Radiotherapy vs Chemotherapy for Prostate Cancer

Recruiting at 9 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

200 Participants Needed

Trial Summary

What is the purpose of this trial?

177Lu PSMA 617 is a new type of therapy which is designed to deliver high doses of radiation directly to prostate cancer sites in the body. The purpose of this study is to find out whether 177Lu PSMA 617can slow the growth of prostate cancer compared to standard chemotherapy treatment

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.

What data supports the effectiveness of the drug 177Lu-PSMA-617 for prostate cancer?

The drug 177Lu-PSMA-617 has been shown to improve overall survival in patients with prostate cancer, particularly those with PSMA-positive metastatic castration-resistant prostate cancer, as demonstrated in clinical trials. It was found to be as effective as docetaxel, a standard chemotherapy drug, in achieving a biochemical response in patients who had not previously received chemotherapy. ^{1 2 3 4 5}

Is 177Lu-PSMA-617 safe for humans?

177Lu-PSMA-617, also known as Pluvicto, has been shown to have a good safety profile in clinical trials, with common side effects including tiredness, nausea, dry mouth, reduced blood cell production, and diarrhea. It has been approved by the FDA for certain prostate cancer patients, indicating it is generally considered safe for use in humans. ^{1 2 3 4 6}

How is the drug 177Lu-PSMA-617 different from other prostate cancer treatments?

177Lu-PSMA-617 is unique because it is a radioligand therapy that specifically targets prostate cancer cells by delivering radiation directly to them, minimizing damage to healthy tissue. This approach is different from traditional chemotherapy, which affects both cancerous and healthy cells, and it has shown promising results in patients who have already undergone other treatments. ^{1 3 4 5 6}

Research Team

Francois Benard

Principal Investigator

BCCA - Vancouver Cancer Centre, BC Canada

Fred Saad

Principal Investigator

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

Kim Chi

Principal Investigator

BCCA - Vancouver Cancer Centre, BC Canada

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

[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 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]

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]

References

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

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

2. England 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). [2021]

3. United States 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. [2023]

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

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. [2023]

5. Germany 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. [2022]

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

Lutetium-177-PSMA-617: A Vision of the Future. [2022]