PSMA Radioligand Therapy for Prostate Cancer

Recruiting at 2 trial locations

Overseen By Maya Aslam

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must be taking: Lutetium PSMA-targeted RLT

Disqualifiers: Bleeding disorders, Imaging intolerance, others

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 6 months

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores why some prostate cancer patients don't respond to a specific Lutetium-based therapy targeting prostate-specific membrane antigen (PSMA). The researchers aim to understand resistance mechanisms to improve and personalize treatment. Participants will undergo several cycles of Lutetium-based PSMA radioligand therapy, with scans and biopsies to gather data. Those with prostate cancer who are starting PSMA-targeted treatment and have new or changing cancer spots suitable for biopsy might be a good fit. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in personalized cancer therapy.

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

If you are taking warfarin, aspirin, or other blood thinners, you may need to stop them for at least five days before a biopsy. You might switch to a different blood thinner during this time, but this should be approved by your doctor.

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

Research has shown that Lutetium-based PSMA therapy is generally safe for patients. In earlier studies, the most common side effects included fatigue, dry mouth, and nausea. These effects were usually mild and did not interfere with daily activities. Serious side effects, such as a very low red blood cell count, were rare.

The treatment has been well-tolerated even with long-term use. Some patients might experience dizziness or headaches soon after starting the treatment, but these symptoms typically occur within the first ten days and tend to resolve on their own. Overall, Lutetium-based PSMA therapy is considered a safe option for individuals with advanced prostate cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about lutetium-based PSMA radioligand therapy because it targets prostate-specific membrane antigen (PSMA) on prostate cancer cells, delivering radiation directly to the cancer while sparing healthy tissue. Unlike traditional treatments like chemotherapy or hormone therapy that affect the entire body, this therapy is more precise, potentially leading to fewer side effects. Additionally, it's designed to treat prostate cancer that's resistant to other forms of treatment, offering hope for patients with limited options.

What evidence suggests that Lutetium-based PSMA Radioligand Therapy could be effective for prostate cancer?

Research has shown that Lutetium-based PSMA radioligand therapy, which participants in this trial will undergo, can help treat advanced prostate cancer. Studies have found that this treatment outperforms standard therapies, with many patients responding positively. For instance, some studies reported that up to 60% of patients had a good response. This therapy targets cancer cells by delivering radiation directly to cells with PSMA, a protein often found in prostate cancer. Additionally, the treatment is usually well-tolerated, with fewer severe side effects compared to other treatments. ^{2 4 6 7 8}

Who Is on the Research Team?

Thomas Hope, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Inclusion Criteria

Initiating treatment with Lutetium based PSMA-targeted RLT.

Participants must have a PSMA-avid lesion that is accessible to biopsy. Biopsy of newly emerging radiographic metastases is desired and preferable to the biopsy of previously existing lesions whenever possible. Newly emerging lesions are defined as those that are absent on a previous scan, or those demonstrating unequivocal progression since initiation of the last treatment. Biopsies will be performed according to local institutional standards.

Patients on warfarin, aspirin, or other anti-coagulants are eligible provided they are deemed able to tolerate discontinuation of anti-coagulation for at least five days prior to the biopsy. Conversion to low molecular weight heparin prior to biopsy is permitted per local standard operating procedures, provided there is approval by the interventional radiologist or the PI.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo PSMA-targeted radioligand therapy with at least four cycles of treatment planned, including SPECT/CT imaging after the first and fourth treatments, and a tumor biopsy and blood draw prior to the first treatment

Up to 6 months

SPECT/CT after 1st and 4th treatments, biopsy and blood draw prior to 1st treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, with optional biopsy and blood draw at time of progression

Up to 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Blood Draw
• Lutetium-based PSMA Radioligand Therapy
• Single-photon emission computed tomography
• Tumor Biopsy

How Is the Trial Designed?

Group I: Participants undergoing 177Lu-PSMA-617 treatment Experimental Treatment 3 Interventions

Participants undergoing PSMA targeted radioligand therapy with at least four cycles of treatment planned will undergo the following: SPECT/CTs will be performed 24 hours after the first treatment and after the fourth treatment, a tumor biopsy will be performed prior to the first 177Lu-PSMA radioligand therapy, a blood will be drawn prior to treatment for future research, and an optional tumor biopsy and blood draw for future research, may also be obtained at time of progression.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Prostate Cancer Foundation

Collaborator

Trials

52

Recruited

3,000+

Citations

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

Lutetium-177–PSMA-617 for Metastatic Castration ... Lutetium-177 ( 177 Lu)–PSMA-617 is a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment.

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

Safety and Efficacy of Lutetium-177 PSMA Therapy for ... When combined with standard therapy, lutetium-177 PSMA-617 is well tolerated and more effective than standard treatment alone in patients with advanced PSMA- ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7005080/

Clinical outcome of standardized 177Lu-PSMA-617 ... [177Lu]Lu-PSMA-617 radio-ligand therapy (PSMA-RLT) is emerging in patients with an advanced metastatic castration-resistant prostate cancer (mCRPC).

4. jnm.snmjournals.org jnm.snmjournals.org/content/62/supplement_1/1311

Efficacy and safety of Lutetium-177 PSMA radioligand therapy ... According to RECIST 1.1, the best objective response rate was 60% (95% CI: 23.1%-88.2%) in the 177Lu-PSMA arm versus 40% (95% CI: 16.8%-68.7%) ...

5. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(24)01653-2/abstract

177Lu-PSMA-617 versus a change of androgen receptor ... The incidence of grade 3–5 adverse events was lower in the 177Lu-PSMA-617 group (at least one event in 81 [36%] of 227 patients; four [2%] grade ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12481865/

Adverse events associated with Lutetium-177-PSMA-617 ... 6) suggesting that neurologic adverse events—such as headache, dizziness, or syncope—tend to occur predominantly within the first ten days after ...

7. jnm.snmjournals.org jnm.snmjournals.org/content/65/6/909

Safety and Efficacy of Extended Therapy with [177Lu]Lu-PSMA Extended treatment with [177Lu]Lu-PSMA was well tolerated, with few grades 3–4 adverse events, with the most frequent being anemia after 6 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4914299/

Therapeutic response and side effects of repeated ... These results confirmed that Lu-PSMA is a safe treatment option for metastatic PC patients and has a low toxicity profile. A positive response to therapy in ...