What side effects are associated with this type of intervention?

The most common treatments for Neuroendocrine Carcinoma, particularly those involving Atezolizumab, include a combination of immunotherapy and chemotherapy. Atezolizumab, a monoclonal antibody, can cause side effects such as increased blood creatine phosphokinase, diarrhea, rash, hypertension, and dermatitis acneiform. Serious adverse events may include autoimmune conditions like uveitis, thyroid eye disease, and exacerbation of paraneoplastic syndromes. When combined with chemotherapy agents like cisplatin, carboplatin, and etoposide, additional side effects may include nausea, fatigue, and myelosuppression.

What prior FDA approvals exist?

The FDA has approved several immunotherapy drugs for the treatment of various cancers, including monoclonal antibodies like Atezolizumab. Atezolizumab itself has been approved for use in combination with chemotherapy for extensive-stage small cell lung cancer (ES-SCLC), which shares some treatment similarities with neuroendocrine carcinomas. Other related drugs include Pembrolizumab and Nivolumab, which are also monoclonal antibodies targeting PD-1/PD-L1 pathways and have shown efficacy in different types of cancers, including non-small cell lung cancer and renal cell carcinoma. These treatments work by enhancing the immune system's ability to attack cancer cells and inhibit tumor growth and spread.

What other types of research exist?

Promising alternatives to Atezolizumab for Neuroendocrine Carcinoma patients include other immune checkpoint inhibitors such as Pembrolizumab and Nivolumab, which target PD-1. Additionally, novel therapies like bispecific antibodies and chimeric-antigen-receptor (CAR) T cells are emerging as potential treatments. These therapies aim to enhance the immune system's ability to target and destroy cancer cells.

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Monoclonal Antibodies

Atezolizumab + Chemotherapy for Neuroendocrine Carcinoma

Phase 2 & 3

Recruiting

Led By David B Zhen

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants must have radiologically evaluable disease, measurable or non-measurable, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. All measurable and non-measurable lesions must be assessed by CT scan with IV contrast within 28 days prior to registration. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form

Participants must be >= 18 years of age

Must not have

Participants must not have specific medical conditions including uncontrolled hypercalcemia, immunodeficiency, autoimmune diseases, pulmonary conditions, cardiovascular disease, recent major surgical procedures, severe infections, active tuberculosis, prior transplants, recent live, attenuated vaccine administration, pregnancy, or lack of effective contraceptive use

Participants must not have symptomatic central nervous system (CNS) metastases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years from study enrollment

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new treatment combining an immune-boosting drug with standard chemotherapy for patients with a specific type of aggressive cancer that has spread. The goal is to help the immune system fight the cancer and use chemotherapy to kill cancer cells.

Who is the study for?

This trial is for adults with advanced or metastatic extrapulmonary neuroendocrine carcinoma that's not eligible for surgery. They must have a good performance status, no prior treatments for advanced NEC (except possibly one cycle of specific chemo), and meet certain lab test criteria. People with symptomatic brain metastases, active cancers elsewhere, severe allergies to trial drugs, or certain medical conditions can't join.

What is being tested?

The study compares standard chemotherapy (cisplatin/carboplatin and etoposide) alone versus adding the immunotherapy drug Atezolizumab to it in treating poorly differentiated neuroendocrine cancer outside the lung. It also looks at whether continuing Atezolizumab after initial treatment is beneficial.

What are the potential side effects?

Atezolizumab may cause immune-related reactions affecting organs, infusion reactions similar to allergic responses, fatigue, and increased risk of infections. Chemotherapy can lead to nausea, hair loss, blood cell count changes increasing infection risk or bleeding tendency.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer can be seen and measured on scans according to specific criteria.

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I am 18 years old or older.

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

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My cancer is a type of neuroendocrine carcinoma that cannot be surgically removed or cured with current treatments.

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I will stop taking denosumab and switch to a bisphosphonate for the study.

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I have brain lesions and haven't received any treatment for them.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have severe health issues like uncontrolled high calcium, immune problems, lung or heart diseases, recent surgeries, serious infections, TB, past organ transplants, recent vaccinations with live viruses, and I am not pregnant or failing to use effective birth control.

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I do not have symptoms from cancer spread to my brain.

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I do not have cancer spread to the lining of my brain and spinal cord.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years from study enrollment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years from study enrollment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years from study enrollment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall survival

Secondary study objectives

Clinical benefit rate (confirmed CR or PR of any amount of time or stable disease for 6 months or longer)

Duration of response

Objective response rate (confirmed complete response [CR] or partial response [PR])

+1 more

Side effects data

From 2012 Phase 3 trial • 256 Patients • NCT01005680

51%

Neutropenia

47%

Leukopenia

46%

Nausea

43%

Vomiting

35%

Anaemia

31%

Decreased appetite

26%

Haemoglobin decreased

26%

Fatigue

25%

Constipation

25%

White blood cell count decreased

24%

Neutrophil count decreased

19%

Alanine aminotransferase increased

13%

Platelet count decreased

12%

Rash

10%

Aspartate aminotransferase increased

10%

Thrombocytopenia

Blood sodium decreased

Hypokalaemia

Insomnia

Pyrexia

Hyponatraemia

Blood creatinine increased

Lymphopenia

Diarrhoea

Dyspepsia

Red blood cell count decreased

Cough

Dizziness

Bone marrow failure

Dyspnoea

Cerebral infarction

Ischaemic stroke

Pulmonary embolism

Embolism venous

Superior vena cava syndrome

100%

80%

60%

40%

20%

Study treatment Arm

Gemcitabine Plus Cisplatin (GC)

Pemetrexed Plus Cisplatin (PC)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Arm II (atezolizumab, platinum drug, etoposide, observation)Experimental Treatment8 Interventions

During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study.

Group II: Arm I (atezolizumab, platinum drug, etoposide)Experimental Treatment7 Interventions

During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. During maintenance phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study.

Group III: Arm III (platinum drug, etoposide, observation)Active Control7 Interventions

During induction phase, patients receive carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Carboplatin

2014

Completed Phase 3

~6120

Biospecimen Collection

2004

Completed Phase 3

~2020

Cisplatin

2013

Completed Phase 3

~3120

Computed Tomography

2017

Completed Phase 2

~2740

Etoposide

2010

Completed Phase 3

~2960

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Atezolizumab

2016

Completed Phase 3

~5860

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Neuroendocrine Carcinoma (NEC) include chemotherapy, targeted therapies, and immunotherapy. Chemotherapy agents like cisplatin and etoposide work by killing rapidly dividing cancer cells or inhibiting their growth. Targeted therapies, such as somatostatin analogs (e.g., lanreotide), inhibit hormone secretion and tumor growth. Immunotherapy, including monoclonal antibodies like Atezolizumab, enhances the immune system's ability to attack cancer cells and disrupts tumor cell growth and spread. These mechanisms are crucial for NEC patients as they offer multiple avenues to control tumor progression, improve survival rates, and potentially reduce side effects compared to traditional chemotherapy alone.

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