Immunotherapy in combination with chemotherapy in small-cell lung cancer.

Phase 1

• Conditions: Advanced small-cell lung cancer; MedDRA version: 27.0Level: PTClassification code 10059514Term: Small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004784-12-GR
• Lead Sponsor: Hellenic Cooperative Oncology Group (HeCOG)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-03-13
• Last Update Posted: 18 June 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 55

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

•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 (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication, are exclusion criteria.
•Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified