Status and phase
Conditions
Treatments
About
The objective of this study is to assess the efficacy of the combination of Platinum (carboplatin or cisplatin), Pemetrexed, Atezolizumab+/- Bevacizumab if eligible, in stage IIIB/IV non-squamous non-small cell lung cancer patients with progression-enhancing mutations following targeted therapies.
Full description
In patients with an EGFR mutation, several phase III studies comparing EGFR tyrosine kinase inhibitors (TKIs) with chemotherapy have shown a benefit of TKI over chemotherapy, with no demonstrated benefit on overall survival. After a first line of treatment with a TKI, most patients progress and are eligible according to the mechanism of progression to a TKI of 3rd generation in case of T790M resistance or chemotherapy. In patients with ALK translocation, crizotinib has been shown to be beneficial in first line compared to a platinum doublet.Despite these major advances, most patients are progressing after targeted treatments and chemotherapy and are facing the problem of anti-PD1 / PDL1 treatment.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Patient older than 18 years
Subject affiliated to an appropriate social security system
Signed informed consent before any trial related activities and according to local guidelines
ECOG performance status of 0 or 1
Histologically or cytologically confirmed, stage IIIB/IV non-squamous NSCLC (per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system, 7th edition).
Patient with a sensitizing mutation in the EGFR gene must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more EGFR TKIs, such as erlotinib, gefitinib, osimertinib or another EGFR TKI appropriate for the treatment of EGFR-mutant NSCLC. Patients with stage IIIB had to be not operable (that means not eligible for radiochemotherapy followed by a maintenance treatment by Durvalumab)
Patient with an ALK fusion oncogene (confirmed in local laboratory) must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more ALK inhibitors (i.e., crizotinib, alectinib, ceritinib) appropriate for the treatment of NSCLC in patients having an ALK fusion oncogene
Patient with a ROS1 fusion oncogene (confirmed in local laboratory) must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more ROS inhibitors (i.e., crizotinib,) appropriate for the treatment of NSCLC in patients having an ROS1 fusion oncogene
No prior chemotherapy treatment for Stage IV non-squamous NSCLC except if less than 3 cycles, with treatment free-interval of at least 1 year from C1 since last chemotherapy
Patient who has received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from C1since the last chemotherapy, radiotherapy, or chemoradiotherapy
Patient with an history of asymptomatic CNS metastases is eligible, provided he meets all of the following criteria:
Measurable disease, as defined by RECIST v1.1
Adequate hematologic and end-organ function, defined by the following laboratory
Adequate method of contraception during the treatment period and at least 5 months after the last dose of atezolizumab or 6 months after the last dose of chemotherapy
Exclusion criteria
Cancer-specific exclusions
General medical exclusions
Women who are pregnant, lactating, or intending to become pregnant during the study
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
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, Sjogren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan; History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
Positive test for HIV. All patients will be tested for HIV prior to C1 into the study; patients who test positive for HIV will be excluded from the study.
Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible only if they are negative for HBV DNA. Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA.
Active tuberculosis
Severe infections within 4 weeks prior to C1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Received therapeutic oral or IV antibiotics within 1 week prior to C1; Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible.
Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to inclusion, unstable arrhythmias, or unstable angina
Major surgical procedure other than for diagnosis within 28 days prior to C1 or anticipation of need for a major surgical procedure during the course of the study
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications
Symptomatic brain metastases;
Patients with illnesses or conditions that interfere with their capacity to understand, follow and/or comply with study procedures
Concurrent participation in any therapeutic clinical trial
Patient deprived of liberty or placed under the authority of a tutor
Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
Exclusion criteria related to medications
Any approved anti-cancer therapy, including hormonal therapy within 7 days prior to C1 of study treatment.
Treatment with any other investigational agent with therapeutic intent within 28 days prior to C1
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Treatment with systemic immunostimulatory agents (including, but not limited to, interferons, interleukin 2) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to C1 ; Prior treatment with cancer vaccines is allowed.
Treatment with systemic immunosuppressive medications (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to C1
Exclusion criteria related to chemotherapy
Exclusion criteria related to Bevacizumab
Medically uncontrolled hypertension (defined as PAS>150 and/or PAD >100 mmHg)
Prior history of hypertensive crisis or hypertensive encephalopathy
Clinically significant cardiovascular disease (within 6 months prior to C1) that is uncontrolled by medication or may interfere with administration of trial treatment:
History of documented haemorrhagic diathesis or coagulopathy
History of abdominal or tracheosphageal fistula or perforation within 6 months prior to C1
Core biopsy or other minor surgical procedure within 7 days before bevacizumab
Clinical signs or gastrointestinal obstruction or requirement for routine parenteral hydration, nutrition or tube feeding
Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
Major surgery within 28 days before C1
Serious, non-healing wound, active ulcer or untreated bone fracture
Proteinuria >1g/24h urine collection
All patient with >2+ protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection and must demonstrate < or = 1g of protein in 24 hours.
Known sensitivity to any component of bevacizumab
Radiation therapy within 21 days before C1 (except Symptomatic lesions amenable to palliative radiotherapy)
Adequate hematologic, liver, and renal function required (including creatinine clearance 45 mL/min at baseline and 45 mL/min before the start of any subsequent cycle using the Cockcroft-Gault Method.
Primary purpose
Allocation
Interventional model
Masking
149 participants in 2 patient groups
Loading...
Central trial contact
BYLICKI Olivier, MD; GRELLARD Jean-Michel, Project manager
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal