Randomized Phase II/III Trial of First Line Platinum/Etoposide With or Without Atezolizumab (NSC#783608) in Patients With Poorly Differentiated Extrapulmonary Small Cell Neuroendocrine Carcinomas (NEC)

Plain English Summary

Evaluating the Addition of the Immunotherapy Drug Atezolizumab to Standard Chemotherapy Treatment for Advanced or Metastatic Neuroendocrine Carcinomas That Originate Outside the Lung is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Advanced Extrapulmonary Neuroendocrine Carcinoma, Metastatic Extrapulmonary Neuroendocrine Carcinoma, Recurrent Extrapulmonary Neuroendocrine Carcinoma, Unresectable Extrapulmonary Neuroendocrine Carcinoma. Tests the addition of the immunotherapy drug Atezolizumab to standard chemotherapy for advanced or metastatic neuroendocrine carcinomas outside the lung. For patients with poorly differentiated extrapulmonary neuroendocrine cancer, who have had previous platinum-based therapy and are not eligible for surgery or radiation. Participation involves IV infusions of Atezolizumab, cisplatin, or carboplatin, and etoposide, along with regular CT scans and blood samples. Alternative treatments include standard chemotherapy alone or other immunotherapy options. The trial aims to enroll 189 participants.

Official Summary

This phase II/III trial compares the effect of immunotherapy with atezolizumab in combination with standard chemotherapy with a platinum drug (cisplatin or carboplatin) and etoposide versus standard therapy alone for the treatment of poorly differentiated extrapulmonary (originated outside the lung) neuroendocrine cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). The other aim of this trial is to compare using atezolizumab just at the beginning of treatment versus continuing it beyond the initial treatment. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin and carboplatin are in a class of medications known as platinum-containing compounds that work by killing, stopping or slowing the growth of cancer cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. Giving atezolizumab in combination with a platinum drug (cisplatin or carboplatin) and etoposide may work better in treating patients with poorly differentiated extrapulmonary neuroendocrine cancer compared to standard therapy with a platinum drug (cisplatin or carboplatin) and etoposide alone.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if diagnosed with advanced or metastatic poorly differentiated extrapulmonary neuroendocrine cancer, not eligible for surgery or radiation. Not eligible if had prior treatment with immune checkpoint inhibitors or systemic immunostimulatory agents within the last 4 weeks. Age 18 or older, must be in good general health, and have measurable disease. Must not have symptomatic central nervous system metastases or leptomeningeal disease. This trial is studying Advanced Extrapulmonary Neuroendocrine Carcinoma, Metastatic Extrapulmonary Neuroendocrine Carcinoma, Recurrent Extrapulmonary Neuroendocrine Carcinoma, Unresectable Extrapulmonary Neuroendocrine Carcinoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures overall survival, which means it tracks how long patients live after starting the treatment. The specific primary outcome measures are: Overall survival (From date of registration or from date of start of observation/maintenance therapy to date of death due to any cause, assessed up to 5 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to improve survival and quality of life for patients with advanced neuroendocrine carcinomas by combining immunotherapy with standard chemotherapy. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Advanced Extrapulmonary Neuroendocrine Carcinoma, Metastatic Extrapulmonary Neuroendocrine Carcinoma, Recurrent Extrapulmonary Neuroendocrine Carcinoma, Unresectable Extrapulmonary Neuroendocrine Carcinoma, where improved treatment options are needed.

Investor Insight

The large market size and high unmet need in neuroendocrine cancers suggest a strong potential for approval and commercial success. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you have any history of severe allergies or if you are currently on any other cancer treatments. Participation involves regular IV infusions and scans, so discuss the schedule with your healthcare provider. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 189 participants

Interventions

• BIOLOGICAL: Atezolizumab — Given IV
• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• DRUG: Carboplatin — Given IV
• DRUG: Cisplatin — Given IV
• PROCEDURE: Computed Tomography — Undergo CT scan

Primary Outcomes

• Overall survival (From date of registration or from date of start of observation/maintenance therapy to date of death due to any cause, assessed up to 5 years)

Secondary Outcomes

• Progression-free survival (From date of registration or start of observation/maintenance therapy to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 5 years)
• Duration of response (Time from date of initial response to date of progression or death, assessed up to 5 years)
• Objective response rate (confirmed complete response [CR] or partial response [PR]) (Up to 5 years from study enrollment)
• Clinical benefit rate (confirmed CR or PR of any amount of time or stable disease for 6 months or longer) (Up to 5 years from study enrollment)

Full Eligibility Criteria

Inclusion Criteria:

* Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, neuroendocrine carcinoma (NEC)
* Participants must have disease that is unresectable or metastatic and not eligible for definitive therapy as deemed per the treating investigator
* Participants must have radiologically evaluable disease, measurable or non-measurable, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. All measurable and nonmeasurable lesions must be assessed by CT scan with IV contrast of the chest/abdomen/and pelvis (or CT chest without contrast and MRI abdomen/pelvis with gadolinium contrast, if contraindication to CT iodinated contrast) within 28 days prior to registration. While may be used for routine clinical evaluation, PET scans and bone scans alone are not acceptable for disease assessment while participating in this study. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form
* Participants must have brain MRI (or CT head with contrast if there is contraindication to MRI brain) if clinically indicated within 28 days prior to registration. Note: Brain imaging is not required in participants without known and/or clinical concern for brain metastases. Participants with asymptomatic central nervous system (CNS) metastases are eligible if one or more of the following apply:

  * Participants who have received treatment for brain metastases must have:

    * No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
    * Discontinued all corticosteroids at least 14 days prior to registration
  * Participants with treatment-naive brain lesions must have:

    * No lesion measuring \> 2.0 cm in size in any axis
    * MRI brain or CT head with contrast (if there is contraindication to MRI brain) demonstrating no evidence for mass effect, edema, or other impending neurological compromise within 28 days prior to registration
    * No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
    * No need for \> 2 mg of dexamethasone (or equivalent of \> 10 mg prednisone) per day at time of registration
* Participants must not have symptomatic central nervous system (CNS) metastases
* Participants must not have known or suspected leptomeningeal disease
* Participants with prior history of non-metastatic (localized/locally advanced disease) extrapulmonary poorly differentiated NEC may have had prior platinum-based therapy +/- radiation +/- surgery provided that all therapy was completed \>= 6 months prior to registration
* Participants must discontinue denosumab prior to study registration and plan to replace with a bisphosphonate while on the study
* Participants must not have had prior treatment for advanced or metastatic NEC EXCEPT one cycle of platinum (carboplatin/cisplatin) + etoposide is allowed prior to registration. Other chemotherapy regimens are not allowed. For participants with prostate or urothelial NEC, prior chemotherapy for the non-NEC component (e.g. adenocarcinoma or urothelial) is allowed as long as such therapy was completed \>= 24 weeks prior to registration and participants have recovered from all prior toxicities to =\< grade 1.
* Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, antiPD-L2, CD137 agonists, anti-CTLA-4 agent, or any other immune checkpoint inhibitors for any neuroendocrine neoplasm. Immune checkpoint inhibitors given for other cancer indications are allowed provided last therapy was given at least 12 months prior to study registration
* Participants must not have received treatment with systemic immunostimulatory agents including, but not limited to, interferon and interleukin2 \[IL-2\] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to registration
* Participants must not have had history of known severe allergy, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, including to Chinese hamster ovary cell products or to any component of the atezolizumab formulation, cisplatin, carboplatin, or etoposide
* Participants must not be on active systemic therapy for another cancer with the exception of hormonal therapy including androgen deprivation therapy (e.g., gonadotropin-releasing hormone \[GnRH\] agonists or antagonists), which can be continued while participants are receiving protocol therapy. Use of enzalutamide or apalutamide is permitted after completion of chemotherapy and must be held during chemotherapy for participants receiving prior to enrollment. Use of darolutamide is permitted during chemotherapy. Glucocorticoid-containing regimens, including abiraterone, are not permitted.
* Participants must be \>= 18 years of age
* Participants must have a Zu

Trial Locations

• Alaska Women's Cancer Care, Anchorage, Alaska, United States
• Cancer Center at Saint Joseph's, Phoenix, Arizona, United States
• Mayo Clinic Hospital in Arizona, Phoenix, Arizona, United States
• Kaiser Permanente-Anaheim, Anaheim, California, United States
• Sutter Auburn Faith Hospital, Auburn, California, United States
• Sutter Cancer Centers Radiation Oncology Services-Auburn, Auburn, California, United States
• Kaiser Permanente-Baldwin Park, Baldwin Park, California, United States
• Kaiser Permanente-Bellflower, Bellflower, California, United States
• Alta Bates Summit Medical Center-Herrick Campus, Berkeley, California, United States
• Sutter Cancer Centers Radiation Oncology Services-Cameron Park, Cameron Park, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Small cell lung cancer, large cell neuroendocrine carcinoma, carcinoid tumors, Merkel cell carcinoma, and other neuroendocrine tumors.

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