Locally Advanced Cervical Cancer MedDRA version: 20.0 Level: LLT Classification code 10008229 Term: Cervical cancer System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10048683 Term: Advanced cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Atezolizumab
Product Code: RO5541267/F03
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: RO5541267/F03
Concentration un
Sponsors
Gustave Roussy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent (after informing the patient). 2. Age between 18 and 70 years. 3. Histologically confirmed cancer of the uterine cervix: squamous cell carcinoma (SCC), adenocarcinoma, or adenosquamous carcinoma. 4. At least one evaluable lesion according to RECIST v1.1 criteria for the assessment of the principal judgment criteria. 5. International Federation of Gynecology and Obstetrics (FIGO) classification (confirmed by both clinical staging and imaging): (i) stage IB2-IIA tumour with positive pelvic nodal status, as assessed by magnetic resonance imaging (MRI) and/or fluorine-18 fluorodeoxyglucose positron emission tomography (18-FDG PET)/computerised tomography (CT); (ii) stage IIB-IVA tumour, regardless of pelvic lymph node involvement; (iii) stage IVB tumours only if the metastases are limited to the para-aortic lymph nodes. No evidence of metastatic disease outside the para-aortic area by primary staging (including clinical examination, pelvic MRI, 18-FDG PET, +/- laparoscopic para-aortic lymph node staging). 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 7. Adequate haematologic and end-organ function, defined by the following laboratory results obtained within 15 calendar days prior to the first study treatment: a. Absolute neutrophil count (ANC) =1,500/mm3 (=1.5 x 109/L) without granulocyte colony-stimulating factor (G-CSF) support. b. Polymorphonuclear neutrophils (PMN) >2,000/mm3 (>2.0 x 109/L). c. Lymphocyte count =500/mm3 (= 0.5 x 109/L) d. Platelet count = 100,000/mm3 (= 100 x 109/L) without transfusion. e. Haemoglobin = 9.0 g/dL (90 g/L; patients may be transfused to meet this criterion). f. International Normalized Ratio (INR) and activated partial thromboplastin time (aPTT) = 1.5 × upper limit of normal (ULN) for patients not receiving therapeutic anticoagulation. Patients receiving therapeutic anticoagulation should be on a stable dose. g. Creatinine <1.5 ULN or calculated creatinine clearance (CrCL) = 55 mL/min (calculated using the Cockcroft-Gault formula). h. Aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase <2.5 x ULN. i. Serum bilirubin <1.5 x ULN. 8. Proteinuria < 200 mg/dL (2 g/L). 9. Ability to comply with the study protocol. 10. Geographical, social and psychological ability to undergo the follow-up required by the study. 11. Women who are not postmenopausal (= 12 months of non-therapy-induced amenorrhoea) and not surgically sterile: a. Must agree to either use an acceptable contraceptive method* or to remain abstinent** (refrain from heterosexual intercourse) during the treatment period and for at least 5 months after the last dose of atezolizumab in arm B and at least 6 months after the last cisplatine dose in arm A.. * Acceptable contraceptive methods include single or combined contraceptive methods that result in a failure rate of < 1% per year, such as: tubal ligation, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of < 1% per year. Barrier methods must always be supplemented with the use of a spermicide. ** Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation
Exclusion criteria
Exclusion criteria: 1. Histological types of cervical cancer other than those listed in the inclusion criteria, including: a. Stage IB2 and IIA cervical cancer with no regional lymph node metastases (N0). b. Stage IVB cervical cancer with presence of distant metastases other than para-aortic lymph node metastases. 2. Prior surgery for cervical cancer unless cone resection and paraaortic lymphadenectomy. 3. Prior pelvic radiotherapy, other radiotherapy, chemotherapy or immunotherapy. 4. Any malignancy other than the disease under study in the past 5 years excepting skin cancers such as BCC or SCC. 5. Pregnant or lactating women, or intending to become pregnant during the study. 6. Obesity (Body Mass Index [BMI] > 30). 7. History of clinically relevant cardiovascular disease, congestive heart failure (New York Heart Association [NYHA] Class II or greater), or a known left ventricular ejection fraction (LVEF) <50%, symptomatic coronary artery disease, poorly controlled cardiac arrhythmia, or myocardial infarction. 8. Active inflammatory bowel disease, lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome. 9. Serious infection requiring oral or IV antibiotics within 4 weeks prior to randomisation, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia. 10. Treatment with another investigational therapy within 30 days prior to initiation of the study drug. 11. Major surgical procedure within 4 weeks prior to randomisation or anticipation of the need for a major surgical procedure during the study other than for diagnosis. The following are not considered a major surgical procedure and are therefore permitted: (i) placement of central venous access catheter(s) (e.g., port or similar); (ii) surgical lymph node staging with no perioperative complications; (iii) placement of ureteral catheters. 12. History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins. 13. Known hypersensitivity to Chinese hamster ovary (CHO) cell products or any component of the atezolizumab formulation. 14. Any contraindication to the use of Cisplatin 15. 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, meningoencephalitis, or glomerulonephritis (see Appendix 6 for a more comprehensive list of autoimmune diseases) with the following exceptions: patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone, patients with controlled Type 1 diabetes mellitus on a stable insulin regimen, and patients with mild autoimmune skin disorders (such as eczema or atopic dermatitis involving <10% of the skin) may be eligible for this study. 16. History of idiopathic pulmonary fibrosis (IPF, including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or active pneumonitis. 17. Pre-existing hearing impairment. 18. Peripheral neuropathy =grade 2 19. Positive test for human immunodeficiency virus (HIV). 20. Active hepatitis B (positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C (positive hepatitis C virus antibody [HCVAb] tes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to evaluate the clinical benefits of the addition of atezolizumab to standard chemoradiotherapy (CRT) (first given concurrently with CRT, then continued as adjuvant treatment), compared with CRT alone, on investigator-assessed progression-free survival (PFS), as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and clinical progression;Secondary Objective: 1.To evaluate the efficacy of atezolizumab plus standard CRT compared with CRT alone as measured by objective response rates, locoregional control and overall survival (OS). 2.To evaluate the safety of atezolizumab in combination with CRT compared to CRT alone, including the incidence and severity of acute and delayed radiation-induced side effects in the two treatment arms.;Primary end point(s): The primary endpoint is progression free survival (PFS), defined as the time from randomization to the first documented occurrence of disease progression, as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurs first. Data for patients without disease progression or death will be censored at the date of the last follow-up.;Timepoint(s) of evaluation of this end point: The primary endpoint analysis will be performed when 54 primary endpoint events (progression or death) have occurred in the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall survival (OS), defined as the time from randomisation to death due to any cause. - Complete response rate at 8 weeks, defined as the percentage of patients with measurable disease at baseline, who have achieved complete response (CR) after treatment initiation, as determined by the investigator using RECIST v1.1 criteria. - Locoregional control, defined as the cumulative rate of locoregional recurrence or progression with censoring of deaths without locoregional recurrence or progression. - Distant tumour control: defined as the cumulative rate of (distant) metastatic events with censoring of deaths without metastatic progression. In case locoregional recurrence (or progression) and distant progression occur at the same time, the event will be counted as a distant event. - Toxicity, defined as any adverse drug reaction (AE assessed at least possibly related to any study treatment) that occurs within 6 months following brachytherapy (acute toxicity) or more than 6 months following brachytherapy (late toxicity). Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTC-AE v4.03) at each visit. ;Timepoint(s) of evaluation of this end point: see above | — |
Countries
France
Contacts
Public ContactCRA
Gustave Roussy
Outcome results
None listed