Clinical trial NCT03568097: Immunotherapy in Combination With Chemotherapy in Small-cell Lung Cancer
Official title: Phased Avelumab Combined With Chemotherapy as First-line Treatment for Patients With Advanced Small-cell Lung Cancer (SCLC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Small Cell Lung Carcinoma
Lead sponsor: Hellenic Cooperative Oncology Group
Sponsor class: OTHER
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2018-06-26
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: PAVE(Phased Avelumab combined with chemotherapy as first-line treatment for patients with advanced small-cell lung cancer) is a Greek, investigator- initiated, single arm open- label phase II study of Avelumab in combination with cisplatin or carboplatin/ etoposide.

The study will include an initial safety run-in, open-label, singlearm part (Part 1), and the actual phase II study (Part 2). The total number of patients will not change (the safety run-in patients will be included in the final total number of participants). The safety run-in period will not alter the total study timelines, as phase II accrual will follow immediately after the safety run-in.

Detailed description: Advanced small cell lung cancer (SCLC) remains a disease with dismal prognosis and new therapeutics are urgently needed. SCLC is notably chemosensitive and first-line chemotherapy with platinum analogs and etoposide is associated with high rates of initial objective responses that unfortunately do not last long.

The primary endpoint for study design is 1-year PFS rate, where according to RECIST v1.1 PFS is determined as the time from the date of study entry to the date of progression, death from any cause or date of last contact.Secondary End Point is the evaluation of efficacy of the study treatment in terms of Overall Survival (OS), Best Overall Response (BOR), Objective Response Rate (ORR) and Duration of Response (DOR).

Evaluation of the safety of the study treatment by assessing Treatment-Emergent Adverse Events (TEAEs).

Evaluation of the Quality of Life of patients receiving the study the study treatment. Evaluation of potential biomarkers on fresh or archival sample,of formalin-fixed paraffin embedded tumor tissue block or a minimum of 10 unstained tumor tissue sections. Moreover 10 ml of EDTA-stored blood sample will be collected as well.

Eligibility 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.

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.
* 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, history of anaphylaxis, or uncontrolled 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 prior organ transplantation including allogenic stem-cell transplantation are excluded.
* Patients with an active infection requiring systemic therapy are excluded.
* Patients with known history of testing positive for HIV or known acquired immunodeficiency syndrome are excluded.
* 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)
* Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.
* Persisting toxicity related to prior therapy
* Other severe acute or chronic medical conditions.

Primary outcomes:
measure: 1- year Progression Free Survival (PFS) Rate
timeFrame: Time from inclusion in the trial up to 12 months
Secondary outcomes:
measure: Overall Survival Time (OS)
timeFrame: Time from inclusion in the trial until the date of death due to any cause, up to 30 months.
measure: Best Overall Response (BOR).
timeFrame: Time from inclusion in the trial up to 30 months.
measure: Objective Response Rate (ORR).
timeFrame: Time from inclusion in the trial up to 30 months.
measure: Duration of Response (DOR) according to RECIST Version 1.1
timeFrame: Time from inclusion in the trial up to 30 months.
measure: 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
timeFrame: From the first dose of study drug treatment up to 90 days after the last dose of study drug administration
measure: Change from baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire
timeFrame: On Day 1 every 21 days for 18 weeks then monthly up to 30 months.
measure: Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status
timeFrame: On Day 1 every 21 days for 18 weeks then monthly up to 30 months.
measure: Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)
timeFrame: On Day 1 every 21 days for 18 weeks then monthly up to 30 months.
measure: Translational research
timeFrame: At baseline
Other outcomes:
Locations:
city: Chaïdári
country: Greece
facility: Attikon University Hospital
state: Athens
city: Néa Kifisiá
country: Greece
facility: Agii Anargiri Cancer Hospital
state: Athens
city: Néo Fáliro
country: Greece
facility: Metropolitan Hospital
state: Athens
city: Río
country: Greece
facility: Patra University Hospital
state: Patra
city: Athens
country: Greece
facility: Henry Dunant Hospital Center
city: Athens
country: Greece
facility: Alexandra Hospital
Study officials:
affiliation: 1st Department on Medical Oncology, Metropolitan Hospital
name: Helena Linardou, MD
role: PRINCIPAL_INVESTIGATOR
References: