Carboplatin + 177Lu-PSMA-617 for Prostate Cancer

Recruiting at 2 trial locations

Overseen By Praful Ravi, MB BCHir, MRCP

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must be taking: LHRH/GnRH agonists

Must not be taking: Investigational agents

Disqualifiers: Untreated brain metastases, others

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

Compensation: Varies

Number of Visits: 3

37 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to see whether the combination of a chemotherapy drug, carboplatin, along with the radioligand treatment, 177Lu-PSMA-617, is safe in treating prostate cancer and whether the combination is effective in shrinking or preventing growth of prostate cancer. The names of the study drugs used in this research study are: * Carboplatin (A type of chemotherapy) * 177Lu-PSMA-617 (A type of radioligand therapy)

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy or radiotherapy within 4 weeks before starting the study treatment, and you must not be on any other investigational agents.

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

The drug 177Lu-PSMA-617 has been shown to improve survival in patients with advanced prostate cancer, with studies indicating a significant increase in overall survival compared to standard care. It works by delivering targeted radiation to cancer cells, reducing tumor size while sparing healthy tissue. ^{1 2 3 4 5}

Is the combination of Carboplatin and 177Lu-PSMA-617 safe for humans?

177Lu-PSMA-617, also known as Pluvicto, has been shown to be generally safe in humans, with common side effects including dry mouth, fatigue, nausea, and diarrhea. Serious side effects are rare and can be managed with standard medical care. ^{1 5 6 7 8}

What makes the treatment with Carboplatin and 177Lu-PSMA-617 unique for prostate cancer?

This treatment combines Carboplatin, a chemotherapy drug, with 177Lu-PSMA-617, a radioligand therapy that targets prostate-specific membrane antigen (PSMA) on cancer cells, delivering radiation directly to the tumor while sparing healthy tissue. This combination is unique because it merges traditional chemotherapy with targeted radiotherapy, potentially enhancing effectiveness against prostate cancer that has spread and is resistant to other treatments. ^{1 3 4 5 9}

Research Team

Praful Ravi, MB BCHir, MRCP

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for men with metastatic castrate-resistant prostate cancer. Participants should not have had previous chemotherapy for their condition and must be able to perform daily activities without significant assistance.

Inclusion Criteria

I agree to use effective birth control during and after the study for the required times.

I have been diagnosed with prostate cancer, mostly adenocarcinoma, based on tests or very high PSA levels.

I am willing to have a biopsy after 12 weeks of treatment.

Exclusion Criteria

I haven't had cancer treatment or experimental therapy in the last 14 days.

I am allergic to medications similar to 177Lu-PSMA-617 or carboplatin.

I haven't had chemotherapy or radiotherapy in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Phase 1A: Dose Escalation

Participants will be enrolled in a 3+3 dose escalation design to establish a maximum tolerated dose (MTD) of carboplatin, starting at Dose Level 1 and escalating to Dose Level 2 or 3.

Up to 6 cycles of 42 days each

Days 1 and 22 of each cycle, Day 2 for radioligand therapy

Phase 1B: Dose Expansion

19 additional participants will be enrolled at the RP2D of carboplatin to further assess safety and preliminary clinical activity.

Up to 6 cycles of 42 days each

Days 1 and 22 of each cycle, Day 2 for radioligand therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

Average of 1 year

In-office or via telephone

Treatment Details

Interventions

• 177Lu-PSMA-617
• Carboplatin

Trial Overview The study is testing the safety and effectiveness of combining a chemotherapy drug, Carboplatin, with a radioligand therapy called 177Lu-PSMA-617 in treating advanced prostate cancer.

Participant Groups

Group I: Phase 1B: Dose Expansion Experimental Treatment 2 Interventions

19 additional participants will be enrolled at the RP2D of carboplatin and will complete: * Baseline visit. * Day 1 of Cycles 3 and 5: Tumor assessment radiologic scans. * Tumor biopsy at baseline and at 12 weeks. * Cycle 1 through End of Treatment: * Days 1 and 22 of 42 day cycle: Predetermined dose of carboplatin every 3 weeks for a maximum of up to 6 cycles. * Day 2 of 42 day cycle: Predetermined dose of 177Lu-PSMA-617 every 6 weeks for a maximum of up to 6 cycles. * End of treatment visit. * Follow up visits in-office or via telephone.

Group II: Phase 1A: Dose Escalation Experimental Treatment 2 Interventions

Participants will be enrolled in a 3+3 dose escalation design to establish a maximum tolerated dose (MTD) of carboplatin, starting at Dose Level 1 and escalating to Dose Level 2 or 3. * Baseline visit. * Day 1 of Cycles 3 and 5: Tumor assessment radiologic scans. * Cycle 1 through End of Treatment: * Days 1 and 22 of 42-day cycle: Predetermined dose of carboplatin every 3 weeks for a maximum of up to 6 cycles. * Day 2 of 42-day cycle: Predetermined dose of 177Lu-PSMA-617 every 6 weeks for a maximum of up to 6 cycles. * End of treatment visit. * Follow up visits in-office or via telephone. If 0 out of 3 participants experience a dose-limiting toxicity (DLT), the study will proceed to the next dose level. If 1 or more participants experience a DLT, this dose level is declared the MTD and study will not proceed to expansion. If 1 out of 6 participants at the highest dose level experience DLTs, this is the recommended Phase 1B dose.

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

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]

[177Lu]Lu-PSMA-617 is effective in targeting prostate cancer, but some patients do not respond well; ongoing research is exploring combination therapies to improve outcomes for both treatment-naïve and resistant patients.

Combining [177Lu]Lu-PSMA-617 with other treatments, such as alpha radiation emitters and immune checkpoint inhibitors, shows promise in enhancing therapeutic responses, particularly for patients who have developed resistance to initial therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. Arbuznikova, D., Eder, M., Grosu, AL., et al.[2023]

177Lu-PSMA-617 therapy has shown promising efficacy in treating metastatic prostate cancer, with a majority of patients experiencing a decline in prostate-specific antigen (PSA) levels, which is associated with longer survival rates.

The analysis of 17 studies indicated that while significant toxicities were infrequent, cytopenias were noted, and factors like performance status and tumor grade were important predictors of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer. Sun, M., Niaz, MO., Nelson, A., et al.[2020]

In a phase 2 trial involving 200 men with metastatic castration-resistant prostate cancer, [177Lu]Lu-PSMA-617 showed a significantly higher prostate-specific antigen (PSA) response rate (66%) compared to cabazitaxel (37%), indicating its greater efficacy as a treatment option.

Patients receiving [177Lu]Lu-PSMA-617 experienced fewer severe adverse events (33%) compared to those on cabazitaxel (53%), suggesting a better safety profile for the radiolabeled therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Hofman, MS., Emmett, L., Sandhu, S., 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 of 50 men with advanced prostate cancer, 177Lu-PSMA-617 demonstrated a 64% rate of PSA decline of at least 50%, indicating its efficacy in targeting prostate-specific membrane antigen for treatment.

The treatment was associated with low toxicity, with common side effects being mild and self-limiting, and patients reported improved quality of life, with median overall survival reaching 13.3 months, particularly benefiting those who achieved significant PSA reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-up and Outcomes of Retreatment in an Expanded 50-Patient Single-Center Phase II Prospective Trial of 177Lu-PSMA-617 Theranostics in Metastatic Castration-Resistant Prostate Cancer. Violet, J., Sandhu, S., Iravani, A., et al.[2022]

In a study involving 64 patients with metastatic castration-resistant prostate cancer, 177Lu-PSMA-617 was found to be safe and well-tolerated, with manageable side effects such as dry mouth, fatigue, and nausea occurring in a significant number of patients.

The treatment did not lead to serious adverse events directly related to the drug, and there were no significant changes in vital signs or kidney function, suggesting a favorable safety profile for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of PSMA-Targeted Molecular Radioligand Therapy with 177Lu-PSMA-617: Results from the Prospective Multicenter Phase 2 Trial RESIST-PC (NCT03042312). Calais, J., Czernin, J., Thin, P., et al.[2023]

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]

177Lu-PSMA-617 is a promising new treatment for patients with advanced prostate cancer, specifically targeting the prostate-specific membrane antigen (PSMA) found on cancer cells.

The therapy was also experimentally applied to a female patient with metastasized leiomyosarcoma, suggesting potential for PSMA-targeted treatment in other types of tumors beyond prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. Jüptner, M., Marx, M., Zuhayra, M., et al.[2021]

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

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. [2023]

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

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer. [2020]

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

[177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. [2023]

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

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

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

Long-Term Follow-up and Outcomes of Retreatment in an Expanded 50-Patient Single-Center Phase II Prospective Trial of 177Lu-PSMA-617 Theranostics in Metastatic Castration-Resistant Prostate Cancer. [2022]

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

Safety of PSMA-Targeted Molecular Radioligand Therapy with 177Lu-PSMA-617: Results from the Prospective Multicenter Phase 2 Trial RESIST-PC (NCT03042312). [2023]

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

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

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

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. [2021]