PET Imaging for Breast Cancer

Overseen By Ahmad Shariftabrizi, M.D.

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Ahmad Shariftabrizi

Disqualifiers: Other malignancy, Pregnancy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a potential new treatment for women with metastatic triple-negative breast cancer (TNBC). Researchers use a special PET/CT scan to detect a particular protein on cancer cells that could be targeted by PSMA-based radionuclide therapy. The goal is to determine if this new approach could be an effective treatment option. Women diagnosed with metastatic TNBC who show positive results on a specific PET scan may be suitable candidates for this study. As an unphased trial, this study allows participants to contribute to groundbreaking research that could lead to new treatment options for metastatic TNBC.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this PET imaging method is safe for breast cancer patients?

Research has shown that PSMA-based radionuclide therapy looks promising. In one study, a treatment called [177Lu]Lu-PSMA-617 helped patients with advanced prostate cancer live longer. Another study found that a single dose of this treatment was safe and well-tolerated when followed by additional treatments, with no major safety issues. These results suggest that PSMA-based therapies are generally safe, but it is important to remember that each patient is different. Always consult a doctor before deciding to join a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about PSMA-based radionuclide therapy for breast cancer because it offers a new approach compared to traditional treatments like chemotherapy and hormone therapy. This therapy uses a specific molecule that targets PSMA, a protein often found in high levels in certain cancer cells, allowing for precise delivery of radiation directly to the tumor. This targeted approach not only aims to improve the effectiveness of the treatment but also minimizes damage to surrounding healthy tissue, potentially reducing side effects. By leveraging this innovative mechanism, there is hope for better outcomes in patients with challenging forms of breast cancer, such as triple-negative breast cancer.

What evidence suggests that PSMA-based radionuclide therapy might be an effective treatment for metastatic triple negative breast cancer?

Research suggests that a protein called prostate-specific membrane antigen (PSMA) might be useful in treating triple-negative breast cancer (TNBC). Although PSMA is typically associated with prostate cancer, it has shown promise in detecting and targeting cancer spread in TNBC. One study found that PSMA in TNBC tissue can be seen as clearly as with traditional imaging methods, indicating its potential usefulness in treatment. In this trial, participants will undergo PET imaging to explore PSMA-targeted approaches. Additionally, a type of therapy using PSMA has helped prostate cancer patients live longer, suggesting it might also benefit TNBC. While more direct evidence is needed for TNBC, these findings indicate that PSMA-targeted treatments could be beneficial for managing this type of breast cancer. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for women aged 18 or older with metastatic Triple Negative Breast Cancer (TNBC) confirmed by biopsy. Participants must have FDG-positive metastatic lesions visible on an initial PET/CT scan. It's not suitable for those with other active cancers, who can't tolerate a PET/CT procedure, or are pregnant/breastfeeding.

Inclusion Criteria

I am a woman aged 18 or older.

Patient should have FDG positive metastatic lesions on the initial PET/CT scan performed in this study to be further included

My initial biopsy shows that my triple-negative breast cancer has spread to distant areas.

Exclusion Criteria

Patients with any medical condition that might compromise the safety of subject during PET acquisitions

Unable to tolerate PET/CT procedure

Pregnant or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

PET Imaging

Participants undergo FDG PET/CT and 18F-DCFPyL-PET/CT imaging to evaluate PSMA expression

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PSMA-based radionuclide therapy

Trial Overview The study aims to assess the presence of Prostate Specific Membrane Antigen (PSMA) in metastatic TNBC using Fludeoxyglucose F18 (FDG) PET/CT scans as a reference. The goal is to explore PSMA-based treatments and design future trials based on these findings.

How Is the Trial Designed?

Group I: PET Imaging Experimental Treatment 1 Intervention

Triple negative breast cancer patients will undergo FDG PET/CT and Pyl PET/Ct

PSMA-based radionuclide therapy is already approved in United States, European Union for the following indications:

Approved in United States as Lutetium-177 PSMA-617 for:

• Prostate cancer

Approved in United States as 68Ga-PSMA-11 PET/CT for:

• Prostate cancer

Approved in European Union as Lutetium-177 PSMA-617 for:

• Prostate cancer

Who Is Running the Clinical Trial?

Ahmad Shariftabrizi

Lead Sponsor

Trials

1

Recruited

30+

Progenics Pharmaceuticals, Inc.

Industry Sponsor

Trials

35

Recruited

4,400+

Published Research Related to This Trial

PSMA-targeted imaging and therapy have significantly improved the management of prostate cancer, particularly in advanced stages like metastasized castration-resistant prostate cancer.

Lutetium-177-conjugated PSMA-617 or PSMA-I&T (Lu-PSMA) has shown promising results in both multicenter retrospective and monocenter prospective trials, indicating its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Cancer Theranostics: PSMA Targeted Therapy. Seifert, R., Alberts, IL., Afshar-Oromieh, A., et al.[2021]

A 76-year-old man with advanced prostate cancer showed significant improvement after treatment with lutetium 177 PSMA-617, indicating its potential efficacy in patients resistant to standard therapies.

The treatment led to marked biochemical and imaging responses, as well as improvements in clinical status and pain relief, highlighting the therapeutic benefits of PSMA-targeted nuclear medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-Prostate-specific Membrane Antigen Radioligand Therapy in Patients with Metastatic Castration-resistant Prostate Cancer. Parihar, AS., Hofman, MS., Iravani, A.[2023]

In a study of 75 patients with metastatic prostate cancer, 6 were excluded from Lutetium-177 [177Lu]-PSMA-617 treatment due to PSMA-negative/FDG-positive discordance, but 89 suitable targets for biology-guided radiotherapy (BgRT) were identified.

The research suggests that combining BgRT with Lutetium-177 [177Lu]-PSMA-617 is feasible for treating patients with discordant metastases, particularly highlighting that bone and lung metastases are the most suitable candidates for this combined therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer. Gaudreault, M., Chang, D., Hardcastle, N., et al.[2023]

In a study involving 145 patients with metastatic castration-resistant prostate cancer (mCRPC), treatment with 177Lu-PSMA-617 showed a biochemical response rate of 45%, indicating high efficacy, especially with 40% of patients responding after just one treatment cycle.

The therapy demonstrated a favorable safety profile, with only 10% of patients experiencing severe hematotoxicity and 8% reporting dry mouth, suggesting it may be a safer option compared to other third-line treatments for mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. Rahbar, K., Ahmadzadehfar, H., Kratochwil, C., et al.[2022]

Pre-clinical studies indicate that the specific activity of lutetium-177 does not significantly affect the overall tumor uptake of the PSMA-targeted radiopharmaceutical 177Lu-PSMA-617, suggesting consistent efficacy in targeting cancer cells.

However, the tumor-to-non-target organ ratios were improved with carrier added lutetium-177, indicating that while specific activity may not influence uptake, it can enhance the safety profile by reducing radiation exposure to healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo response of PSMA-617 radiolabeled with CA and NCA lutetium-177. Wieczorek Villas Boas, CA., de Jesus Silva, J., Pereira Dias, LA., et al.[2022]

177Lu PSMA-617 Radio-ligand Therapy is a promising treatment for metastatic castration-resistant prostate carcinoma, but it poses potential renal toxicity due to its excretion through the kidneys.

This case report highlights the renal safety of administering multiple doses of 177Lu PSMA-617 in a patient with a solitary-functioning kidney, suggesting that it can be safely used even in patients with compromised renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-177 Prostate Specific Membrane Antigen Therapy in a Patient With Double Malignancy and Single Functioning Kidney: A Case Report. Naeem, Z., Zahra, UB., Numair Younis, M., et al.[2023]

In a study of 135 prostate cancer patients, those with high tumor loads showed significantly reduced uptake of Ga-68-PSMA-11 in critical organs like the lacrimal and salivary glands, which could impact treatment planning for radioligand therapy (RLT).

The findings suggest that individualizing therapy protocols based on diagnostic PSMA PET imaging could enhance the efficacy and safety of Lu-177-labeled PSMA-ligand therapy, as reduced tracer uptake in dose-limiting organs may affect treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer. Gaertner, FC., Halabi, K., Ahmadzadehfar, H., et al.[2018]

In a study of seven patients with progressive prostate cancer, (177)Lu-PSMA-617 therapy was found to be safe, with the highest radiation doses absorbed by the parotid glands (1.17 mGy/MBq) and kidneys (0.88 mGy/MBq), while the bone marrow received a significantly lower dose (0.03 mGy/MBq).

The findings suggest that the parotid glands are the dose-limiting organs in this therapy, indicating that individual patient dosimetry is essential due to substantial variations in radiation absorption among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer. Kabasakal, L., AbuQbeitah, M., Aygün, A., et al.[2021]

In a study of 71 patients with metastatic castration-resistant prostate cancer, 56% experienced a significant PSA decline of 50% or more after receiving three cycles of Lutetium-177 labeled PSMA-617 radioligand therapy, indicating its efficacy as a treatment option.

The therapy demonstrated delayed responses, as 28 out of 30 patients who responded after the first cycle continued to show positive results, and 12 out of 41 initial non-responders responded to subsequent cycles, highlighting the potential for ongoing therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed response after repeated 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration resistant prostate cancer. Rahbar, K., Bögeman, M., Yordanova, A., et al.[2021]

PSMA-targeted PET/CT imaging has shown superior detection rates for prostate cancer compared to older imaging methods, making it valuable for initial staging and restaging during biochemical recurrence.

Radioligand therapy (RLT) using Lutetium-177 (177Lu) linked to PSMA antibodies has been associated with improved overall survival rates in patients with metastatic castration-resistant prostate cancer, indicating its efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting PSMA Revolutionizes the Role of Nuclear Medicine in Diagnosis and Treatment of Prostate Cancer. Luining, WI., Cysouw, MCF., Meijer, D., et al.[2022]

Prostate-specific membrane antigen (PSMA) is a promising target for developing radiopharmaceuticals in treating aggressive prostate cancers, with ongoing clinical trials focusing on PSMA-targeted therapies, particularly using the β-particle-emitting radioisotope 177Lu.

PSMA PET imaging is crucial for evaluating tumor PSMA expression, helping to select the right patients for PSMA-targeted therapies, and studies are exploring PET parameters as predictive and prognostic biomarkers for treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of PET to Appropriately Select Patients for PSMA-Targeted Theranostics. Eshghi, A., Covington, MF., Eshghi, N., et al.[2023]

The study successfully converted a gallium-68 imaging agent into a lutetium-177 therapeutic agent for prostate cancer, demonstrating strong PSMA binding affinity comparable to the FDA-approved [177Lu]Lu-PSMA-617.

Biodistribution studies in mice showed that the new agent [177Lu]Lu-7 had a longer blood half-life and higher tumor uptake than both [177Lu]Lu-4 and [177Lu]Lu-PSMA-617, indicating its potential for improved therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177). Zha, Z., Choi, SR., Li, L., et al.[2022]

Lutetium-177 PSMA-617 (Lu-177-PSMA-617) has been approved by the FDA for treating patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have already undergone other treatments, indicating its efficacy in a specific patient population.

The paper outlines essential logistical and safety considerations for implementing a radiopharmaceutical therapy program, emphasizing the importance of developing proper operating procedures for administering Lu-177-PSMA-617 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Logistical, technical, and radiation safety aspects of establishing a radiopharmaceutical therapy program: A case in Lutetium-177 prostate-specific membrane antigen (PSMA) therapy. Zoberi, JE., Garcia-Ramirez, J., Luechtefeld, D., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11816243/

Unveiling Prostate-Specific Membrane Antigen's Potential ... This study explores the potential of a protein called prostate-specific membrane antigen (PSMA), which is widely used in prostate cancer (PCa) imaging and ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.1025

Prostate-specific membrane antigen (PSMA) expression in ... The PRISMA study aims to assess PSMA expression in pts with metastatic TNBC (mTNBC) via positron-emission tomography/computed tomography (PET/CT)

3. jnm.snmjournals.org jnm.snmjournals.org/content/65/11/1740

Efficacy and Toxicity of [ 177 Lu]Lu-PSMA-617 for Metastatic ... The phase 3 VISION trial demonstrated that 177 Lu-Lu-PSMA-617 prolonged overall survival (OS) and radiographic progression-free survival in patients with PSMA- ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10854516/

Head-to-Head Comparison of [18F]PSMA-1007 and [18F]FDG ... The study involves 10 TNBC patients, revealing comparable uptake of [ 18 F]PSMA-1007 and [ 18 F]FDG in primary and metastatic lesions.

5. sciencedirect.com sciencedirect.com/science/article/pii/S022352342500594X

PSMA targeted Therapy: From molecular mechanisms to ... Content: In a Phase III trial, 177Lu-PSMA-617 improved median overall survival (OS) from 11.3 to 15.3 months in metastatic castration-resistant prostate ...

6. mdpi.com mdpi.com/2072-6694/17/3/456

Unveiling Prostate-Specific Membrane Antigen's Potential ... High PSMA expression on PET/CT imaging helps identify patients eligible for treatment with PSMA-based radiopharmaceuticals labeled with beta- and alpha-emitting ...

7. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00451-5/fulltext

Single-dose 177Lu-PSMA-617 followed by maintenance ... A single priming dose of 177Lu-PSMA-617 followed by pembrolizumab maintenance was safe and had encouraging preliminary activity in patients with metastatic ...