Advanced small-cell lung cancer MedDRA version: 27.0 Level: PT Classification code 10059514 Term: Small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Bavencio 20 mg/ml concentrate for solution for infusion
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AVELUMAB
CAS Number: 1537032-82-8
Concentration unit
Sponsors
Hellenic Cooperative Oncology Group (HeCOG)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Signed written informed consent •Male or female patients aged more than or equal to (=) 18 years •With Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry •At least 1 measurable tumor lesion by RECIST 1.1 •With histologically confirmed metastatic (Stage IV) small cell lung cancer (SCLC) •Patients must not have received any previous systemic treatment for small cell lung cancer •Patients must have an estimated life expectancy of more than 12 weeks •Patients must have an available recently-obtained, formalin-fixed, paraffin-embedded (FFPE) tissue sample containing tumor (biopsy preferably within 6 months) or a minimum number of 10 unstained slides, suitable for PD-L1 expression assessment. PHYSIOLOGIC FUNCTION: •Hematologic: Absolute neutrophil count (ANC) = 1.5 × 109/L, platelet count = 100 × 109/L, and hemoglobin = 9 g/dL (may have been transfused) •Hepatic: Total bilirubin level = 1.5 × the upper limit of normal (ULN) range and AST and ALT levels = 2.5 × ULN or AST and ALT levels = 5 x ULN (for subjects with documented metastatic disease to the liver. •Renal: Estimated creatinine clearance = 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) PREGNANCY AND CONTRACEPTION •Pregnancy test: Negative serum or urine pregnancy test at screening for women of childbearing potential. •Contraception: Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last avelumab treatment administration or at least 6 months after the last dose of cisplatin/carboplatin or etoposide administration, if the risk of conception exists. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: •Patients with brain metastases are excluded, except those with brain metastases that have been treated with surgery or radiation and are clinically stable for at least 2 weeks prior to registration. Subjects must be either off steroids or on a stable or decreasing dose of =10 mg daily prednisone (or equivalent), and should not have ongoing neurological symptoms that are related to the brain disease. •Prior therapy with any antibody or drug targeting T cell co-regulatory proteins, concurrent anticancer treatment, or immunosuppressive agents •Patients on current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses = 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).” •Known severe hypersensitivity reactions to monoclonal antibodies (Grade = 3 NCI CTCAE v 4.03), history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma), and persisting toxicity related to prior therapy of Grade > 1 NCI-CTCAE v 4.03. •Patients with active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. •Patients with prior organ transplantation including allogenic stem-cell transplantation are excluded. •Patients with an active infection requiring systemic therapy are excluded. •Patients positive for HIV or known acquired immunodeficiency syndrome are excluded. HIV- positive patients with undetectable viral load may be included in the study provided they meet all other inclusion criteria and their HIV care practitioner has consented. •Also excluded are patients with Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).Patients with a recent (pre-enrollment) HBV negative viral load may be eligible for the study if they meet all the other inclusion criteria and HBV or HCV infection is remitted with or without antiviral treatment based on written proof by the treating hepatologist. •Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines. •Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke ( 1); however, alopecia, sensory neuropathy Grade = 2, or other Grade = 2 not constituting a safety risk based on investigator’s judgment are acceptable. •Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and efficacy of phased avelumab administration along with first-line chemotherapy for patients with advanced small-cell lung cancer, primarily by determining whether phased avelumab administration and maintenance treatment could prolong Progression-Free Survival (PFS) and 1-year PFS.;Secondary Objective: •Overall Survival (OS). •Best Overall Response (BOR). BOR will be determined according to RECIST 1.1. •Objective Response Rate (ORR). •Duration of Response (DOR). •Change from Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire •Change from Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status. •Change from Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) •Number of Subjects with Treatment-Emergent Adverse Events (TEAEs) According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. •Translational research studies will be conducted for PD-L1 expression as well as for other possible biomarkers on biological material collected for the study.;Primary end point(s): To evaluate the Progression-Free Survival rate at 1 year (1-year PFS) and the Progression-Free Survival (PFS).;Timepoint(s) of evaluation of this end point: Tumor assessments should occur every 6 weeks (±14 days) up to Week 48, then every 12 weeks until documented radiologic disease progression. Patients with a history of brain metastasis must have surveillance MRI approximately every 12 weeks from the date of first dose, or sooner if clinically indicated. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •To evaluate the efficacy of the study treatment in terms of Overall Survival (OS), Best Overall Response (BOR), Objective Response Rate (ORR) and Duration of Response (DOR). •To evaluate the safety of the study treatment by assessing Treatment-Emergent Adverse Events (TEAEs). •To evaluate the Quality of Life of patients receiving the study the study treatment •To evaluate potential biomarkers on fresh or archival sample,of formalin-fixed paraffin embedded tumor tissue block or a minimum of 10 unstained tumor tissue sections . 10 ml of EDTA-stored blood sample will be collected as well. ;Timepoint(s) of evaluation of this end point: 1.Tumor assessments should occur every 6 weeks (±714days) up to Week 48, then every 12 weeks until documented radiologic disease progression. Patients with a history of brain metastasis must have surveillance MRI approximately every 12 weeks from the date of first dose, or sooner if clinically indicated. 2.Assessment of Adverse Events will be performed in every cycle throughout the treatment. 3.All QoL tools will be completed on Day 1 of each Cycle. Thereafter in Maintenance phase it will be completed every 2 Cycles (once a month)- the QoL assessment will be performed PRIOR to any study procedures and treatment. 4.In screening period | — |
Countries
Greece
Contacts
Public ContactClinical Trials
Hellenic Cooperative Oncology Group (HeCOG)
Outcome results
None listed