Atezolizumab in Advanced Non-small Cell Lung Cancer With Rare Histologies (CHANCE Trial)

Non-Small Cell Lung Cancer Clinical Trial

— CHANCE  

Official title:

Phase II, Open-label Study of Atezolizumab in a Cohort of Pretreated, Advanced Non-small Cell Lung Cancer (NSCLC) Patients With Rare Histological Subtypes (CHANCE Trial).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03976518
• Other study ID #: GOIRC-02-2018
• Status: Completed
• Phase: Phase 2
• Start date: May 7, 2019
• Est. completion date: February 12, 2024

Study information

• Verified date: February 2024
• Source: Gruppo Oncologico Italiano di Ricerca Clinica
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is aimed to explore the antitumor activity and the safety profile of atezolizumab in pretreated advanced NSCLC patients with rare histological subtypes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: February 12, 2024
• Est. primary completion date: February 12, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Locally advanced, relapsed or metastatic non-small cell lung cancer (NSCLC) - stage IIIB/IV according to 7th International Association for the Study of Lung Cancer (IASLC) classification

• Histologically confirmed diagnosis of non-small cell lung cancer (NSCLC) with rare histological subtype, according to World Health Organization (WHO) 2015 classification. Histologic subtype variants to be enrolled into the study include: colloid adenocarcinoma (or adenocarcinoma with colloid features); fetal adenocarcinoma (or adenocarcinoma with fetal features); large cell carcinoma (LCC); sarcomatoid carcinoma (pleomorphic, spindle cell, and/or giant cell carcinoma, carcinosarcoma, pulmonary blastoma); salivary gland-type tumors (mucoepidermoid carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma), other and unclassified carcinomas (lymphoepithelioma-like carcinoma, NUT-nuclear protein in testis-carcinoma)

• Availability of tumor sample (material obtained from core-biopsy or surgical specimen) for central pathology revision is mandatory

• Availability of a formalin-fixed, paraffin-embedded (FFPE) tumor block or 7-10 unstained tumor slides suitable for PD-L1 expression assessment is mandatory. The assessment of PD-L1 expression will be performed by using both SP-142 and SP-263 antibody assays. The collection of tumor sample should be performed before patients are enrolled into the study

• Male and female and = 18 years of age

• Life expectancy = 12 weeks

• Progressive disease after or during at least one previous standard chemotherapy line

• Measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1); clear radiological evidence of disease progression after previous treatment has to be documented

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2

• Patients with treated brain metastases with stable lesions for at least 2 weeks either off steroids or on a stable dose or decreasing dose of steroids (= 10 mg prednisone or equivalent daily) will be enrolled. Radiotherapy must have been completed a minimum of 14 days prior to registration, and patients must have recovered from adverse events (AEs) related to radiotherapy to < grade 1 (except alopecia)

• For Females: must be postmenopausal for at least 1 year before the screening visit, or are surgically sterile or not sexually active. Women of childbearing potential (WOCBP) must use 2 effective methods of contraception with a failure rate of less than 1% per year, during the entire study treatment period and for a period of 5 months after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. WOCBP must have a negative serum pregnancy test during the screening period

• Adequate haematological function defined by white blood cell (WBC) count =2,500/mm3 with absolute neutrophil count (ANC) =1,500/mm3, platelet count - Adequate hepatic function defined by a total bilirubin = 1.5 x the upper limit of normal (ULN) range (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL), serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN (= 5 if liver function test elevations are due to liver metastases)

• Adequate renal function defined by a serum creatinine = 1.5 x ULN or an estimated creatinine clearance of = 30 mL/minute for patients with creatinine levels above institutional limits (if using the Cockcroft-Gault formula)

• Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before registration, and otherwise noted in other inclusion/exclusion criteria

• Recovered (i.e., = Grade 1 toxicity) from effects of prior anticancer therapy, except alopecia

• Ability to comply with protocol requirements

• The patient is able to provide written informed consent. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that the patient may withdraw consent at any time without prejudice to future medical care.

Exclusion Criteria:

• Prior treatment with Atezolizumab or any other immunotherapy agents (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways)

• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation

• Concurrent anticancer treatment, immune therapy, or cytokine therapy, except for erythropoietin

• Major surgery for any reason within 4 weeks (or 2 weeks for minor surgery) from registration and/or if the subject has not fully recovery from the surgery within 4 weeks of registration

• Subjects receiving immunosuppressive agents such as steroids for any reason should be tapered off these drugs before initiation of the trial treatment. Corticosteroid therapy with a dose = 10 mg prednisone or equivalent will be allowed. Note:

1. Subjects receiving bisphosphonates or denosumab are eligible provided treatment was initiated at least 14 days before first dose of trial treatment

2. Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be =10 mg per day of equivalent prednisone

• Persisting toxicity related to prior therapy of grade >1 according to National Cancer Institute - Common Terminology Criteria Adverse Event (NCI-CTCAE) v. 4.03

• Known severe hypersensitivity reactions to chimeric or monoclonal antibodies, fusion proteins (grade =3 NCI-CTCAE v. 4.03)

• Patients with untreated, symptomatic and/or progressive brain metastases, or with carcinomatous meningitis. Subjects with brain metastases are eligible if metastases have been treated and there is no clinical evidence of progression for [lowest minimum is 2 weeks or more] after treatment is complete and within 28 days prior to the first dose of atezolizumab administration. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent)

• History of autoimmune disease, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis. Subjects with diabetes mellitus type I, hypothyroidism only requiring hormone replacement or controlled hyperthyroidism, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of registration will be not eligible. Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses = 10 mg or 10 mg equivalent prednisone per day. Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption) are permitted

• Any medical condition requiring a systemic corticosteroid treatment at doses >10 mg prednisone per day or equivalent or other immunosuppressive therapies

• Other concurrent neoplasms

• Prior organ transplantation, including allogenic stem-cell transplantation

• Any medical condition, within 6 months before receiving the first dose of study drug, considered relevant by Investigator. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed. Patients who present particular clinical conditions or relevant comorbidity may be enrolled into the study upon discussion with the Study Coordinator

• Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)

• Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection

• Infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before the first dose of study drug

• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan

• Active tuberculosis

• Pregnancy or breastfeeding

• Vaccination within 4 weeks of the first dose of atezolizumab and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated flu vaccines)

• Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site personnel

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Atezolizumab
Atezolizumab will be administered on Day 1 every 21 days (+/- 3 days).

Locations

Country	Name	City	State
Italy	UO di Oncologia Medica - Azienda Ospedaliero-Universitaria S. Orsola Malpighi	Bologna
Italy	Dipartimento di Oncologia Medica - Azienda Ospedaliera S.Croce e Carle Cuneo - Ospedale Carle	Cuneo
Italy	S.S. di Oncologia Medica toraco-polmonare - Fondazione IRCCS - Istituto Nazionale Tumori	Milano
Italy	U.O.C Pneumologia ad Indirizzo Oncologico -AORN Ospedali dei Colli Monaldi-Cotugno-CTO	Napoli
Italy	UO Oncologia Polmonare - AOU S. Luigi Gonzaga	Orbassano	Torino
Italy	UOC di Oncologia Medica 2 - IOV Istituto Oncologico Veneto	Padova
Italy	UOC di Oncologia Medica - Azienda Ospedaliero Universitaria di Parma	Parma
Italy	US di Oncologia Medica - A.O. di Perugia	Perugia
Italy	S.C. di Oncologia Medica - IFO - Istituto Regina Elena	Roma
Italy	UOC di Oncologia Medica - Azienda Sanitaria Universitaria Integrata di Udine	Udine

Sponsors (8)

Lead Sponsor	Collaborator
Gruppo Oncologico Italiano di Ricerca Clinica	AOU S. Orsola Malpighi - Clinical Trial Office, AOU S.Orsola Malpighi-Unit of Oncologic Molecular and Transplantations Pathology, Iqvia Pty Ltd, Istituto Toscano Tumori, Roche SpA, Silvano Chiapparoli Logistica SpA, YGHEA, CRO Division of Ecol Studio spa

Country where clinical trial is conducted

Italy, 

References & Publications (29)

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* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Duration of Response (DoR)	Time from documentation of tumor response (CR or PR) to tumor progression assessed by the Investigators according to standard RECIST 1.1 criteria	From the time of documentation of tumor response to the time of disease progression assessed up to 24 months after baseline
Other	Time to Response	Time from the baseline to a documented tumor response (CR or PR) assessed by the Investigators according to standard RECIST criteria v.1.1.	The occurrence of a response will be assessed from baseline up to 24 months
Other	Tumor shrinkage in target lesions	Tumor shrinkage will be determined based on the change in the sum of the longest diameter of target lesions at each time point	Up to 36 months from the treatment start
Other	PD-L1 marker expression on tumor tissue	Archival tumor tissue (FFPE tumor block or 7-10 unstained slides) will be assessed for determination of PD-L1 status on tumor cells by using both SP-142 and SP-263 antibody assays	Up to 48 months from the treatment start
Other	Predictable value of PD-L1 tumor expression on tumor response	Statistical analysis will be performed to evaluate the role of PD-L1 expression on tumor cells as predictive biomarker of tumor response	Up to 48 months from the treatment start
Other	PD-L1 marker expression on Tumor Infiltrating Lymphocytes (TILs)	Archival tumor tissue (FFPE tumor block or 7-10 unstained slides) will be assessed for determination of PD-L1 status on immune cells by using both SP-142 and SP-263 antibody assays	Up to 48 months from the treatment start
Other	Predictable value of PD-L1 TILs expression on tumor response	Statistical analysis will be performed to evaluate the role of PD-L1 expression on immune cells as predictive biomarker of tumor response	Up to 48 months from the treatment start
Other	Correlation between PD-L1 expression both on tumor cells and on immune cells	Correlation analysis will be performed with the aim to evaluate PD-L1 expression on both tumor cells and immune cells	Up to 48 months from the treatment start
Other	Accuracy of antibody assays SP-142 and SP-263	It will be evaluated the accuracy of both antibody assays and statistical analysis will be performed to investigate their predictive value of response	Up to 48 months from the treatment start
Primary	Disease Control Rate (DCR)	Proportion of patients presenting Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) based on the Investigator's assessment according to standard RECIST criteria v.1.1.	From the start of treatment (baseline) to the progression of disease (PD) or trial discontinuation whichever occurs first, assessed up to 24 months.
Secondary	Treatment Safety based on Adverse Events Frequency and Safety	Frequency and Severity of Adverse Events, the latter measured by each Investigator according to NCI Common Terminology Criteria for Adverse Events, version 4.03	From the treatment start to 90 days after the administration of the last treatment dose. The outcome is assessed up to a maximum of 27 months.
Secondary	Objective Response Rate (ORR)	Proportion of patients presenting Complete Response (CR) or Partial Response (PR) based on Investigator's assessment according to standard RECIST criteria v.1.1.	From the start of treatment (baseline) to the progression or stability of disease assessed up to 24 months.
Secondary	Overall Survival (OS)	Time from enrollment until death from any cause	From the date of enrollment to the date of death from any cause. The survival follow-up will continue until 6 months after the last subject receives the last dose of atezolizumab
Secondary	Time To Progression (Time To Progression)	Time from enrollment until objective tumor progression assessed by the Investigators according to standard RECIST criteria v.1.1.	From the date of enrollment to the date of objective tumor progression assessed up to 24 months.
Secondary	Progression Free Survival (PFS)	Time from enrollment until objective tumor progression or death from any cause or the last date the patient was known-to be progression free or alive	From the date of enrollment to the date of objective disease progression or death assessed up to 24 months.

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