Informations générales (source: ClinicalTrials.gov)
A Multicentre Phase II, Open-label, Non-randomized Study Evaluating Platinum-Pemetrexed-Atezolizumab (+/- Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With EGFR Mutations, ALK Rearrangement or ROS1 Fusion Progressing After Targeted Therapies (GFPC 06-2018)
Interventional
Phase 2
Centre Francois Baclesse (Voir sur ClinicalTrials)
septembre 2019
juin 2025
13 août 2024
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CHI DE CRETEIL | Isabelle MONNET | 29/03/2024 01:28:36 | Contacter | ||
| CLCC INSTITUT CURIE | 10/04/2025 13:12:15 | Contact (sur clinicalTrials) | |||
| HOPITAL FOCH | HELENE DOUBRE | 28/04/2025 15:59:52 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| HIA PERCY | BYLICKI Olivier, MD | Contact (sur clinicalTrials) | |||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre François Baclesse - 14076 - Caen - France | GERVAIS Radj, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier - Annecy - France | HOMINAL Stéphane, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Bretagne Atlantique - Vannes - France | Gonzague DE CHABOT, MD | Contact (sur clinicalTrials) | |||
| Centre Paul Strauss - Strasbourg - France | SCHOTT Roland, MD | Contact (sur clinicalTrials) | |||
| CHIC - Créteil - France | MONNET Isabelle, MD | Contact (sur clinicalTrials) | |||
| CHU - Angers - France | JUSTEAU Gregoire, MD | Contact (sur clinicalTrials) | |||
| CHU - Pierre-Bénite - France | COURAUD Sébastien, MD | Contact (sur clinicalTrials) | |||
| CHU - Rennes - France | LENA Hervé, MD | Contact (sur clinicalTrials) | |||
| CHU - Rouen - France | BOTA Suzanna, MD | Contact (sur clinicalTrials) | |||
| CHU-Hôpital MORVAN - Brest - France | DESCOURT Renaud, MD | Contact (sur clinicalTrials) | |||
| HIA R.Picqué - Villenave-d'Ornon - France | PELONI Jean-Michel, MD | Contact (sur clinicalTrials) | |||
| HIA St Anne - Toulon - France | PALEIRON Nicolas, MD | Contact (sur clinicalTrials) | |||
| Hôpital Haut Lévêque,Centre François Magendie - Pessac - France | VEILLON Rémi, MD | Contact (sur clinicalTrials) | |||
| Hôpital Nord - Marseille - France | GREILLER Laurent, PhD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Hospitalier - Villefranche - France | ARPIN Dominique, MD | Contact (sur clinicalTrials) | |||
| CHD Vendée La Roche sur Yon - La Roche sur Yon - France | Acya BIZIEUX, MD | Contact (sur clinicalTrials) | |||
| CHR Orléans - Orléans - France | Hugues MOREL, MD | Contact (sur clinicalTrials) | |||
| CHU - Grenoble - France | MORO-SIBILOT Denis, PhD | Contact (sur clinicalTrials) | |||
| CHU - Lille - France | Alexis CORTOT, MD | Contact (sur clinicalTrials) | |||
| CHU - Toulouse - France | BIGAY GAME Laurence, MD | Contact (sur clinicalTrials) | |||
| CHU Gabriel MONTPIED - Clermont-Ferrand - France | JANICOT Henri, MD | Contact (sur clinicalTrials) | |||
| CHU Lyon Louis Pradel - Bron - France | Sebastien COURAUD, PhD | Contact (sur clinicalTrials) | |||
| CHU Lyon, Croix-Rousse, - Lyon - France | Sebastien COURAUD, PhD | Contact (sur clinicalTrials) | |||
| CHU Réunion St Denis - La Réunion - France | Diane MOREAU, MD | Contact (sur clinicalTrials) | |||
| CHU Réunion St Pierre - La Réunion - France | Eric HUCHOT, MD | Contact (sur clinicalTrials) | |||
| Hopital Foch - Paris - France | DOUBRE Helene, MD | Contact (sur clinicalTrials) | |||
| ICLN, St Priez en Jarez - Saint-Priest-en-Jarez - France | FOURNEL Pierre, PhD | Contact (sur clinicalTrials) | |||
Critères
Tous
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:
- Only supratentorial and cerebellar metastases allowed (i.e., no metastases to
midbrain, pons, medulla, or spinal cord)
- No ongoing requirement for corticosteroids as therapy for CNS disease
- No stereotactic radiation within 7 days or whole-brain radiation within 14 days
prior to inclusion
- 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
- 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:
- Only supratentorial and cerebellar metastases allowed (i.e., no metastases to
midbrain, pons, medulla, or spinal cord)
- No ongoing requirement for corticosteroids as therapy for CNS disease
- No stereotactic radiation within 7 days or whole-brain radiation within 14 days
prior to inclusion
- 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
Cancer-specific exclusions
- Active CNS metastases as determined by CT or magnetic resonance imaging (MRI)
evaluation during screening and prior radiographic assessments
- Spinal cord compression not definitively treated with surgery and/or radiation or
previously diagnosed and treated spinal cord compression without evidence that
disease has been clinically stable for > or = 2 weeks prior to C1
- Leptomeningeal disease (Presence of cancer cells in cerebral CSF or MRI with
leptomeningeal lesion strongly suspected of leptomeningeal disease )
- Uncontrolled tumour-related pain
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently); Patients with indwelling
catheters (e.g., PleurX) are allowed.
- Uncontrolled or symptomatic hypercalcemia (>1.5 mmol/L ionized calcium or calcium
>12 mg/dL or corrected serum calcium > ULN)
- Malignancies other than NSCLC within 5 years prior to C1, with the exception of
those with a negligible risk of metastasis or death treated with expected curative
outcome (such as adequately treated carcinoma in situ of the cervix, basal or
squamous-cell skin cancer, localized prostate cancer treated surgically with
curative intent, ductal carcinoma in situ treated surgically with curative intent)
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
- Patients with a history of autoimmune-related hypothyroidism on a stable dose
of thyroid replacement hormone are eligible for this study.
- Patients with controlled Type 1 diabetes mellitus on a stable dose of insulin
regimen are eligible for this study
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only are permitted provided that they meet the
following conditions:
- Rash must cover less than 10 percent of body surface area (BSA).
- No acute exacerbations of underlying condition within the previous 12 months
(not requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate,
retinoids, biologic agents, oral calcineurin inhibitors, high-potency or oral
steroids)
- 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
- Patients who have had prior anti-cytotoxic T-lymphocyte associated antigen 4
(CTLA-4) treatment may be enrolled, provided the following requirements are
met:
- Last dose of anti-CTLA-4 at least 6 weeks prior to C1
- No history of severe immune-related adverse effects from anti-CTLA-4 (NCI CTCAE
Grade 3/4)
- 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
- History of allergic reactions to cisplatin, carboplatin, or other
platinum-containing compounds
- Patients with hearing impairment (cisplatin)
- Grade > or = 2 peripheral neuropathy as defined by NCI CTCAE v5.0 (cisplatin)
- CRCL < 60 mL/min for cisplatin or < 45 mL/min for carboplatin using the
Cockcroft-Gault Method
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:
- Aortic aneurysm requiring surgical repair
- Recent arterial thrombosis
- Haemoptysis (>one-half teaspoon of bright red blood per episode (within one
months prior to C1) (grade 2 haemoptysis)
- 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.