in this trial may also receive, is another effective treatment for prostate cancer. It is a type of chemotherapy that can reduce the risk of death in prostate cancer patients. Research has shown it to be a manageable and highly effective treatment, particularly for those with hormone-sensitive metastatic prostate cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Kim Chi

Principal Investigator

BCCA - Vancouver Cancer Centre, BC Canada

Francois Benard

Principal Investigator

BCCA - Vancouver Cancer Centre, BC Canada

Fred Saad

Principal Investigator

CHUM-Centre Hospitalier de l'Universite de Montreal, Canada

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has spread, showing progression despite treatment with drugs like abiraterone or enzalutamide. They must have PSMA-positive cancer confirmed by PET imaging, be in fairly good health (ECOG 0-2), and have recovered from previous treatments. Excluded are those who've had certain prior therapies including 177Lu-PSMA, recent major surgery, uncontrolled medical conditions, brain metastases, or severe allergies to study drugs.

Inclusion Criteria

My condition worsened despite treatment with specific prostate cancer medications.

My prostate cancer diagnosis was confirmed by a tissue sample and does not include small cell cancer.

My scans show PSMA positive metastatic disease using specific tracers.

Exclusion Criteria

You have had an allergic reaction to the study drug or its components in the past.

I've had chemotherapy for hormone-resistant cancer or within a year for hormone-sensitive cancer.

I have not had major surgery in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 177Lu-PSMA-617 or docetaxel chemotherapy

36 weeks

12 visits (in-person, every 3 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-PSMA-617
• Docetaxel

Trial Overview This trial is testing whether a new targeted radiation therapy called 177Lu PSMA-617 can slow the growth of prostate cancer more effectively than the standard chemotherapy drug Docetaxel. Patients will receive either the experimental therapy or standard chemotherapy to compare effectiveness.

How Is the Trial Designed?

Group I: 177 Lu-PSMA-617 Experimental Treatment 1 Intervention

Group II: Docetaxel Active Control 1 Intervention

177Lu-PSMA-617 is already approved in United States, European Union for the following indications:

Approved in United States as Pluvicto for:

• Metastatic castration-resistant prostate cancer

Approved in European Union as Pluvicto for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Prostate Cancer Canada

Collaborator

Trials

10

Recruited

7,500+

Endocyte

Industry Sponsor

Trials

36

Recruited

3,400+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In a phase 2 trial involving 40 chemotherapy-naïve patients with metastatic castration-resistant prostate cancer, the PSMA inhibitor [177Lu]Lu-PSMA-617 showed comparable overall survival (OS) to docetaxel, with a median OS of 15.0 months for both treatments in intention-to-treat analysis.

The per-protocol analysis indicated a median OS of 19.0 months for [177Lu]Lu-PSMA-617 compared to 15.0 months for docetaxel, suggesting that [177Lu]Lu-PSMA-617 may offer improved outcomes when administered earlier in treatment, although no significant differences were found between the two therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-PSMA-617 Versus Docetaxel in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: Final Survival Analysis of a Phase 2 Randomized, Controlled Trial. Satapathy, S., Mittal, BR., Sood, A., et al.[2023]

The FDA approved Pluvicto (177Lu-PSMA-617) for treating metastatic castration-resistant prostate cancer (mCRPC) in patients who have undergone prior treatments, showing a significant improvement in overall survival (15.3 months vs. 11.3 months with standard care) in a trial with 831 participants.

Common side effects of Pluvicto include fatigue, dry mouth, and nausea, with notable laboratory abnormalities such as decreased lymphocytes and hemoglobin occurring in over 30% of patients, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. Fallah, J., Agrawal, S., Gittleman, H., et al.[2023]

[177Lu]Lu-PSMA-617 (PluvictoTM) is an FDA-approved treatment for prostate cancer specifically for patients with PSMA-positive metastatic castration-resistant prostate cancer who have already undergone other therapies.

This treatment uses a targeted radioligand therapy that delivers radiation directly to tumor cells, effectively killing them while minimizing damage to healthy tissue, as shown in multiple clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-PSMA-617 (PluvictoTM): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer. Hennrich, U., Eder, M.[2022]

The UpFrontPSMA trial is evaluating the effectiveness and safety of combining lutetium-177 (177 Lu)-PSMA-617 with docetaxel in 140 men with newly diagnosed metastatic hormone-naïve prostate cancer, aiming to determine the proportion of patients achieving undetectable PSA levels after 12 months.

This study is significant as it compares the experimental treatment to standard docetaxel therapy while all patients receive continuous androgen deprivation therapy, potentially providing insights into improved treatment strategies for this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UpFrontPSMA: a randomized phase 2 study of sequential 177 Lu-PSMA-617 and docetaxel vs docetaxel in metastatic hormone-naïve prostate cancer (clinical trial protocol). Dhiantravan, N., Emmett, L., Joshua, AM., et al.[2021]

In a study involving 40 chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC), Lutetium-177 PSMA-617 showed a best prostate-specific antigen response rate of 60%, compared to 40% for docetaxel, demonstrating its efficacy as a treatment option.

177Lu-PSMA-617 was associated with fewer severe adverse events and significantly improved quality of life compared to docetaxel, suggesting it may be a safer alternative that could be used earlier in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial. Satapathy, S., Mittal, BR., Sood, A., et al.[2022]

The VISION trial demonstrated that Lutetium-177[177Lu]Lu-PSMA-617 significantly improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy, marking a breakthrough in treatment options.

Both the VISION and TheraP trials showed that [177Lu]Lu-PSMA-617 has a favorable safety profile, with common side effects including fatigue and nausea, suggesting it could be beneficial even for patients who have undergone extensive prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617: A Vision of the Future. Chandran, E., Figg, WD., Madan, R.[2022]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2107322

Lutetium-177–PSMA-617 for Metastatic Castration ... Lu-PSMA-617 plus standard care significantly prolonged, as compared with standard care, both imaging-based progression-free survival (median, 8.7 vs. 3.4 months ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40752988/

Outcomes for [ 177 Lu]Lu-PSMA-617 with and Without ... Key findings and limitations: Among 256 patients, 106 (41.4%) received an ARPI with [177Lu]Lu-PSMA-617. Those receiving an ARPI had lower ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251559

Overall survival of prostate cancer patients treated with Lu-177 ... Median overall survival was found to be approximately 4 months higher than OS reported in VISION trial and equal to that in TheraP trial.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.97

Real world outcomes of 177 Lu-PSMA-617 ... The cohort completed a median number of 4 cycles of 177Lu-PSMA-617; 35.7% completed six cycles. The overall cohort had a 12-month survival of ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1558767325000989

Safety and Efficacy of Lutetium-177 PSMA Therapy for ... [177Lu]Lu-PSMA-617 is a radioactive drug that binds to PSMA and delivers radiation directly to prostate cancer cells. This can kill the cancer cells while ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS294

Long-term safety outcomes of 177Lu-PSMA-617 in patients ... It is important to further characterize long-term safety outcomes in 177 Lu-PSMA-617–treated patients, with particular regard to potential treatment-related ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00852-X/fulltext

Final overall survival and safety analyses of the phase III ... At the time of the final OS analysis, 299 deaths were reported in 142/234 participants (60.7%) in the 177Lu-PSMA-617 arm and 157/234 (67.1%) in ...