Pembrolizumab in Untreated Extensive SCLC

NCT02580994 | Completed Phase 2 DMC

• 2 other identifiers: EORTC-1417-LCG2014-003090-42
• Study Type: interventional
• Target: 125
• Locations: 3 countries
• Sites: 18

Brief Summary

This is a multicenter, open-label, two armed, controlled, and randomized phase II trial investigating the activity of pembrolizumab in combination with standard chemotherapy in Extensive Disease (ED)-SCLC.

Conditions

Small Cell Lung Cancer (SCLC)

Keywords

Extended Disease Small Cell Lung Cancer; phase II; randomized; pembrolizumab; cross-over; etoposide; cisplatin; carboplatin; rechallenge

Outcome Measures

Primary Outcomes (1)

• Increase in Progression Free Survival

  6 months

Secondary Outcomes (1)

• Overall Survival

  12 months

Study Arms (2)

Pembrolizumab + chemotherapy

EXPERIMENTAL

Pembrolizumab, in combination with cis/carboplatin and etoposide for 4 cycles intravenous 200mg on day 1 (every 3 weeks), pembrolizumab continued alone as continuation maintenance until progressive disease

Drug: Pembrolizumab; Drug: cis/carboplatin and etoposide

Chemotherapy

ACTIVE COMPARATOR

4 cycles of cis/carboplatin and etoposide

Drug: cis/carboplatin and etoposide

Interventions

Pembrolizumab DRUG

IV infusion at the dose of 200 mg on day 1 every 3 weeks

Also known as: MK-3475, Keytruda

Pembrolizumab + chemotherapy

cis/carboplatin and etoposide DRUG

Cisplatin 80 mg/m2 or Carboplatin Area Under the Curve (AUC) 5 IV infusion on day 1 Etoposide 100 mg/m2 IV infusion on day 1, 2 and 3

Also known as: Platinol, Paraplatin and Etopophos

Chemotherapy; Pembrolizumab + chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed SCLC
• Extended disease according to the criteria of the Veteran's Administration - Lung Cancer Group (VALG): disease extended beyond a hemithorax and the supraclavicular node area. Pleural involvement will be considered as extended disease
• Assessment of adequate tissue availability for Program Cell Death-Ligand 1 (PD-L1) immunohistochemistry testing
• Before patient registration, written informed consent must be given according to International Conference of Harmonization-Good Clinical Practice (ICH-GCP), and national/local regulations
• Tumor assessment performed within 10 days before randomization. Patient may or may not have measurable disease
• Previous palliative brain radiotherapy is allowed if terminated at least 3 weeks before randomization
• Partial or complete response according to RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 after 2 cycles of any platinum-based induction chemotherapy regimen
• Adequate hematopoietic, hepatic and renal function within 10 days before randomization defined as follows:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10E9/L, Hemoglobin (Hb) ≥ 9 g/dL and platelet count ≥ 100 x 10E9/L
• Serum creatinine clearance ≥ 60 mL/min as calculated with Cockcroft-Gault formula
• Bilirubin ≤ 1.5 x Upper Limit Normal (ULN), Alanine Aminotransferase (ALT) (SGTP) and Aspartate Transaminase (AST) (SGOT) ≤ 3 x ULN
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as a PTT is within therapeutic range of intended use of anticoagulants N.B. Lactate Dehydrogenase (LDH) level assessment is mandatory for randomization
• Women of child bearing potential (WOCBP) must have a negative urine or serum pregnancy test within 72 hours before randomization
• Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by investigator, during the study treatment period and for at least 120 days after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.

You may not qualify if:

• Prior systemic therapy for SCLC; previous treatment with platinum and etoposide concomitant with radiotherapy (RT) for limited disease is allowed if terminated at least 1 year before patient randomization
• known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (i.e. without evidence of progression by imaging and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have not received steroids for at least 7 days before randomization
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 3-4 (at registration) (patients who are judged by the investigator to be PS 2 due to primary disease are the only PS 2 patients who are eligible)
• ECOG PS 2-4 (at randomization)
• Less than 3 month life expectancy
• History of interstitial lung disease (ILD) or a history of (non-infectious) pneumonitis that required oral or IV steroids (other than Chronic Obstructive Pulmonary Disease \[COPD\] exacerbation) or current pneumonitis or current evidence of ILD
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs), any replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
• Previous allogeneic tissue/solid organ transplant
• Active infection requiring therapy
• Known history of Human Immunodeficiency Virus (HIV) (known HIV 1/2 antibodies positive). No known active Hepatitis B or C. Active Hepatitis B is defined as a known positive HBsAg results. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative Hepatitis C Virus (HCV) RNA results greater than the lower limits of detection of the assay
• Ongoing grade ≥ 2 peripheral neuropathy
• Prior treatment with platinum, anti-PD-1, anti-PD-L1/2, anti interleukin-7 receptor-alpha (anti-CD127), Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) modulators
• Chronic use of immunosuppressive agents and/or systemic corticosteroids or any use in the 3 days before randomization:
• Corticosteroid use on study for management of pembrolizumab Events of Clinical Interest (ECIs), as pre-medication for the administration of chemotherapies, and/or a pre-medication for contrast allergies/reactions is allowed
• Daily prednisone at doses of 5-7.5 mg is allowed as an example of replacement therapy. Equivalent hydrocortisone doses are also permitted if administered as a replacement therapy

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (18)

Centre Hospitalier d'Avignon - Hopital Duffaut

Avignon, 84902, France

Location

CHU de Brest

Brest, 29200, France

Location

Centre Regional Francois Baclesse

Caen, 14076, France

Location

Centre Hopitalier Intercommunal De Creteil

Créteil, 94010, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Assistance Publique - Hopitaux de Marseille - Hopital Nord

Marseille, 13015, France

Location

Centre Hospitalier D'Annecy

Metz-Tessy, 74370, France

Location

Assistance Publique - Hopitaux de Paris - Hopital Avicenne

Paris, 93009, France

Location

Centre Paul Strauss

Strasbourg, 67065, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Ospedale Cannizzaro

Catania, 95126, Italy

Location

Santa Croce e Carle General Hospital

Cuneo, 12100, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Ospedale San Paolo

Milan, 20142, Italy

Location

Ospedale S. Luigi Gonzaga - Universita Di Torino

Orbassano, 10043, Italy

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital

Sheffield, S10 2SJ, United Kingdom

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

pembrolizumab; Etoposide; Cisplatin; Carboplatin; etoposide phosphate

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2015
• First Posted: October 20, 2015
• Study Start: December 8, 2017
• Primary Completion: September 22, 2020
• Study Completion: June 22, 2022
• Last Updated: December 11, 2023

Record last verified: 2023-12

Locations

IT (6); GB (2); FR (10)