Immunotherapy as Second-line in Patient With Small Cell Lung Cancer

NCT03059667 | Completed Phase 2

• 1 other identifier: IFCT-1603
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 18

Brief Summary

Chemotherapy still constitutes the backbone of small-cell lung cancer (SCLC) therapy, particularly in the extensive disease (ED) stage (ED-SCLC). Despite the fact that a substantial complete response rate could be achieved in SCLC patients receiving etoposide - cisplatin doublet, cure remains the exception. Overall survival in patients receiving this combination is 10 months and progression free survival 6.3 months. At time of progression two options are hitherto accepted: reinduction of carboplatin - etoposide doublet or, for patients unfit for reinduction, topotecan single-drug regimen. However, in both clinical cases, median survival hardly achieves 33 weeks. Consistent data using anti - PDL1 (Programmed death-ligand 1) or anti PD1 (programmed cell death 1) antibodies suggest that they are active as single drug regimens in many malignant diseases. Taking into account the rich tumor infiltrating lymphocyte in pathological specimens of SCLC, we can hypothesize that experimental use of ATEZOLIZUMAB (MPDL3280A) in patients is ethical pending that it demonstrates activity in the second line setting.

Conditions

Small Cell Lung Cancer; Small Cell Lung Cancer Limited Stage; Small Cell Lung Cancer Extensive Stage

Keywords

Small Cell Lun cancer; IFCT; immune therapy

Outcome Measures

Primary Outcomes (1)

• Response Rate in the experimental arm

  Maximum changed in target lesions from baseline at 6 weeks

  6 weeks

Secondary Outcomes (6)

• Progression Free Survival

  approximately 36 weeks

• Overall Survival

  approximately 8 months

• Compliance assessed by the number of cycle received by patient

  approximately 36 weeks

• Safety assessed by the maximum grade will be summarized by frequency and proportion of total patients, by system organ class and NCI-CTC, Version 4.0 categories.

  approximately 36 weeks

• Duration of response

  approximately 36 weeks

Other Outcomes (1)

• Response rate according to tissue PD-L1 expression

  At 6 weeks

Study Arms (2)

Arm A : chemotherapy

ACTIVE COMPARATOR

Patients randomly assigned to the control arm will receive either: * topotecan (oral 2.3 mg/m² or IV 1.5 mg/m² day 1-4 recommended) * or re-induction by carboplatin - etoposide chemotherapy.

Drug: Topotecan; Drug: Carboplatin; Drug: Etoposide

Arm B : immune therapy

EXPERIMENTAL

Patients randomly assigned to the experimental arm will receive Anti PDL1 ATEZOLIZUMAB (MPDL3280A) at a fixed dose of 1200 mg IV every three weeks until progression or unacceptable toxicity.

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

Atezolizumab at 1200 mg IV every 3 weeks

Arm B : immune therapy

Topotecan DRUG

oral 2.3 mg/m² or IV 1.5 mg/m² day 1-4 recommended

Arm A : chemotherapy

Carboplatin DRUG

In accordance with the summary of product characteristics.

Arm A : chemotherapy

Etoposide DRUG

In accordance with the summary of product characteristics.

Arm A : chemotherapy

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed small-cell lung cancer.
• Extensive or limited disease according to the criteria of the Veteran's Administration Lung Cancer Group: (disease extended is defined as a disease beyond hemi thorax and supraclavicular lymph node areas. Tumor pleural effusion will be considered as extended disease).
• Targetable tumor lesions according to RECIST 1.1. Tumor involvement encompassed into a radiotherapy field is eligible as target pending that progression is documented.
• Tumor sample sent to IFCT for PD-L1 immunohistochemistry
• Previous platinum - etoposide treatment for at least 2 cycles.
• Demonstrated progression of the disease other than brain metastasis or carcinomatous meningitis.
• For the patient relapsing more than one year after the end of the previous treatment, a new histological confirmation is required before randomization.
• Age over 18 years.
• Weight loss ≤ 10% during the last three months.
• Patients with brain metastases at diagnosis will be eligible pending that they have achieved brain response during the first line therapy (including brain radiotherapy is required) and remain in brain tumor response during the two months prior to randomization.
• Performance Status 0-2
• Creatinine clearance \> 40 mL/min.
• Neutrophils ≥ 2,000 µL-1 and platelets ≥ 100,000 µL-1.
• Bilirubin ≤ 1.5 x normal.
• Transaminases, alkaline phosphatases ≤ 2.5 x ULN except in case of liver metastases (5 x ULN).

You may not qualify if:

• Non-small cell lung cancer or mixed small-cell lung cancer - non small cell cancer.
• Prior immunotherapy
• Last dose of the previous treatment received less than 21 days before randomization (washout period).
• Corticosteroid with a daily dose over 10 mg prednisolone or equivalent for more than 10 days during the previous month.
• Unstable angina or uncontrolled cardiac disease.
• Progressive infection (suggested by a fever associated with hyperleukocytosis, increase procalcitonin, and increase of C reactive protein without link with a paraneoplastic syndrome).
• Patient not able to follow the therapeutic program.
• Natremia \< 125 mmol/L except in case of corrective treatment before the beginning of the therapy.
• Hypercalcemia despite corrective treatment (corrected calcemia = Ca++ (mmol) + \[(40-alb (g)) x 0.025\].
• Psychic or mental disease that do not allow the patient to give informed consent.
• Pregnant or lactating female.
• Systemic immunosuppressive therapy (eg cyclophosphamide, azathioprine, methotrexate, thalidomide and anti-tumor necrosis factor \[TNF\]) during the two weeks preceding the day 1 of cycle 1.
• Auto-immune disease. History of autoimmune disease, including myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, syndrome Guillain-Barré, multiple sclerosis, vasculitis or glomerulonephritis. Patients with a history of hypothyroidism origin autoimmune treated with a stable dose replacement therapy may be eligible for this study. Patients with controlled type 1 diabetes treated with insulin are eligible in this study.
• Idiopathic pulmonary fibrosis history, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced lung disease, idiopathic pulmonary or active signs of pneumonia or interstitial lung infiltrate (any cause) detected on the lung scan selection
• Prior malignancy. Note: Patients who have had another malignancy and were treated more than 5 years ago and have since been considered cured, or patients with a history of basocellular skin carcinoma or in situ carcinoma of the uterine cervix are eligible.

Sponsors & Collaborators

• Intergroupe Francophone de Cancerologie Thoracique: lead

Study Sites (18)

Annemasse - CH

Ambilly, 74100, France

Location

Angers - CHU

Angers, 49000, France

Location

CH

Colmar, France

Location

CHRU Grenoble

Grenoble, France

Location

Centre Hospitalier - Pneumologie

Le Mans, 72000, France

Location

Lorient - CHBS

Lorient, France

Location

Montpellier - CHRU

Montpellier, 34295, France

Location

Mulhouse - CH

Mulhouse, 68000, France

Location

Centre Antoine Lacassagne

Nice, France

Location

AP-HP Hopital Tenon - Pneumologie

Paris, 75020, France

Location

APHP - Paris Bichat

Paris, 75877, France

Location

GH Paris Saint-Joseph

Paris, France

Location

CHG de Pau

Pau, France

Location

HCL - Lyon Sud (Pneumologie)

Pierre-Bénite, 69495, France

Location

Rouen - CHU

Rouen, 76000, France

Location

Centre Hospitalier

Saint-Quentin, France

Location

Toulouse - CHU Larrey

Toulouse, France

Location

CHU Tours - Pneumologie

Tours, France

Location

Related Publications (1)

• Negre E, Coffy A, Langlais A, Daures JP, Lavole A, Quoix E, Molinier O, Greillier L, Audigier-Valette C, Moro-Sibilot D, Westeel V, Morin F, Roch B, Pujol JL. Development and Validation of a Simplified Prognostic Score in SCLC. JTO Clin Res Rep. 2020 Feb 12;1(1):100016. doi: 10.1016/j.jtocrr.2020.100016. eCollection 2020 Mar.

  PMID: 34589918 DERIVED

Related Links

• IFCT website

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

atezolizumab; Topotecan; Carboplatin; Etoposide

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)

Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Jean-Louis PUJOL, MD PhD

  CHU de Montpellier

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 14, 2017
• First Posted: February 23, 2017
• Study Start: March 13, 2017
• Primary Completion: September 10, 2018
• Study Completion: December 1, 2020
• Last Updated: February 10, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (18)