[177Lu]Lu-NeoB + Capecitabine for Metastatic Breast Cancer

(NeoB-Cap1 Trial)

Recruiting at 36 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Novartis Pharmaceuticals

Must not be taking: Brivudine, NEP inhibitors

Disqualifiers: Visceral disease, Inflammatory breast cancer, others

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

Compensation: Varies

Number of Visits: 4

Duration: Up to 18 months

58 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with a specific type of metastatic breast cancer that has worsened despite previous treatments. The study aims to determine the optimal dose and schedule of the experimental drug [177Lu]Lu-NeoB (a radiopharmaceutical therapy) when combined with capecitabine. It evaluates how effectively these drugs work together against the cancer. Individuals with estrogen receptor-positive, HER2-negative metastatic breast cancer that has progressed after certain therapies might be suitable candidates. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new therapy.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants currently receiving brivudine or NEP inhibitors must discontinue these medications before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of [177Lu]Lu-NeoB and capecitabine is generally easy for patients to handle. Studies have found these treatments together to be safe, with most trial participants not experiencing serious side effects. The National Cancer Institute tracks side effects using a specific system, and results from these studies have been positive regarding safety.

Capecitabine, one of the drugs in this combination, has FDA approval for other cancer treatments, indicating its general safety when used correctly. Overall, while some side effects can occur, existing research suggests this treatment combination is safe for most patients in trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about [177Lu]Lu-NeoB combined with capecitabine for metastatic breast cancer because it offers a novel approach compared to traditional chemotherapy and hormone therapies. Unlike standard treatments that often target all rapidly dividing cells, [177Lu]Lu-NeoB is a targeted radioligand therapy. This treatment uses a radioactive component, lutetium-177, to specifically deliver radiation to cancer cells, potentially sparing healthy tissue. Additionally, the combination with capecitabine, a chemotherapy drug that is taken orally, may enhance the treatment's effectiveness while providing a more convenient administration method. This precision and convenience could lead to improved outcomes and quality of life for patients.

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

This trial will evaluate different dosages of the combination of [177Lu]Lu-NeoB and capecitabine for treating metastatic breast cancer. Studies have shown that this combination can help treat certain aggressive types of breast cancer. Previous trials demonstrated that [177Lu]Lu-NeoB is safe and tolerable for patients. It delivers radiation directly to cancer cells, while capecitabine, a chemotherapy drug, stops the cancer cells from growing. Early results are promising and suggest that this combination may slow tumor growth. However, more research is needed to confirm these effects in larger groups. ^{1 4 5 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults with a specific type of advanced breast cancer that's positive for certain receptors (GRPR+, ER+), negative for HER2, and has worsened after previous hormone therapy and CDK4/6 inhibitors. Participants must have measurable disease progression, may have received Enhertu® if HER2-low or PARP inhibitor therapy if they carry BRCA mutations.

Inclusion Criteria

I have signed the consent form to participate in the study.

I have at least one tumor that can be measured by medical imaging.

I have HER2-low breast cancer and may have been treated with Enhertu®.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

1 visit (in-person) for PET/CT or PET/MRI imaging

Treatment

Participants receive [177Lu]Lu-NeoB in combination with capecitabine. Treatment cycles are every 3 or 6 weeks depending on the dose regimen.

Up to 18 months

Site visits approximately every 3 weeks for the first 9 months, then every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment discontinuation, with a focus on long-term safety and survival.

5 years

Regular follow-up visits as per the Schedule of Assessments

What Are the Treatments Tested in This Trial?

Interventions

• [177Lu]Lu-NeoB

Trial Overview [177Lu]Lu-NeoB combined with Capecitabine is being tested to find the best doses and schedules in patients with metastatic breast cancer. The study has two parts: Phase I to determine safe dosage levels, and Phase II to test the effectiveness of these dosages on tumor growth.

How Is the Trial Designed?

Group I: Dose D: [177Lu]Lu-NeoB 100mCi q6w + capecitabine Experimental Treatment 3 Interventions

\[177Lu\]Lu-NeoB 100mCi q6w + Capecitabine 1000mg/m2 BID Day1-14 in a 21-day schedule

Group II: Dose C: [177Lu]Lu-NeoB 200mCi q6w + capecitabine Experimental Treatment 3 Interventions

\[177Lu\]Lu-NeoB 200mCi q6w + Capecitabine 1000mg/m2 BID Day1-14 in a 21-day schedule

Group III: Dose B: [177Lu]Lu-NeoB 100mCi q3w + capecitabine Experimental Treatment 3 Interventions

\[177Lu\]Lu-NeoB 100mCi q3w+ Capecitabine 1000mg/m2 BID Day1-14 in a 21-day schedule

Group IV: Dose A: [177Lu]Lu-NeoB 150mCi q6w + capecitabine Experimental Treatment 3 Interventions

\[177Lu\]Lu-NeoB 150mCi q6w + Capecitabine 1000mg/ m2 BID Day1-14 in a 21-day schedule

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

Lutetium-177 is a key radioisotope used in treating various cancers and other disorders, with advancements in its production and application over the last decade, particularly through direct neutron activation in research reactors.

The review highlights the development of stable 177Lu-based radiopharmaceuticals, emphasizing their clinical utility and potential benefits for cancer patients, especially in developing countries with limited access to advanced medical facilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of advances in the last decade on targeted cancer therapy using 177Lu: focusing on 177Lu produced by the direct neutron activation route. Chakravarty, R., Chakraborty, S.[2023]

Lutetium-177 coupled with a ligand for Prostate Specific Membrane Antigen ([177Lu]Lu-PSMA) is an innovative treatment for patients with advanced prostate cancer who have limited options after hormonal therapy and chemotherapy, requiring specific eligibility criteria including good health and adequate targeting of metastases.

The treatment involves four to six intravenous doses administered six weeks apart, with mild side effects such as dry mouth, fatigue, and bone marrow depression, and is currently available in select hospitals in the Netherlands, with broader access expected following EMA registration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lutetium-177-PSMA in metastasized prostate carcinoma]. van Golen, LW., Vogel, W., Lam, MGEH.[2023]

Lutetium-177 coupled with a ligand for Prostate Specific Membrane Antigen ([177Lu]Lu-PSMA) is an innovative treatment for patients with advanced prostate cancer who have limited options after hormonal therapy and chemotherapy, requiring specific eligibility criteria including good health and adequate targeting of metastases.

The treatment involves four to six intravenous doses administered six weeks apart, with mild side effects such as dry mouth, fatigue, and bone marrow depression, and is currently available in select hospitals in the Netherlands, with broader access expected following EMA registration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lutetium-177-PSMA in metastasized prostate carcinoma]. van Golen, LW., Vogel, W., Lam, MGEH.[2023]

Peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) has become a promising treatment option for neuroendocrine tumors and prostate cancer, with Lutathera® and Pluvicto® being key approved therapies.

The review emphasizes the need for comprehensive safety data and optimized procedures for using 177Lu radiopharmaceuticals, aiming to improve the risk-benefit balance in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals. Ladrière, T., Faudemer, J., Levigoureux, E., et al.[2023]

The UpFrontPSMA trial is evaluating the effectiveness and safety of combining lutetium-177 (177 Lu)-PSMA-617 with docetaxel in 140 men with newly diagnosed metastatic hormone-naïve prostate cancer, aiming to determine the proportion of patients achieving undetectable PSA levels after 12 months.

This study is significant as it compares the experimental treatment to standard docetaxel therapy while all patients receive continuous androgen deprivation therapy, potentially providing insights into improved treatment strategies for this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UpFrontPSMA: a randomized phase 2 study of sequential 177 Lu-PSMA-617 and docetaxel vs docetaxel in metastatic hormone-naïve prostate cancer (clinical trial protocol). Dhiantravan, N., Emmett, L., Joshua, AM., et al.[2021]

The novel radiopharmaceutical agent 177Lu-DOTA-DG was successfully synthesized with a high radiochemical yield and demonstrated excellent stability in human serum for up to 120 hours, indicating its potential for safe use in cancer imaging and therapy.

In preclinical studies, 177Lu-DOTA-DG caused significantly more DNA damage in cancer cells compared to untreated cells, suggesting its efficacy as a targeted treatment for cancer tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo and in vitro evaluation of 177Lu-labeled DOTA-2-deoxy-D-glucose in mice. A novel radiopharmaceutical agent for cells imaging and therapy. Zhang, J., Wang, Z., Liu, H., et al.[2019]

In a study of 47 patients with progressive well-differentiated neuroendocrine tumors (NETs) treated with 177Lu-Dotatate, the median progression-free survival was 34.1 months, indicating the treatment's efficacy in managing these tumors over time.

Factors such as having 5 or more bone metastases, non-gastroenteropancreatic NETs, high levels of chromogranin A, and pre-existing ascites were identified as significant predictors of poorer overall survival, helping to identify patients who may benefit less from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival predictors of 177Lu-Dotatate peptide receptor radionuclide therapy (PRRT) in patients with progressive well-differentiated neuroendocrine tumors (NETS). Swiha, MM., Sutherland, DEK., Sistani, G., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06247995?utm_source=trialradar

Study Details | NCT06247995 | A Phase I/II, Dose Finding ... Data show that [177Lu]Lu-NeoB has shown a good tolerability and safety ... [177Lu]Lu-NeoB and capecitabine. The National Cancer Institute (NCI) CTCAE ...

2. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/lutetium-lu-177-neob?pn=1

Clinical Trials Using Lutetium Lu 177-NeoB - NCI A Phase I/II, Dose Finding and Optimization Study of [177Lu]Lu-NeoB in Combination With Capecitabine in Patients With GRPR+, ER+, HER2- Metastatic Breast Cancer ...

3. isrctn.com isrctn.com/ISRCTN15516131

A Phase I/II, open-label, multi-center trial of [177Lu]Lu- ... The purpose of this study is to find the dose of a new drug called [177Lu]Lu-NeoB (Lutetium NeoB), when given together with the breast cancer ...

4. clinicaltrials.eu clinicaltrials.eu/inn/neob/

NEOB: A Promising New Drug for Cancer Treatment The trials are evaluating NeoB as both an imaging agent ([68Ga]Ga-NeoB) and a therapeutic agent ([177Lu]Lu-NeoB) to detect and treat GRPR-positive tumors. These ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20580328

Clinical Trials The purpose of this study is to determine the recommended doses (RD) and dosing regimens of [ 177Lu]Lu-NeoB in combination with capecitabine in adult patients ...

6. novartis.com novartis.com/clinicaltrials/study/nct06247995

Metastatic Breast Cancer After Progression on Previous ... Participant has metastatic breast cancer with radiologically confirmed progression of disease after the most recent therapy 7. Participant ...

7. clinicaltrials.eu clinicaltrials.eu/inn/lutetium-177lu-neobomb1/

Lutetium (177Lu)-Neobomb1 – Application in Therapy and ... Two significant clinical trials are currently underway to evaluate the safety and efficacy of LUTETIUM (177LU)-NEOBOMB1: A Phase I/II trial combining [177Lu]- ...