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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of combining two treatments, carboplatin (a chemotherapy drug) and 177Lu-PSMA-617 (a radioligand therapy), for prostate cancer. Researchers aim to determine if this combination can shrink or halt the growth of prostate cancer. It targets men with confirmed prostate cancer that has progressed despite previous treatments like chemotherapy or hormone therapy. Participants must have at least one detectable cancerous lesion on scans and be willing to undergo a biopsy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this novel combination 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.

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

Research has shown that both 177Lu-PSMA-617 and carboplatin have been studied for their safety in treating prostate cancer. Several studies have tested 177Lu-PSMA-617, and one study found it to be generally safe and well-tolerated, with common side effects like dry mouth and tiredness, while serious side effects were rare.

Carboplatin, a chemotherapy used for various cancers including prostate cancer, is usually well-tolerated according to studies. However, patients can experience side effects such as low blood counts and tiredness, which are common in chemotherapy treatments.

As this trial is in an early phase, researchers are still testing the safety of these treatments when used together. They are closely monitoring patient responses to determine the safest dose. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of 177Lu-PSMA-617 and carboplatin for prostate cancer because it offers a novel approach by targeting prostate-specific membrane antigen (PSMA) on cancer cells. While traditional treatments like hormone therapy and chemotherapy attack cancer cells in a more general way, 177Lu-PSMA-617 delivers radiation directly to PSMA-expressing cells, potentially sparing healthy tissue. This precision could improve effectiveness and reduce side effects. Additionally, pairing it with carboplatin, a well-established chemotherapy agent, could enhance the overall impact on cancer cells, giving a one-two punch that might lead to better outcomes for patients.

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

Research has shown that 177Lu-PSMA-617 effectively treats prostate cancer. It attaches to prostate cancer cells and delivers radiation directly to them, killing these cells. Studies have found that it significantly extends the time before the cancer worsens. In this trial, participants will receive a combination of 177Lu-PSMA-617 and Carboplatin, a chemotherapy that has shown some effectiveness in treating advanced prostate cancer, especially when other treatments no longer work. It is generally well-tolerated, causing few severe side effects for most patients. Combining these two treatments might be more effective because they attack cancer cells in two different ways. ^{1 3 5 6 7}

Who Is on the Research Team?

Praful Ravi, MB BCHir, MRCP

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

[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 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]

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]

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]

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 ...