Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Carcinoma

Carcinoma, Neuroendocrine

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Dermatologic Agents

Atezolizumab

Carboplatin

Etoposide

Cisplatin

Immunomodulating Agents

Etoposide phosphate

Podophyllotoxin

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Enzyme Inhibitors

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

Keratolytic Agents

Tubulin Modulators

Antimitotic Agents

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.

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.

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.

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Patient Observation

Site Public Contact

Shahzad Siddique

Helen H. Moon

Deepti Behl

Nadine G. Mikhaeel-Kamel

Matthew Austin

Tareq Al Baghdadi

Mintallah Haider

Elizabeth S. Nakasone

Bryan A. Faller

Mary F. Mulcahy

Ardaman Shergill

Vamsi K. Vasireddy

Mark F. Kozloff

Joseph J. Merchant

Richard L. Deming

Joshua Lukenbill

Marshall P. Stagg

Tara Castellano

David B Zhen

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.

PRIMARY OBJECTIVES:

I. Compare the combination of induction platinum/etoposide and atezolizumab followed by maintenance atezolizumab (Arm 1) versus induction platinum/etoposide alone (Arm 3).

II. Compare the combination of induction platinum/etoposide and atezolizumab followed by observation (Arm 2) versus induction platinum/etoposide alone (Arm 3).

III. Compare the combination of induction platinum/etoposide and atezolizumab followed by maintenance atezolizumab (Arm 1) versus the combination of induction platinum/etoposide and atezolizumab followed by observation (Arm 2).

SECONDARY OBJECTIVES:

I. To compare overall survival (OS), measured from start of observation/maintenance, across arms.

II. To compare progression free survival (PFS) (measured from randomization and measured from start of observation/maintenance) across arms.

III. To compare objective response rate (ORR = confirmed and unconfirmed partial response \[PR\] + confirmed and unconfirmed complete response \[CR\]) across arms among patients with measurable disease at randomization.

IV. To compare clinical benefit rate (CBR = confirmed and unconfirmed PR + confirmed and unconfirmed CR + stable disease \[SD\]) across arms among patients with measurable disease at randomization.

V. To compare duration of response (DOR) across arms. VI. To evaluate the safety and tolerability of each arm.

ADDITIONAL OBJECTIVE:

I. To bank tumor and blood samples for future biomarker correlative studies.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: During induction phase, patients receive atezolizumab intravenously (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.

ARM II: 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.

ARM III: 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 in all arms also undergo compute tomography (CT) scan and/or magnetic resonance imaging (MRI) throughout the trial and blood sample collection on study.

After completion of study treatment, patients are followed up for 5 years.

Evaluating the Addition of the Immunotherapy Drug Atezolizumab to Standard Chemotherapy Treatment for Advanced or Metastatic Neuroendocrine Carcinomas That Originate Outside the Lung

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

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Log-rank tests stratified by the randomization stratification factors will be used for null hypothesis (efficacy) tests. Cox regression models stratified by the randomization stratification factors will be used for alternative hypothesis (futility) tests.

Will be estimated using the Kaplan-Meier method and compared using log-rank tests.

Will be estimated non-parametrically using cumulative incidence curves.

Will be tabulated and compared between arms using Fisher's exact test.

National Cancer Institute (NCI)

Spots Global Cancer Trial Database for advanced extrapulmonary neuroendocrine carcinoma