A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer
- Conditions
- Small Cell Lung Carcinoma
- Registration Number
- NCT03850067
- Lead Sponsor
- Celgene
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 90
Inclusion Criteria:<br><br> 1. Male and female subject is 18 years of age or older at the time of signing the<br> informed consent form (ICF).<br><br> 2. Subject with histological or cytological confirmation of extensive stage SCLC<br> according to 2015 WHO classification (Travis, 2015).<br><br> 3. Subject must be able to provide fresh or archival tumor tissues<br><br> 4. Subject is found suitable for at least 4 cycles of platinum-based standard<br> chemotherapy.<br><br> 5. Subject has at least 1 site of measurable disease per RECIST 1.1.<br><br> 6. Subject must have the following laboratory values:<br><br> • Absolute neutrophil count (ANC) = 1.5 x 109/L<br><br> • Hemoglobin (Hgb) = 10 g/dL (= 100 g/L or > 6.2 mmol/L)<br><br> - Platelet count (Plt) = 150 x 109/L<br><br> - Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase<br> (AST/SGOT) and alanine aminotransferase/serum glutamate pyruvate transaminase<br> (ALT/SGPT) = 3.0 x upper limit of normal (ULN) or = 5.0 x ULN if liver<br> metastases are present<br><br> - Serum total bilirubin = 1.5 x ULN<br><br> - Serum creatinine = 1.5 mg/dL or creatinine clearance = 60 mL/min (see Appendix<br> G to see creatinine clearance formula). For the purposes of this protocol, the<br> glomerular filtration rate (GFR) is considered to be equivalent to the<br> creatinine clearance.<br><br> - Prothrombin time (or international normalized ratio [INR]) and activated<br> partial thromboplastin time (APTT) = 1.5 ULN<br><br> 7. Females of childbearing potential (FCBP) must:<br><br> • Either commit to true abstinence from heterosexual contact (which must be reviewed<br> on a monthly basis and source documented) or agree to use one highly effective<br> contraceptive method plus one barrier method.<br><br> - Have two negative pregnancy tests as verified by the Investigator prior to<br> starting CC-90011:<br><br> - a negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at<br> Screening<br><br> - a negative serum or urine pregnancy test within 24 hours prior to Cycle 1<br> Day 1 of study treatment.<br><br> - a negative Serum or urine within 24 hours prior to first dose of nivolumab<br> and then every 4 weeks (± 1 week) regardless of dosing schedule.<br><br> - Avoid conceiving for 6 months after last dose of cisplatin or carboplatin or<br> etoposide, or 5 months after last dose of nivolumab for FCBP, or 45 days after<br> the last dose of CC-90011, whichever is the latest.<br><br> - Agree to ongoing pregnancy testing during the course of the study, and after<br> the end of study treatment. This applies even if the subject practices true<br> abstinence from heterosexual contact.<br><br> 8. Males must practice true abstinence from heterosexual intercourse (which must be<br> reviewed on a monthly basis) or agree to use a condom (a latex condom is<br> recommended) during sexual contact with a pregnant female or an FCBP and will avoid<br> conceiving from signing the ICF, while participating in the study, during dose<br> interruptions, and for 6 months after last dose of cisplatin, or carboplatin, or<br> etoposide or at least 105 days following CC-90011 discontinuation, whichever is the<br> latest, even if he has undergone a successful vasectomy.<br><br> 9. Males must agree to refrain from donating sperm while on treatment and females must<br> agree to refrain from donating ova while on treatment and for 6 months after the<br> last dose of cisplatin or etoposide or 105 days after last dose of CC-90011.<br><br> 10. Subject is able to swallow pills.<br><br>Exclusion Criteria:<br><br> 1. Subject has received anticancer therapy (either approved or investigational,<br> including radiation with curative intent) for SCLC prior to study entry.<br><br> 2. Subject has undergone major surgery = 4 weeks prior to Cycle 1 Day 1 or has not<br> recovered from surgery.<br><br> 3. Subject has persistent diarrhea due to a malabsorptive syndrome (such as celiac<br> sprue or inflammatory bowel disease) = NCI CTCAE Grade 2, despite medical<br> management), or any other significant gastrointestinal (GI) disorder that could<br> affect the absorption of CC- 90011.<br><br> 4. Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly<br> those with a history of and/or risk of perforation and GI tract hemorrhages.<br><br> 5. Subject with any hemorrhage/bleeding event > CTCAE Grade 2 or hemoptysis > 1<br> teaspoon within 4 weeks prior to the first dose.<br><br> 6. Subject with symptomatic and untreated or unstable central nervous system (CNS)<br> metastases.<br><br> 7. Subject has impaired cardiac function or clinically significant cardiac diseases,<br> including any of the following:<br><br> - Left ventricular ejection fraction (LVEF) < 45% as determined by multigated<br> acquisition (MUGA) scan or echocardiogram (ECHO).<br><br> - Complete left bundle branch or bifascicular block.<br><br> - Congenital long QT syndrome.<br><br> - Persistent or clinically meaningful ventricular arrhythmias or atrial<br> fibrillation.<br><br> - QTcF = 480 msec on Screening ECG (mean of triplicate recordings).<br><br> 8. Subject has other clinically significant heart disease such as congestive heart<br> failure requiring treatment or uncontrolled hypertension (blood pressure = 160/95 mm<br> Hg).<br><br> 9. Subject is a pregnant or nursing female.<br><br> 10. Subject has known human immunodeficiency virus (HIV) infection.<br><br> 11. Subject has known chronic active hepatitis B or C virus (HBV, HCV) infection.<br><br> 12. Subject with ongoing treatment with chronic, therapeutic dosing of anticoagulants<br> (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors, thrombin<br> antagonist).<br><br> 13. Subject has a history of concurrent second cancers requiring active, ongoing<br> systemic treatment.<br><br> 14. Subject has Grade 2 peripheral sensory neuropathy.<br><br> 15. Subject with poor bone marrow reserve as assessed by Investigator.<br><br> 16. Subject has any condition including the presence of laboratory abnormalities, which<br> places the subject at unacceptable risk if he/she were to participate in the study.<br><br> 17. Subject has any significant medical condition, laboratory abnormality, or<br> psychiatric illness that would prevent the subject from participating in the study.<br><br> 18. Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or<br> 20 days for severe/critical illness prior to C1D1.<br><br> • Acute symptoms must have resolved and based on investigator assessment in<br> consultation with the medical monitor, there are no sequelae that would place the<br> participant at a higher risk of receiving study treatment<br><br> 19. Previous SARS-CoV-2 vaccine within 7 days of C1D1. For vaccines requiring more than<br> one dose, the full series (e.g. both doses of a two-dose series) should be completed<br> prior to C1D1 when feasible and when a delay in C1D1 would not put the study subject<br> at risk<br><br> 20. Subject has any condition that confounds the ability to interpret data from the<br> study.<br><br> For the subjects treated with nivolumab:<br><br> 21. Subject has received prior therapies targeting PD-1 or PD-L1<br><br> 22. Subject has a history of persistent skin rash = NCI CTCAE Grade 2.<br><br> 23. Subject with an autoimmune diseas
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Dose-Limiting Toxicity (DLT);Maximum Tolerated Dose (MTD);Adverse Events (AEs)
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR);Progression-free Survival (PFS);Overall Survival (OS);Pharmacokinetics- Cmax;Pharmacokinetics- AUC;Pharmacokinetics- Tmax;Pharmacokinetics- t1/2;Pharmacokinetics- CL/F;Pharmacokinetics- VzF