Trial record 5 of 6 for:
S2012
Evaluating the Addition of the Immunotherapy Drug Atezolizumab to Standard Chemotherapy Treatment for Advanced or Metastatic Neuroendocrine Carcinomas That Originate Outside the Lung
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| ClinicalTrials.gov Identifier: NCT05058651 |
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Recruitment Status :
Recruiting
First Posted : September 28, 2021
Last Update Posted : May 31, 2023
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Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced Extrapulmonary Neuroendocrine Carcinoma Metastatic Extrapulmonary Neuroendocrine Carcinoma Recurrent Extrapulmonary Neuroendocrine Carcinoma Unresectable Extrapulmonary Neuroendocrine Carcinoma | Biological: Atezolizumab Procedure: Biospecimen Collection Drug: Carboplatin Drug: Cisplatin Procedure: Computed Tomography Drug: Etoposide Procedure: Magnetic Resonance Imaging Other: Patient Observation | Phase 2 Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 189 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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) |
| Actual Study Start Date : | December 2, 2021 |
| Estimated Primary Completion Date : | October 31, 2024 |
| Estimated Study Completion Date : | October 31, 2024 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I (atezolizumab, platinum drug, etoposide)
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.
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Biological: Atezolizumab
Given IV
Other Names:
Procedure: Biospecimen Collection Undergo blood sample collection
Other Names:
Drug: Carboplatin Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Procedure: Computed Tomography Undergo CT scan
Other Names:
Drug: Etoposide Given IV
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
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Experimental: Arm II (atezolizumab, platinum drug, etoposide, observation)
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.
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Biological: Atezolizumab
Given IV
Other Names:
Procedure: Biospecimen Collection Undergo blood sample collection
Other Names:
Drug: Carboplatin Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Procedure: Computed Tomography Undergo CT scan
Other Names:
Drug: Etoposide Given IV
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Other: Patient Observation Undergo observation
Other Names:
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Active Comparator: Arm III (platinum drug, etoposide, observation)
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.
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Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Drug: Carboplatin Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Procedure: Computed Tomography Undergo CT scan
Other Names:
Drug: Etoposide Given IV
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Other: Patient Observation Undergo observation
Other Names:
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Primary Outcome Measures :
- Overall survival [ 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 ]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.
Secondary Outcome Measures :
- Progression-free survival [ 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 ]Will be estimated using the Kaplan-Meier method and compared using log-rank tests.
- Duration of response [ Time Frame: Time from date of initial response to date of progression or death, assessed up to 5 years ]Will be estimated non-parametrically using cumulative incidence curves.
- Objective response rate (confirmed complete response [CR] and partial response [PR]) [ Time Frame: Up to 5 years from study enrollment ]Will be tabulated and compared between arms using Fisher's exact test.
- Clinical benefit rate (confirmed CR or PR of any amount of time or stable disease for 6 months or longer) [ Time Frame: Up to 5 years from study enrollment ]Will be tabulated and compared between arms using Fisher's exact test.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, neuroendocrine carcinoma (NEC) 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 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
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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:
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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
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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
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- 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 be >= 18 years of age
- Participants must have a Zubrod performance status of =< 2 within 28 days prior to registration
- Participants must have a complete medical history and physical exam within 28 days prior to registration
- Absolute neutrophil count (ANC) >= 1.5 x 10^9 /L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
- Hemoglobin >= 9.0 g/dl (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
- Platelet count >= 100 x 10^9/L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
- Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
- Serum total bilirubin =< 1.5 x ULN (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
- Measured creatinine clearance (CL) > 50 mL/min or calculated creatinine CL > 50 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
- Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load, with testing performed as clinically indicated
- Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment must have an undetectable HCV viral load, with testing performed as clinically indicated
- Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable HIV viral load within 6 months of registration
- Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
- Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
Exclusion Criteria:
- Participants must not have symptomatic central nervous system (CNS) metastases
- Participants must not have known or suspected leptomeningeal disease
- 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, anti-PD-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 not have uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN) within 14 days prior to registration. Participants who have asymptomatic hypercalcemia are eligible provided that medical therapy to treat the hypercalcemia is planned
- Participants must not have a diagnosis of immunodeficiency nor be receiving systemic steroid therapy (equivalent of > 20 mg of hydrocortisone per day) or any other form of immunosuppressive therapy within 14 days prior to registration
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Participants must not have active or history of autoimmune disease or immune deficiency, including, but not limited to myasthesia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener grandulomatosis, Sjogren syndrome, Guillian-Barre syndrome, or multiple sclerosis with the following exceptions:
- Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study
- Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
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Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
- Rash must cover < 10% of body surface area
- Disease is well controlled at baseline and requires only low-potency topical corticosteroids
- No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
- Participants must not have history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Participants must not have significant cardiovascular disease, such as New York Heart Association class II or greater cardiac disease, myocardial infarction within 3 months prior to registration, unstable arrythmias, or unstable angina
- Participants must not have had a major surgical procedure other than for diagnosis within 28 days prior to registration. Participant must not plan to receive a major surgical procedure during the course of protocol treatment. NOTE: Patient port placement is not considered a major surgery
- Participants must not have severe infections (i.e., Common Terminology Criteria for Adverse Events [CTCAE] grade >= 2) at time of registration, including but not limited to hospitalization for complications for infection, bacteremia, or severe pneumonia
- Participants must not have active tuberculosis
- Participants must not have prior allogeneic bone marrow transplantation or solid organ transplant
- Participants must not have received administration of a live, attenuated vaccine (e.g., FluMist [registered trademark]) within 28 days prior to initiation of study treatment, during treatment with atezolizumab, and not plan to receive for 5 months after the last dose of atezolizumab
- Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method (with details provided as a part of the consent process) during the treatment period and for 5 months after the final dose of atezolizumab. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05058651
Locations
Show 122 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | David B Zhen | SWOG Cancer Research Network |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT05058651 |
| Other Study ID Numbers: |
NCI-2021-09851 NCI-2021-09851 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) S2012 ( Other Identifier: SWOG ) S2012 ( Other Identifier: CTEP ) U10CA180888 ( U.S. NIH Grant/Contract ) |
| First Posted: | September 28, 2021 Key Record Dates |
| Last Update Posted: | May 31, 2023 |
| Last Verified: | January 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | 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. |
| URL: | https://grants.nih.gov/policy/sharing.htm |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Carcinoma Carcinoma, Neuroendocrine Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Adenocarcinoma Neoplasms, Nerve Tissue Cisplatin Carboplatin Etoposide Etoposide phosphate Atezolizumab |
Podophyllotoxin Antibodies, Monoclonal Antineoplastic Agents Antineoplastic Agents, Phytogenic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Immune Checkpoint Inhibitors Antineoplastic Agents, Immunological Immunologic Factors Physiological Effects of Drugs Keratolytic Agents Dermatologic Agents Tubulin Modulators |