Molecularly Targeted Therapy for Advanced Cancer

Overseen By Julie L Sutcliffe, Phd

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Davis

Must not be taking: Warfarin

Disqualifiers: Congestive heart failure, Active infection, others

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

Compensation: Varies

Number of Visits: 5

Duration: 1 day

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new treatment approach for individuals with advanced cancers that have metastasized. It employs a pair of targeted drugs, [68Ga]Ga DOTA-5G (for imaging) and [177Lu]Lu DOTA-ABM-5G (for therapy), to evaluate their ability to identify and treat cancer cells. The trial seeks participants with specific types of cancer, including those affecting the stomach, intestines, and breast, who have not responded to other treatments. Candidates dealing with these cancers that have spread and progressed despite treatment may be suitable for this study. 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 new treatment.

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

The trial requires that you stop any prior systemic therapy at least 2 weeks before the PET scan. This is known as a washout period, which means you need to be off those medications for a certain time before starting the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that a pair of treatments, [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G, is being tested for safety in humans. Earlier studies found these treatments might be safe and tolerable for patients with metastatic cancer.

The treatment [177Lu]Lu DOTA-ABM-5G, in particular, has shown potential in diagnosing and treating certain cancers, such as prostate and stomach cancer, suggesting it might be well-tolerated. However, since this treatment remains in the early testing stages, researchers are still gathering safety information. Participants should know that while initial results are promising, the treatment is still under evaluation for safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard chemotherapy and radiation treatments for advanced cancer, [177Lu]Lu DOTA-ABM-5G is a targeted radionuclide therapy. Researchers are excited about this treatment because it uses a radioactive compound that specifically targets cancer cells, potentially minimizing damage to healthy tissue. This precision targeting is achieved through a compound that binds to cancer cells, allowing the radioactive element to destroy them from within. By focusing directly on the cancerous cells, this treatment could offer a more effective and less harmful approach than conventional therapies.

What evidence suggests that this treatment might be an effective treatment for metastatic cancer?

Research shows that [177Lu]Lu DOTA-ABM-5G, which participants in this trial may receive, could be promising for treating some advanced cancers. Studies have found that lutetium-177, the active ingredient, can help diagnose and treat cancers like prostate and stomach cancer. In this trial, [68Ga]Ga DOTA-5G is used for imaging to confirm eligibility for the [177Lu]Lu DOTA-ABM-5G therapy, helping to identify cancer spread and deliver targeted radiation therapy. Early results suggest it might also work for pancreatic cancer. Although limited data from human studies exist, this targeted approach aims to attack cancer cells more precisely, potentially improving treatment results. ^{2 3 5 6 7}

Who Is on the Research Team?

Julie Sutcliffe

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for patients with metastatic cancer. Specific eligibility criteria are not provided, but typically participants would need to be in good health aside from their cancer and have a life expectancy that allows them to complete the study.

Inclusion Criteria

My scans show at least one cancer spot that stands out clearly.

My cancer has worsened after treatment as shown by scans.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I am on warfarin for blood thinning.

I have not had treatment for another cancer, except skin or early breast/cervical cancer, in the last 2 years.

I have severe heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Imaging

Participants undergo [68Ga]Ga DOTA-5G PET/CT scans to confirm eligibility for the [177Lu]Lu DOTA-ABM-5G therapy

2 hours

1 visit (in-person)

Treatment

Participants receive a single dose of [177Lu]Lu DOTA-ABM-5G therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 days

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G

Trial Overview The study is testing [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G theranostics pair. It's a Phase I trial, which means it's the first time these treatments are being tested in humans to check safety and how well they work.

How Is the Trial Designed?

Group I: [177Lu]Lu DOTA-ABM-5G single dose therapy study Experimental Treatment 1 Intervention

Patients will be undergo \[68Ga\]Ga DOTA-5G PET/CT scans to confirm eligibility for the \[177Lu\]Lu DOTA-ABM-5G therapy. Patients with sufficient lesion uptake of \[68Ga\]Ga DOTA-5G PET/CT will be offered therapy.

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

The novel radiopharmaceutical 177Lu-DOTA-PSMA-GUL targets prostate cancer cells by binding to the prostate-specific membrane antigen (PSMA) and shows promising pharmacokinetics, with an average elimination half-life of 0.30 to 0.33 hours in rats.

Tissue distribution studies revealed that 177Lu-DOTA-PSMA-GUL is primarily eliminated through the kidneys, with significant accumulation in the prostate, indicating its potential effectiveness as a targeted therapy for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of pharmacokinetics and tissue distribution of a novel lutetium-labeled PSMA-targeted ligand, 177Lu-DOTA-PSMA-GUL, in rats by using LC-MS/MS. Song, CH., Kim, K., Kang, E., et al.[2022]

The newly developed PSMA-targeting ligands [(68)Ga/(177)Lu]DOTAGA-ffk(Sub-KuE] show high affinity and specific internalization in prostate cancer cells, indicating their potential for effective diagnostic imaging and therapy.

These ligands demonstrated favorable pharmacokinetics, including low non-specific uptake and high tumor accumulation in LNCaP-tumor-bearing mice, suggesting they could be highly effective in managing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and preclinical evaluation of DOTAGA-conjugated PSMA ligands for functional imaging and endoradiotherapy of prostate cancer. Weineisen, M., Simecek, J., Schottelius, M., et al.[2022]

177Lu-DOTA-Peptide 2, a new radioantagonist, showed high stability and selective binding to somatostatin receptors in HT-29 colorectal cancer cells, indicating its potential for targeted therapy.

The study demonstrated that 177Lu-DOTA-Peptide 2 has a low internalization rate and a high tumor uptake, making it a promising candidate for radionuclide therapy in treating somatostatin receptor-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells. Behnammanesh, H., Erfani, M., Hajiramezanali, M., et al.[2023]

The newly developed 177Lu-scFvD2B radiopharmaceutical shows improved pharmacokinetic properties, with high stability and yield, and demonstrates better binding and internalization in PSMA-positive prostate cancer cells compared to negative controls.

In vivo studies in mice indicate that 177Lu-scFvD2B has a favorable biokinetic profile, with rapid clearance from non-target tissues and sustained uptake in tumors, suggesting its potential for effective radiation therapy in advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen. Carpanese, D., Ferro-Flores, G., Ocampo-Garcia, B., et al.[2021]

In a phase II trial involving men with metastatic, castration-resistant prostate cancer, Lutetium-177 PSMA-617 was shown to extend survival and enhance quality of life for patients whose disease progressed despite standard treatments.

This study highlights the potential of targeted radionuclide therapy as an effective option for patients with advanced prostate cancer, suggesting a promising new avenue for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radionuclide Treatment Yields Responses in mCRPC. [2020]

The maximum tolerated dose (MTD) of (177)Lu-J591 for treating androgen-independent prostate cancer was determined to be 70 mCi/m², with multiple doses of 30 mCi/m² being well tolerated by patients.

The treatment showed promising biological activity, with 4 patients experiencing significant declines in prostate-specific antigen (PSA) levels and 46% of patients achieving PSA stabilization, indicating potential effectiveness in targeting prostate cancer metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of 177lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer. Bander, NH., Milowsky, MI., Nanus, DM., et al.[2022]

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]

The novel chelator picaga, when used in the 177Lu-picaga-Alb53-PSMA construct, demonstrated significant tumor regression and increased median survival (54 days) in prostate-specific membrane antigen (PSMA)-expressing tumor xenografts compared to other treatments.

In a comparative study, 177Lu-picaga-Alb53-PSMA outperformed both the vehicle and other radiotherapeutics, indicating its potential as a more effective option for targeted radiotherapy in cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of 177Lu and 47Sc Picaga-Linked, Prostate-Specific Membrane Antigen-Targeting Constructs for Their Radiotherapeutic Efficacy and Dosimetry. Vaughn, BA., Loveless, CS., Cingoranelli, SJ., et al.[2022]

The study successfully developed two new PSMA-targeting agents, (R)-[68Ga/177Lu]-DOTAGA and (S)-[68Ga/177Lu]-DOTAGA, which can be used for both imaging and therapy in prostate cancer, showing high binding affinity to PSMA.

While both isomers demonstrated similar biological behavior in terms of cell uptake and biodistribution in tumor-bearing mice, the (S)-isomer formed complexes with Lu more quickly, which could be important for future radionuclide therapy development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and Evaluation of 68Ga- and 177Lu-Labeled (R)- vs (S)-DOTAGA Prostate-Specific Membrane Antigen-Targeting Derivatives. Zhao, R., Ploessl, K., Zha, Z., et al.[2021]

The targeted alpha-particle therapy [225Ac]Ac-DOTA-TATE showed promising efficacy in delaying tumor growth in small animal models of lung neuroendocrine neoplasms, indicating its potential for treating patients who are resistant to standard therapies like [177Lu]Lu-DOTA-TATE.

In toxicity studies, [225Ac]Ac-DOTA-TATE demonstrated a high safety profile with no significant adverse effects in most animals, although higher doses led to chronic nephropathy, highlighting the need for careful dosing in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of [225Ac]Ac-DOTA-TATE for treatment of lung neuroendocrine neoplasms. Tafreshi, NK., Pandya, DN., Tichacek, CJ., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04665947

NCT04665947 | First-in-human Study of the Theranostic ... This is a Phase I, first-in-human study to evaluate the safety and efficacy of the [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G theranostic pair in patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11002837/

Current clinical application of lutetium‑177 in solid tumors ... As a result, 177Lu can be used for both diagnosis and treatment for diseases such as prostatic and gastric cancer. Therefore, based on the available data, the ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-13843

Gallium Ga 68-DOTA-5G and Lutetium Lu 177-DOTA-ABM ... Gallium Ga 68-DOTA-5G and lutetium Lu 177-DOTA-ABM-5G may be an effective combination for diagnosing and treating patients with pancreatic cancer. Eligibility ...

4. withpower.com withpower.com/trial/phase-1-neoplasm-metastasis-3-2024-49a96

Molecularly Targeted Therapy for Advanced Cancer This is a Phase I study to evaluate the safety and efficacy of the \[68Ga\]Ga DOTA-5G and \[177Lu\]Lu DOTA-ABM-5G theranostics pair in patients with metastatic ...

5. mycancergenome.org mycancergenome.org/content/drugs/[177Lu]Lu%20DOTA-ABM-5G/

[177lu]lu dota-abm-5g [177lu]lu dota-abm-5g has been investigated in 1 clinical trial, of which 1 is open and 0 are closed. Of the trial investigating [177lu]lu dota-abm-5g, 1 is ...

6. jnm.snmjournals.org jnm.snmjournals.org/content/64/supplement_1/p1300

First-in-human study of the theranostic pair [68Ga]Ga DOTA ... This is a Phase I, first-in-human study to evaluate the safety of the radiotheranostic peptide pair, [ 68 Ga]Ga DOTA-5G and [ 177 Lu]Lu DOTA-ABM-5G in patients ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-03571

A Theranostic Approach ([68Ga]Ga DOTA-5G and [177Lu] ... A theranostic approach with [68Ga]Ga DOTA-5G and [177]Lu DOTA-ABM-5G may be safe, tolerable and/or effective in detecting and treating metastatic cancer.