Atezolizumab + Chemotherapy for Neuroendocrine Carcinoma
Palo Alto (17 mi)Overseen byDavid B Zhen
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: National Cancer Institute (NCI)
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
What safety data is available for Atezolizumab and chemotherapy in treating neuroendocrine carcinoma?The provided research does not directly address the safety data for Atezolizumab (Tecentriq) combined with chemotherapy agents like Carboplatin, Cisplatin, and Etoposide in treating neuroendocrine carcinoma. The studies focus on managing chemotherapy-induced nausea and vomiting, particularly with antiemetic regimens like NEPA and Alizapride, but do not provide specific safety data for the combination treatment in question.13456
Is the drug combination Atezolizumab, Carboplatin, Cisplatin, and Etoposide promising for treating neuroendocrine carcinoma?Yes, the drug combination shows promise for treating neuroendocrine carcinoma. Atezolizumab, an immune checkpoint inhibitor, has shown promising results in clinical trials, especially when combined with other treatments like chemotherapy. This combination could expand treatment options and improve outcomes for patients with neuroendocrine carcinoma.2791112
What data supports the idea that Atezolizumab + Chemotherapy for Neuroendocrine Carcinoma is an effective treatment?The available research shows that immune checkpoint inhibitors, like Atezolizumab, have shown promising results when used in combination with chemotherapy for treating neuroendocrine neoplasms. Although no specific data on Atezolizumab combined with chemotherapy for neuroendocrine carcinoma is provided, the combination of immune therapies with chemotherapy has been noted to be more effective than using them alone. This suggests that Atezolizumab, when combined with chemotherapy, could potentially improve treatment outcomes for neuroendocrine carcinoma.2891011
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop all current medications. However, you must stop taking denosumab before joining the trial and replace it with a bisphosphonate. Also, if you are on active systemic therapy for another cancer, you may need to adjust or stop certain treatments, like glucocorticoid-containing regimens. It's best to discuss your specific medications with the trial team.
Eligibility Criteria
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.Inclusion Criteria
My cancer can be seen and measured on scans according to specific criteria.
I am 18 years old or older.
I can take care of myself but might not be able to do heavy physical work.
My cancer is a type of neuroendocrine carcinoma that cannot be surgically removed or cured with current treatments.
I will stop taking denosumab and switch to a bisphosphonate for the study.
I have brain lesions and haven't received any treatment for them.
Exclusion Criteria
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.
I do not have symptoms from cancer spread to my brain.
I do not have cancer spread to the lining of my brain and spinal cord.
Treatment Details
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.
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.
Atezolizumab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Tecentriq for:
- Melanoma
- Hepatocellular carcinoma
- Small cell lung cancer
- Non-small cell lung cancer
- Urothelial carcinoma
🇪🇺 Approved in European Union as Tecentriq for:
- Melanoma
- Hepatocellular carcinoma
- Small cell lung cancer
- Non-small cell lung cancer
- Urothelial carcinoma
Find a clinic near you
Research locations nearbySelect from list below to view details:
Bronson Battle CreekBattle Creek, MI
Corewell Health Grand Rapids Hospitals - Butterworth HospitalGrand Rapids, MI
Bronson Methodist HospitalKalamazoo, MI
West Michigan Cancer CenterKalamazoo, MI
More Trial Locations
Loading ...
Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
[Alizapride in the treatment of vomiting induced by cytostatic agents]. [2012]Most antineoplastic agents, particularly cisplatinum, cause nausea and vomiting. In an open study, 30 subjects receiving anticancer drugs were given the antiemetic Alizapride. The incidence of severe nausea was reduced from 50% to 24% on day 3. The percentage of patients without vomiting was raised to 77% until day 5. These results are in line with those of other clinical studies on Alizapride.
Phase II trial of paclitaxel, carboplatin, and etoposide in advanced poorly differentiated neuroendocrine carcinoma: a Minnie Pearl Cancer Research Network Study. [2015]To evaluate the efficacy of chemotherapy with paclitaxel, carboplatin, and etoposide in advanced adult poorly differentiated neuroendocrine carcinomas.
A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy. [2023]Safe, effective and convenient antiemetic regimens that preserve benefit over repeated cycles are needed for optimal supportive care during cancer treatment. NEPA, an oral fixed-dose combination of netupitant, a highly selective NK1 receptor antagonist (RA), and palonosetron (PALO), a distinct 5-HT3 RA, was shown to be superior to PALO in preventing chemotherapy-induced nausea and vomiting after a single cycle of highly (HEC) or moderately (MEC) emetogenic chemotherapy in recent trials. This study was designed primarily to assess the safety but also to evaluate the efficacy of NEPA over multiple cycles of HEC and MEC.
Review of oral fixed-dose combination netupitant and palonosetron (NEPA) for the treatment of chemotherapy-induced nausea and vomiting. [2018]Current guidelines recommend the combination of a neurokinin-1 (NK1) receptor antagonist (RA) and a 5-hydroxytryptamine-3 (5-HT3) RA, together with corticosteroids, in order to prevent chemotherapy-induced nausea and vomiting with anthracycline-cyclophosphamide and highly emetogenic chemotherapy, and it is to be considered with moderately emetogenic chemotherapy. Netupitant and palonosetron (NEPA) is a fixed-dose combination of netupitant, a novel, highly selective NK1 RA, and palonosetron, a new-generation 5-HT3 RA, targeting two major emetic pathways in a single oral capsule. In clinical trials, NEPA administered on day 1 together with dexamethasone was highly effective and well tolerated in the prevention of chemotherapy-induced nausea and vomiting in patients with solid tumors undergoing moderately emetogenic chemotherapy or highly emetogenic chemotherapy. NEPA offers maximal convenience, and as a simple guideline-based regimen, has the potential to improve adherence to guidelines.
Prevention of Nausea and Vomiting in Patients Undergoing Oral Anticancer Therapies for Solid Tumors. [2018]Chemotherapy-induced nausea and vomiting (CINV) is still a common and debilitating side effect despite recent advances in its prevention and treatment. The intrinsic emetogenicity of chemotherapy agents allowed grouping into four risk groups (high, moderate, low, and minimal risk of emetogenicity). The prevention of acute and delayed CINV for intravenous agents and one day regimens is well studied, although, there are few data about management of CINV induced by oral cytotoxic agents and targeted therapies, usually administered in extended regimens of daily oral use. Until now treatment of nausea and vomiting caused by oral antineoplastic agents remains largely empirical. The level of evidence of prophylactic antiemetics recommended for these agents is low. There are differences in the classification of emetogenic potential of oral antineoplastic agents between the international guidelines and different recommendations for prophylactic antiemetic regimens. Herein we review the evidence for antiemetic regimens for the most used oral antineoplastic agents for solid tumors and propose antiemetic regimens for high to moderate risk and low to minimal risk of emetogenicity.
Delayed nausea and vomiting from carboplatin doublet chemotherapy. [2018]Delayed nausea and vomiting following administration of carboplatin containing chemotherapy regimen remains a clinically significant problem for patients with cancer despite administration of standard antiemetic prophylaxis comprising of a 5-HT3 antagonist and dexamethasone. We performed a prospective study to define the incidence and risk factors for delayed chemotherapy-induced nausea and vomiting (CINV).
Pembrolizumab monotherapy in patients with previously treated metastatic high-grade neuroendocrine neoplasms: joint analysis of two prospective, non-randomised trials. [2021]Metastatic high-grade neuroendocrine neoplasms (G3NENs) have limited treatment options after progression on platinum-based therapy. We addressed the role of Pembrolizumab in patients with previously treated metastatic G3NENs.
Post first-line dacarbazine or temozolomide in neuroendocrine carcinoma. [2022]First-line chemotherapy in metastatic neuroendocrine carcinomas (NECs) is based on etoposide and platinum. However, there is no standard concerning second-line treatment. The objective of this study was to evaluate efficacy and tolerance of dacarbazine or temozolomide in metastatic digestive NEC as post first-line treatment.
Activity and Safety of Immune Checkpoint Inhibitors in Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis. [2021]Immune-checkpoint inhibitors (ICIs) have widened the therapeutic scenario of different cancer types. Phase I/II trials have been designed to evaluate the role of ICIs both as single agents and in combination in neuroendocrine neoplasms (NENs), but as yet no randomized controlled phase III trials have been carried out. A systematic review and meta-analysis of studies published could help to reduce the biases of single-phase II trials. Efficacy data were obtained on 636 patients. Pooled percentages of the overall response rate (ORR) and disease control rate (DCR) were 10% (95% CI: 6-15%, I2 = 67%, p < 0.1) and 42% (95% CI: 28-56%, I2 = 93%, p < 0.1), respectively. Median progression-free survival (mPFS) was 4.1 months (95% CI 2.6-5.4; I2 = 96%, p < 0.1) and median overall survival (mOS) was 11 months (95% CI 4.8-21.1; I2 = 98%, p < 0.1). Among the ICIs used as single agents, the anti-PD1 toripalimab achieved the highest ORR. Combination regimens were superior to monotherapy, e.g., the ICI combination nivolumab + ipilimumab, and the ICI + anti-angiogenetic combination atezolizumab + bevacizumab, both of which warrant further investigation. Promising efficacy and a good safety profile of ICIs represent a valid opportunity for expanding the therapeutic landscape of NENs. Predictive biomarkers are needed to identify the most suitable candidates for these regimens.
First-line treatment of camrelizumab combined with chemotherapy in advanced gastroenteropancreatic neuroendocrine carcinoma: Study protocol for a prospective, multicenter, phase II study. [2022]Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a group of rare but highly aggressive malignancies. The standard chemotherapy regimens composed of etoposide and cisplatin/carboplatin (EP/EC) are of limited efficacy. This prospective, multicenter, phase II study is conducted to explore the effectiveness and safety of first-line anti-PD-1 antibody (camrelizumab) combined with chemotherapy in advanced GEP-NEC patients.
Future therapeutic strategies in the treatment of extrapulmonary neuroendocrine carcinoma: a review. [2023]Neuroendocrine neoplasms (NENs) are rare malignancies arising most commonly in the gastrointestinal and bronchopulmonary systems. Neuroendocrine carcinomas (NECs) are a subgroup of NENs characterised by aggressive tumour biology, poor differentiation and dismal prognosis. Most NEC primary lesions arise in the pulmonary system. However, a small proportion arise outside of the lung and are termed extrapulmonary (EP)-, poorly differentiated (PD)-NECs. Patients with local or locoregional disease may benefit from surgical excision; however, this is often not an option, due to late presentation. To date, treatment has mirrored that of small-cell lung cancer, with platinum-etoposide forming the basis of first-line treatment. There is a lack of consensus in relation to the most effective second-line treatment option. Low incidence, an absence of representative preclinical models and a lack of understanding of the tumour microenvironment all present challenges to drug development in this disease group. However, progress made in elucidating the mutational landscape of EP-PD-NEC and the observations made in several clinical trials are paving the way towards improving outcomes for these patients. The optimisation and strategic delivery of chemotherapeutic interventions according to tumour characteristics and the utilisation of targeted and immune therapies in clinical studies have yielded mixed results. Targeted therapies that complement specific genetic aberrations are under investigation, including AURKA inhibitors in those with MYCN amplifications, BRAF inhibitors in those with BRAFV600E mutations and EGFR suppression, and Ataxia Telangiectasia and Rad3-related inhibitors in patients with ATM mutations. Immune checkpoint inhibitors (ICIs) have conferred promising results in several clinical trials, particularly with dual ICIs and in combination with targeted therapy or chemotherapy. However, further prospective investigations are required to elucidate the impact of programmed cell death ligand 1 expression, tumour mutational burden and microsatellite instability on response. This review aims to explore the most recent developments in the treatment of EP-PD-NEC and contribute towards the requirement for clinical guidance founded on prospective evidence.
Comparison of efficacy and safety between carboplatin-etoposide and cisplatin-etoposide combination therapy in patients with advanced neuroendocrine carcinoma, retrospective study. [2023]Neuroendocrine carcinoma (NEC) is characterized by a poor prognosis and is generally treated with platinum and etoposide combination therapy as first-line chemotherapy. However, it remains uncertain whether carboplatin and etoposide combination therapy (CE) and cisplatin and etoposide combination therapy (PE) have comparable treatment efficacy. In this retrospective analysis, we compared the efficacy and safety of CE and PE in patients with NEC.