BI 764532 + Chemotherapy for Neuroendocrine Tumors

Recruiting at 25 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must be taking: Platinum-based chemotherapy

Disqualifiers: Merkel cell carcinoma, Medullary thyroid carcinoma, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 months

55 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is open to adults aged 18 and older or above legal age who have a specific type of advanced neuroendocrine cancer (NEC). Their tumours must be positive for a marker called DLL3. The purpose of this study is to test a medicine called BI 764532 in addition to chemotherapy. The study has 2 parts. Part A of this study aims to find out the highest dose of BI 764532 that people can tolerate in addition to chemotherapy. The purpose of Part B is to find out how well people can tolerate BI 764532 in combination with different chemotherapies. Researchers also want to find out whether BI 764532 in combination with chemotherapy helps people with NEC. Participants get different doses of BI 764532 as an infusion into a vein. In addition, they get platinum-based chemotherapy as infusions into a vein. Participants can continue treatment up to 3 years if they benefit from treatment and can tolerate it. Participants visit their doctors regularly. During these visits, the doctors collect information about participants' health and take note of any unwanted effects. Doctors also regularly check the size of the tumour.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should not need steroids or anti-convulsants for at least 7 days before starting the trial medication.

How is the drug BI 764532 different from other treatments for neuroendocrine tumors?

BI 764532 is unique because it is being studied in combination with chemotherapy for neuroendocrine tumors, which are typically resistant to many standard chemotherapy treatments. This approach may offer a new option for patients with these rare and challenging tumors. ^{1 2 3 4 5}

Eligibility Criteria

Adults with advanced neuroendocrine cancer (NEC) that tests positive for DLL3 can join. They must have a measurable tumor, expect to live at least 12 weeks, and not have had certain radiotherapies recently. The trial is open to those over 18 or the legal age in their country who can consent.

Inclusion Criteria

I have signed the consent form for this trial.

Minimum life expectancy of 12 weeks

I am fully active or can carry out light work.

Exclusion Criteria

I have not had extensive radiotherapy, including to the brain, within the last week.

My cancer has spread to the lining of my brain and spinal cord.

Previous treatment in this trial

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive different doses of BI 764532 in combination with platinum-based chemotherapy as infusions into a vein. Treatment can continue up to 3 years if beneficial and tolerated.

Up to 36 months

Regular visits for health monitoring and tumor size checks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• BI 764532

Trial Overview The study evaluates BI 764532 plus chemotherapy in two parts: finding the highest tolerable dose of BI 764532 (Part A), and assessing tolerance and effectiveness with different chemotherapies (Part B). Treatment involves infusions up to three years if beneficial.

Participant Groups

Group I: Part B: BI 764532 + cisplatin + etoposide Experimental Treatment 3 Interventions

Group II: Part B: BI 764532 + carboplatin + etoposide Experimental Treatment 3 Interventions

Group III: Part A: BI 764532 medium dose + carboplatin + etoposide Experimental Treatment 3 Interventions

Group IV: Part A: BI 764532 low dose + carboplatin + etoposide Experimental Treatment 3 Interventions

Group V: Part A: BI 764532 high dose + carboplatin + etoposide Experimental Treatment 3 Interventions

BI 764532 is already approved in United States for the following indications:

Approved in United States as BI 764532 for:

• None approved; under investigation for extensive-stage small cell lung cancer (ES-SCLC) and extrapulmonary neuroendocrine carcinoma (epNEC)

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

Intestinal neuroendocrine tumors (NETs) are diverse and vary in treatment based on their location, with small intestinal NETs typically treated first with somatostatin analogs, and options like everolimus or interferon alpha available if progression occurs.

Rectal NETs can be effectively treated with somatostatin analogs and peptide receptor radionuclide therapy (PRRT), while more aggressive colonic NETs often require everolimus or cytotoxic agents, highlighting the importance of tumor characteristics in determining treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical Therapy of Gastrointestinal Neuroendocrine Tumors. Öberg, K.[2020]

Bortezomib, a proteasome inhibitor, shows short-term sensitizing effects when combined with DNA-damaging therapies like cisplatin and radiation, by impairing DNA repair mechanisms in well-differentiated gastroenteropancreatic neuroendocrine neoplasms.

Despite these promising short-term effects, the study found no significant long-term therapeutic advantage of combining bortezomib with peptide receptor radionuclide therapy (PRRT) due to high tumor heterogeneity observed in the in vivo mouse model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does the proteasome inhibitor bortezomib sensitize to DNA-damaging therapy in gastroenteropancreatic neuroendocrine neoplasms? - A preclinical assessment in vitro and in vivo. Briest, F., Koziolek, EJ., Albrecht, J., et al.[2021]

In a noninterventional trial involving patients with advanced neuroendocrine tumors (NETs), the combination of Everolimus and Octreotide LAR demonstrated a clinical benefit rate of 69%, indicating significant efficacy in managing the disease.

The treatment was well-tolerated, with most patients experiencing stable disease, and a small number continuing therapy for over 12 cycles, suggesting a favorable safety profile in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everolimus plus octreotide long-acting repeatable in advanced neuroendocrine tumors in the routine tertiary cancer care setting: An Indian experience. Tippeswamy, R., Patil, S., Sateesh, CT., et al.[2016]

In a study of 78 patients with advanced neuroendocrine tumors (NETs), oxaliplatin-based chemotherapy demonstrated a disease control rate of 80%, with a median progression-free survival of 8 months and overall survival of 32 months, indicating its potential efficacy.

The treatment was generally well-tolerated, with manageable side effects primarily being neurological and gastrointestinal, suggesting that oxaliplatin-based regimens could be a viable option for patients with advanced NETs, particularly those with pancreatic tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors: Clinical Outcomes and Preliminary Correlation with Biological Factors. Spada, F., Antonuzzo, L., Marconcini, R., et al.[2018]

Chemotherapy for malignant neuroendocrine tumors, particularly those of pancreatic origin, can be effective, with up to 60% of patients responding positively to a combination of streptozocin and doxorubicin.

However, well-differentiated neuroendocrine tumors from the gastrointestinal tract show almost no response to chemotherapy, highlighting the need for tailored treatment approaches based on tumor type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine tumours of the gastrointestinal tract: Chemotherapy. Arnold, R., Rinke, A., Schmidt, Ch., et al.[2013]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Medical Therapy of Gastrointestinal Neuroendocrine Tumors. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Does the proteasome inhibitor bortezomib sensitize to DNA-damaging therapy in gastroenteropancreatic neuroendocrine neoplasms? - A preclinical assessment in vitro and in vivo. [2021]

3. India pubmed.ncbi.nlm.nih.gov

Everolimus plus octreotide long-acting repeatable in advanced neuroendocrine tumors in the routine tertiary cancer care setting: An Indian experience. [2016]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors: Clinical Outcomes and Preliminary Correlation with Biological Factors. [2018]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Endocrine tumours of the gastrointestinal tract: Chemotherapy. [2013]