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Cisplatin/Carboplatin and Etoposide With or Without Nivolumab in Treating Patients With Extensive Stage Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT03382561
Recruitment Status : Active, not recruiting
First Posted : December 26, 2017
Last Update Posted : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This randomized phase II clinical trial studies whether the addition of nivolumab to cisplatin (or carboplatin) and etoposide will improve outcomes when treating patients with extensive stage small cell lung cancer. Drugs used in chemotherapy such as cisplatin, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cisplatin/carboplatin and etoposide together with nivolumab may work better in treating patients with extensive stage small cell lung cancer.

Condition or disease Intervention/treatment Phase
Extensive Stage Lung Small Cell Carcinoma Recurrent Small Cell Lung Carcinoma Drug: Carboplatin Drug: Cisplatin Drug: Etoposide Other: Laboratory Biomarker Analysis Biological: Nivolumab Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival (PFS) of patients with extensive stage small cell lung cancer (ED-SCLC) treated with cisplatin/carboplatin and etoposide (CE) or CE with nivolumab (CEN) as front-line treatment.

SECONDARY OBJECTIVES:

I. To estimate overall survival of patients with ED-SCLC treated with cisplatin/carboplatin and etoposide (CE) or CE with nivolumab (CEN) as front-line treatment.

II. To assess best overall response rate after treatment with CE with or without nivolumab as first line treatment.

III. To evaluate the toxicity profile of nivolumab with CE.

TERTIARY OBJECTIVES:

I. To evaluate immune biomarkers and biomarkers correlatives. II. To evaluate serial circulating tumor deoxyribonucleic acid (DNA) and explore whether clinical outcome is associated with fluctuations in DNA levels following the administration of therapy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1, carboplatin IV over 30-60 minutes on day 1 or cisplatin IV over 60-120 minutes on day 1, and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients continue to receive nivolumab IV over 30 minutes every 2 weeks for up to 2 years.

ARM B: Patients receive carboplatin IV over 30-60 minutes on day 1 or cisplatin IV over 60-120 minutes on day 1, and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months if the patient is less than 2 years from registration, every 6 months if the patient is 2-3 years from registration, and yearly for up to 5 years from study enrollment.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Clinical Trial of Cisplatin/Carboplatin and Etoposide (CE) Alone or in Combination With Nivolumab as Frontline Therapy for Extensive Stage Small Cell Lung Cancer (ED-SCLC)
Actual Study Start Date : May 2, 2018
Estimated Primary Completion Date : June 2, 2020
Estimated Study Completion Date : June 2, 2020


Arm Intervention/treatment
Experimental: Arm A (nivolumab, CE)
Patients receive nivolumab IV over 30 minutes on day 1, carboplatin IV over 30-60 minutes on day 1 or cisplatin IV over 60-120 minutes on day 1, and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients continue to receive nivolumab IV over 30 minutes every 2 weeks for up to 2 years.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Active Comparator: Arm B (CE)
Patients receive carboplatin IV over 30-60 minutes on day 1 or cisplatin IV over 60-120 minutes on day 1, and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. Progression free survival [ Time Frame: From randomization to documented disease progression or death from any cause, whichever occurs first, assessed up to 5 years ]
    Will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios. Will use a logrank test stratified on the randomization stratification factors with a one-sided type I error rate of 10%.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From randomization to death from any cause, and patients who are thought to be alive at the time of final analysis will be censored at the last date of contact, assessed up to 5 years ]
    Will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios.

  2. Best overall response rate [ Time Frame: Up to 5 years ]
    Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1. Will be compared using Fisher's exact tests with a one-sided type I error rate of 10%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes. Continuous outcomes will be analyzed using Wilcoxon rank sum test, and multivariable linear regression models may be used to adjust for multiple associations with outcome.

  3. Incidence of toxicities [ Time Frame: Up to 5 years ]
    Will be assessed by Common Terminology Criteria for Adverse Events version 5.0 criteria. Will be compared using Fisher's exact tests with a one-sided type I error rate of 10%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes. Continuous outcomes will be analyzed using Wilcoxon rank sum test, and multivariable linear regression models may be used to adjust for multiple associations with outcome.


Other Outcome Measures:
  1. Immune biomarkers and biomarkers correlatives [ Time Frame: Up to 5 years ]
    Will be analyzed for association with subject demographics and/or disease characteristics using the Kruskal Wallis test.

  2. Serial circulating tumor deoxyribonucleic acid (DNA) [ Time Frame: Up to 5 years ]
    Will be analyzed for association with subject demographics and/or disease characteristics using the Kruskal Wallis test.



Information from the National Library of Medicine

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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:

  • Patients must have histologically or cytologically confirmed extensive stage small cell lung cancer and must be a candidate for systemic therapy; NOTE: The extensive disease SCLC classification for this protocol includes all patients with disease sites not defined as limited stage; limited stage disease category includes patients with disease restricted to one hemithorax with regional lymph node metastases, including hilar, ipsilateral and contralateral mediastinal, and/or ipsilateral supraclavicular nodes; extensive disease patients are defined as those patients with extrathoracic metastatic disease, malignant pleural effusion, bilateral or contralateral supraclavicular adenopathy; patients with locally recurrent SCLC who are not eligible for curative intent chemoradiation are eligible
  • Patients must have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Absolute neutrophil count >= 1,500/mm^3 must be obtained =< 7 days prior to protocol registration
  • Platelets >= 100,000/mm^3 must be obtained =< 7 days prior to protocol registration
  • Leukocytes >= 3000/mm^3 must be obtained =< 7 days prior to protocol registration
  • Hemoglobin >= 9 g/dL must be obtained =< 7 days prior to protocol registration
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (except subjects with Gilbert syndrome, who can have total bilirubin < 3 mg/dL) must be obtained =< 7 days prior to protocol registration
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 X institutional upper limit of normal (ULN) (=< 5 X if liver function test [LFT] elevations due to known liver metastases) must be obtained =< 7 days prior to protocol registration
  • Serum creatinine =< 1.5 x ULN or calculated creatinine clearance > 50 mL/min (using the Cockcroft-Gault formula) must be obtained =< 7 days prior to protocol registration
  • Patients are eligible if central nervous system (CNS) metastases are adequately treated and neurological symptoms have returned to baseline or are controlled for at least 2 weeks prior to enrollment; in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent); patients with untreated CNS metastases are eligible if they are not symptomatic and the lesions are less than 1 cm in size
  • Patients cannot have had prior chemotherapy or biologic therapy for small cell lung cancer for front line treatment; patients receiving prior whole brain radiation cannot register within 7 days after completion of radiation, and must have resolved adverse events attributed to radiation to =< grade 1; a 1-week washout is permitted for palliative radiation (=< 2 weeks of radiotherapy) to non-CNS disease
  • Patients who have received prior chemoradiation treatment with chemotherapy regimen including cisplatin or carboplatin/etoposide for limited-stage SCLC are eligible if treated with curative intent at least 6 months since last treatment from diagnosis of extensive-stage SCLC
  • Patients may not be receiving any other investigational agents while on study
  • Patients must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab or other agents used in the study
  • Women must not be pregnant or breast-feeding; breastfeeding must be discontinued or the subject is not eligible for the study; all females of childbearing potential must have a blood test or urine study, with a minimum sensitivity 50 mlU/L or equivalent units of human chorionic gonadotropin (HCG), within 14 days prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time in the preceding 24 consecutive months)
  • Women of childbearing potential (WOCBP) and males who are sexually active with WOCBP must use an accepted and effective method of contraception or abstain from sexual intercourse for at least one week prior to the start of treatment, and continue for 5 months after the last dose of protocol treatment for women of childbearing potential and 7 months after the last dose of protocol treatment for males who are sexually active with WOCBP
  • No prior or current invasive malignancy (except non-melanomatous skin cancer, localized bladder and prostate cancer) unless disease free for a minimum of 2 years (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible);
  • No prior systemic treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways;
  • Patient must not have leptomeningeal disease
  • No patients with an active, known or suspected autoimmune disease and neuromuscular paraneoplastic syndromes including but not limited to myasthenia gravis, Lambert-Eaton myasthenic syndrome, limbic encephalitis, myositis, Guillain-Barre; subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
  • No patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 7 days of randomization; inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
  • No patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
  • Patients must NOT have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, patients are excluded
  • Patients are ineligible if administration of a live, attenuated vaccine within 4 weeks before randomization
  • No history of severe hypersensitivity reaction to any monoclonal antibody or allergy to study drug components;

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): NCT03382561


  Show 784 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Ticiana Leal ECOG-ACRIN Cancer Research Group

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03382561     History of Changes
Other Study ID Numbers: NCI-2017-02367
NCI-2017-02367 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EA5161 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA5161 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
First Posted: December 26, 2017    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Carcinoma
Small Cell Lung Carcinoma
Lung Neoplasms
Carcinoma, Small Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Nivolumab
Etoposide phosphate
Cisplatin
Carboplatin
Etoposide
Podophyllotoxin
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Keratolytic Agents