| Eligibility |
Inclusion Criteria:
1. Histologically confirmed small-cell lung cancer.
2. 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).
3. Targetable tumor lesions according to RECIST 1.1. Tumor involvement encompassed into a
radiotherapy field is eligible as target pending that progression is documented.
4. Tumor sample sent to IFCT for PD-L1 immunohistochemistry
5. Previous platinum - etoposide treatment for at least 2 cycles.
6. 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.
7. Age over 18 years.
8. Weight loss = 10% during the last three months.
9. 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.
10. Performance Status 0-2
11. Creatinine clearance > 40 mL/min.
12. Neutrophils = 2,000 µL-1 and platelets = 100,000 µL-1.
13. Bilirubin = 1.5 x normal.
14. Transaminases, alkaline phosphatases = 2.5 x ULN except in case of liver metastases (5
x ULN).
15. Electrocardiogram without sign of progressive coronaropathy.
16. No approved or investigational anti-cancer therapy concurrently or in the 5 years
prior to start of study drug except the first line of treatment of the SCLC, including
tumor embolization, chemotherapy, radiation therapy, immunotherapy, hormone therapy,
biologic therapy, or anti angiogenic therapy (e.g., inhibitors of VEGF or VEGFR
(Vascular Endothelial Growth Factor Receptor).
17. Signed informed consent
18. A female is eligible to enter and participate in this study if she is of:
Non-childbearing potential (i.e., physiologically incapable of becoming pregnant),
including any female who has undergone:
- Hysterectomy.
- Bilateral oophorectomy (ovariectomy).
- Bilateral tubal ligation.
- Or who is post-menopausal:
- Patients not using hormone replacement therapy (HRT) must have experienced total
cessation of menses for =1 year and be greater than 45 years in age, OR, in
questionable cases, have a follicle stimulating hormone value >40 mIU/mL and an
estradiol value <40 pg/mL (<140 pmol/L).
- Subject using HRT must have experienced total cessation of menses for = 1 year and be
greater than 45 years of age OR have had documented evidence of menopause based on FSH
(Follicle Stimulating Hormone) and estradiol concentrations prior to initiation of HRT
(Hormone Replacement Therapy).
Childbearing potential, including any female who has had a negative serum pregnancy test
within 1 week prior to the first dose of study treatment, preferably as close to the first
dose as possible, and agrees to use adequate contraception. Contraceptive methods
acceptable to the IFCT, when used consistently and in accordance with both the product
label and the instructions of the physician, are as follow:
- An intrauterine device with a documented failure rate of less than 1% per year.
- Male partner sterilization (vasectomy with documentation of azoospermia) prior to the
female subject's entry and is the sole sexual partner for that female.
- Complete abstinence from sexual intercourse for 14 days before exposure to
investigational product, through the dosing period, and for at least 21 days after the
last dose of investigational product.
- Double-barrier contraception: condom and an occlusive cap (diaphragm or cervical/vault
caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)
- Oral contraceptive, either combined or progestogen alone
- Injectable progestogen
- Implant of levonorgestrel
- Estrogenic vaginal ring
- Percutaneous contraceptive patches The contraceptive methods must be used during all
the time of the treatment and must be maintained during 5 months after the end of the
treatment in the Atezolizumab arm and 30 days for women, 90 days for men, after the
end of the treatment in the chemotherapy arm.
Female patients who are lactating should discontinue nursing prior to the first dose of
study drug and should refrain from nursing throughout the treatment period and for 15 days
following the last dose of study drug.
A male with a female partner of childbearing potential is eligible to enter and participate
in the study if he uses a barrier method of contraception or abstinence during the study.
Exclusion Criteria:
1. Non-small cell lung cancer or mixed small-cell lung cancer - non small cell cancer.
2. Prior immunotherapy
3. Last dose of the previous treatment received less than 21 days before randomization
(washout period).
4. Corticosteroid with a daily dose over 10 mg prednisolone or equivalent for more than
10 days during the previous month.
5. Unstable angina or uncontrolled cardiac disease.
6. Progressive infection (suggested by a fever associated with hyperleukocytosis,
increase procalcitonin, and increase of C reactive protein without link with a
paraneoplastic syndrome).
7. Patient not able to follow the therapeutic program.
8. Natremia < 125 mmol/L except in case of corrective treatment before the beginning of
the therapy.
9. Hypercalcemia despite corrective treatment (corrected calcemia = Ca++ (mmol) +
[(40-alb (g)) x 0.025].
10. Psychic or mental disease that do not allow the patient to give informed consent.
11. Pregnant or lactating female.
12. 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.
13. 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.
14. 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
15. 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.
16. Presence of any concurrent disease or condition that would make the subject
inappropriate for study participation including any unresolved or unstable, serious
toxicity from prior administration of another investigational drug or any serious
medical disorder that would interfere with the subject's safety, obtaining informed
consent, or compliance with all study related procedures.
17. Administration of a live attenuated vaccine during the four weeks preceding the day 1
of cycle 1, or administration of a vaccine of this type scheduled during the study. An
influenza vaccine should be administered during the influenza season (approximately
from October to March). Patients should not receive a live attenuated influenza
vaccine during the four weeks preceding the day 1 of cycle 1, and shall not receive a
vaccine of this type during the study.
18. History of human immunodeficiency virus infection or chronic hepatitis B or C.
19. Presence of active or uncontrolled infection.
20. Psoriasis patients
21. History of any one or more of the following cardiovascular conditions within the past
6 months:
- Coronary/peripheral artery bypass graft, cardiac angioplasty or stenting.
- Myocardial infarction.
- Severe/unstable angina pectoris.
- Symptomatic peripheral vascular disease, pulmonary embolism or untreated deep
venous thrombosis (DVT), cerebrovascular accident or transient ischemic attack.
- Note: Subject with recent DVT who have been treated with therapeutic
anti-coagulating agents for at least 6 weeks are eligible
- Class III or IV congestive heart failure, as defined by the New York Heart
Association.
22. Concurrent treatment with an investigational agent or participation in another
clinical trial.
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