Evaluating the Addition of the Immunotherapy Drug Atezolizumab to Standard Chemotherapy Treatment for Advanced or Metastatic Neuroendocrine Carcinomas That Originate Outside the Lung
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.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
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
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
Disqualifiers
None
Trial design
Design model
Parallel
Treatments tested in this trial
Atezolizumab
Biological/Vaccine
Given IV
Biospecimen Collection
Procedure/Surgery
Undergo blood sample collection
Carboplatin
Drug
Given IV
Cisplatin
Drug
Given IV
Computed Tomography
Procedure/Surgery
Undergo CT scan
Etoposide
Drug
Given IV
Magnetic Resonance Imaging
Procedure/Surgery
Undergo MRI
Patient Observation
Other intervention
Undergo observation
Treatment groups
189 Participants
are divided into 3 treatment groups
Group A: Arm I (atezolizumab, platinum drug, etoposide)Experimental treatment 7 interventions
Group B: Arm II (atezolizumab, platinum drug, etoposide, observation)Experimental treatment 8 interventions
Group C: Arm III (platinum drug, etoposide, observation)Active comparator 7 interventions
Trial outcomes
Primary outcomes
1
Overall survival
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.
Time frame
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
1
Progression-free survival
Will be estimated using the Kaplan-Meier method and compared using log-rank tests.
Time frame
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
2
Duration of response
Will be estimated non-parametrically using cumulative incidence curves.
Time frame
Time from date of initial response to date of progression or death, assessed up to 5 years
