Platinum-based Chemotherapy With Atezolizumab and Niraparib in Patients With Recurrent Ovarian Cancer
- Conditions
- Recurrent Ovarian Carcinoma
- Interventions
- Registration Number
- NCT03598270
- Lead Sponsor
- Grupo Español de Investigación en Cáncer de Ovario
- Brief Summary
Atezolizumab in this study is expected to have a positive benefit-risk profile for the treatment of patients with platinum-sensitive relapse of ovarian cancer. Of interest, atezolizumab is being investigated also in combination with platinum-based doublet chemotherapy in second line (2L)/ third line (3L) platinum-sensitive recurrent ovarian cancer patients in ATALANTE (NCT02891824), which also includes bevacizumab in the combination. The study is proceeding as expected after \>100 patients enrolled and under independent Data Monitoring Committee (IDMC) supervision.
Platinum-containing therapy is considered the treatment of choice for patients with platinum-sensitive relapse. However the duration of response and the prolongation of the progression free interval with chemotherapy are usually brief, among other because these chemotherapy regimens cannot be continued until progression as they are associated with neurological, renal and hematological toxicity and cannot generally be tolerated for more than about 6 to 9 cycles.
Niraparib received FDA approval in March 2017 as maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. Recently, the European Medicines Agency (EMA) has also approved niraparib as maintenance monotherapy. Despite the progress brought about by niraparib, there is a need for a more effective treatment to extend the progression free interval in this patient population. The combination with immune checkpoint inhibitors such as anti-death protein 1 (anti-PD1) or anti-death protein ligand 1 (anti-PD-L1) has a compelling rationale to this aim, especially under the light of the emerging clinical data of this combination.
The use of atezolizumab concurrent to platinum-containing chemotherapy followed by niraparib as maintenance therapy after completion of chemotherapy, as per normal clinical practice, may provide further benefit to patients in terms of prolonging the progression free interval and increasing the interval between lines of chemotherapy, hence delaying further hospitalization and the cumulative toxicities associated with chemotherapy. Additionally, preliminary studies with atezolizumab suggest an acceptable tolerability profile for long term clinical use in recurrent ovarian cancer patients and other indications.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 414
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Patients ≥ 18 years old
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Life expectancy ≥3 months
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Signed informed consent and ability to comply with treatment and follow-up
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Histologically confirmed diagnosis (cytology alone excluded) of high- grade serous or endometrioid ovarian, primary peritoneal or tubal carcinoma.
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Breast Cancer (BRCA) mutational status is known (germline or somatic)
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Relapsed disease more than 6 months after the last platinum dose
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No more than 2 prior lines of chemotherapy are allowed, and the last one must contain a platinum-based regimen
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At least one measurable lesion to assess response by RECIST v1.1 criteria.
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Mandatory de novo tumor biopsy (collected within 3 months prior to randomization) sent to HistoGene X as a formalin-fixed, paraffin-embedded (FFPE) sample for PD-L1 status determination for randomization. The inclusion of patients with non informative tissue PD-L1 status will be capped to 10% of the whole study population:
- If the mandatory de novo biopsy is technically not possible or failed to produce enough representative tumor tissue, an FFPE sample from archival tissue may be acceptable after approval of the sponsor.
- Bone metastases, fine needle aspiration, brushing, cCell pellet from pleural effusion, or ascites or lavage are not acceptable.
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Two additional tumour samples are needed: Archival tumor sample must be available for exploratory PD-L1 testing in archival tissue and archival or "de novo" tissue sample for biomarkers must also be available.
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Performance status determined by Eastern Cooperative Oncology Group (ECOG) score of 0-1
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Normal organ and bone marrow function:
- Haemoglobin ≥10.0 g/dL
- Absolute neutrophil count (ANC) ≥1.5 x 109/L
- Lymphocyte count ≥0.5 × 109/L
- Platelet count ≥100 x 109/L
- Total bilirubin ≤1.5 x institutional upper limit of normal (ULN)
- Serum albumin ≥2.5 g/dL
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5 x ULN, unless liver metastases are present in which case they must be ≤5 x ULN
- Serum creatinine ≤1.5 x institutional ULN or calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation
- Patients not receiving anticoagulant medication must have an International Normalized Ratio (INR) ≤1.5 and an Activated ProThrombin Time (aPTT) ≤1.5 x ULN.
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Negative Test Results for Hepatitis.
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Toxicities related to previous treatments must be recovered to < grade 2
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Female participants must be postmenopausal or surgically sterile or otherwise have a negative serum pregnancy test within 7 days of the first study treatment and agree to abstain from heterosexual intercourse or use single or combined contraceptive methods.
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Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
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Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment.
- Non-epithelial tumor of the ovary, the fallopian tube or the peritoneum.
- Ovarian tumors of low malignant potential or low grade
- Other malignancy within the last 5 years except curatively treated non-melanoma skin cancer, in situ cancer of the cervix and ductal carcinoma in situ (DCIS)
- Major surgery within 4 weeks of starting study treatment or patients who have not completely recovered (Grade ≥ 2) from the effects of any major surgery at randomization
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1, Cycle 1
- Administration of other chemotherapy drugs, anticancer therapy or anti-neoplastic hormonal therapy, or treatment with other investigational agents or devices within 28 days prior to randomization, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, or anticipation to do it during the trial treatment period (non-investigational hormonal replacement therapy is permitted)
- Palliative radiotherapy (e.g., for pain or bleeding) within 6 weeks prior to randomization or patients who have not completely recovered (Grade ≥ 2) from the effects of previous radiotherapy
- Current or recent (within 10 days prior to randomization) chronic use of aspirin (>325 mg/day) or clopidogrel (>75 mg/day)
- Clinically significant (e.g. active) cardiovascular disease
- Resting ECG with corrected QT interval (QTc) >470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
- Left ventricular ejection fraction defined by multigated acquisition/echocardiogram (MUGA/ECHO) below the institutional lower limit of normal
- History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression
- History or evidence upon neurological examination of central nervous system (CNS) disorders (e.g. uncontrolled epileptic seizures) unless adequately treated with standard medical therapy
- Current, clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease
- Uncontrolled tumor-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 hypercalcemia (>1.5 mmol/L ionized calcium or calcium >12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
- Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications
- Pregnant or lactating women
- Simultaneously receiving therapy in any interventional clinical trial
- Prior treatment with CD137 agonists or immune checkpoint stimulating or blockade therapies, such as anti-PD1, anti-PDL1 or anti-CTLA4 therapeutic antibodies
- Treatment with systemic immunostimulatory agents (including but not limited to interferon-alpha (IFN-α) and interleukin-2 (IL-2) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1
- Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (TNF) agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial
- 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 anti-phospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis
- Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV)
- Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
- Active tuberculosis
- Administration of a live, attenuated vaccine (including against influenza) within 4 weeks prior to Cycle 1, Day 1 or anticipation that it will be administered at any time during the treatment period of the study or within 5 months after the final dose of atezolizumab.
- 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 to any component of the atezolizumab formulation or allergy to any of the other drugs included in the protocol or their solvents (including to Cremophor®)
- Patient has received prior treatment with a poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitor in the recurrent setting or has participated in a study where any treatment arm included administration of a PARP inhibitor in the recurrent setting, unless the patient is unblinded and there is evidence of not having received a PARP inhibitor. Patients that received PARP inhibitor as front line are eligible for the study. The duration of exposure to PARPi following front line therapy needs to be ≥18 months for BRCA mutated patients and ≥ 12 months for BRCA wild type patients.
- Patient has had any known ≥Grade 3 hematological toxicity anemia, neutropenia or thrombocytopenia due to prior cancer chemotherapy that persisted >4 weeks and was related to the most recent treatment
- Patient has any known history or current diagnosis of Myelodysplasic syndrome (MDS) or Anaplastic Myeloid Leukemia (AML)
- Previous allogeneic bone marrow transplant or previous solid organ transplantation
- Patient has a condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results or interfere with the patient's participation for the full duration of the study treatment
- Participant has any known hypersensitivity to niraparib components or excipients
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B (experimental arm) Pegylated liposomal doxorubicin (PLD) Atezolizumab in combination with one of the platinum based regimens below (investigator's choice) followed by maintenance niraparib with atezolizumab: * Carboplatin (AUC = 5, d1) plus paclitaxel and atezolizumab every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. * Carboplatin (AUC = 4, d1) plus gemcitabine and atezolizumab every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. * Carboplatin (AUC = 5, d1) plus pegylated liposomal doxorubicin (PLD) and atezolizumab every 4 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. Arm A (Control Arm) Placebo Placebo of atezolizumab in combination with one of the platinum based regimens below (investigator's choice) followed by maintenance niraparib with placebo: * Carboplatin (AUC = 5, d1) plus paclitaxel and placebo every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks * Carboplatin (AUC = 4, d1) plus gemcitabine and placebo every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks. * Carboplatin (AUC = 5, d1) plus pegylated liposomal doxorubicin (PLD) and placebo every 4 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks. Arm A (Control Arm) Pegylated liposomal doxorubicin (PLD) Placebo of atezolizumab in combination with one of the platinum based regimens below (investigator's choice) followed by maintenance niraparib with placebo: * Carboplatin (AUC = 5, d1) plus paclitaxel and placebo every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks * Carboplatin (AUC = 4, d1) plus gemcitabine and placebo every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks. * Carboplatin (AUC = 5, d1) plus pegylated liposomal doxorubicin (PLD) and placebo every 4 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks. Arm A (Control Arm) Carboplatin Placebo of atezolizumab in combination with one of the platinum based regimens below (investigator's choice) followed by maintenance niraparib with placebo: * Carboplatin (AUC = 5, d1) plus paclitaxel and placebo every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks * Carboplatin (AUC = 4, d1) plus gemcitabine and placebo every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks. * Carboplatin (AUC = 5, d1) plus pegylated liposomal doxorubicin (PLD) and placebo every 4 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks. Arm A (Control Arm) Paclitaxel Placebo of atezolizumab in combination with one of the platinum based regimens below (investigator's choice) followed by maintenance niraparib with placebo: * Carboplatin (AUC = 5, d1) plus paclitaxel and placebo every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks * Carboplatin (AUC = 4, d1) plus gemcitabine and placebo every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks. * Carboplatin (AUC = 5, d1) plus pegylated liposomal doxorubicin (PLD) and placebo every 4 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks. Arm A (Control Arm) Niraparib Placebo of atezolizumab in combination with one of the platinum based regimens below (investigator's choice) followed by maintenance niraparib with placebo: * Carboplatin (AUC = 5, d1) plus paclitaxel and placebo every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks * Carboplatin (AUC = 4, d1) plus gemcitabine and placebo every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks. * Carboplatin (AUC = 5, d1) plus pegylated liposomal doxorubicin (PLD) and placebo every 4 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks. Arm A (Control Arm) Gemcitabine Placebo of atezolizumab in combination with one of the platinum based regimens below (investigator's choice) followed by maintenance niraparib with placebo: * Carboplatin (AUC = 5, d1) plus paclitaxel and placebo every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks * Carboplatin (AUC = 4, d1) plus gemcitabine and placebo every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks. * Carboplatin (AUC = 5, d1) plus pegylated liposomal doxorubicin (PLD) and placebo every 4 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks. Arm B (experimental arm) Carboplatin Atezolizumab in combination with one of the platinum based regimens below (investigator's choice) followed by maintenance niraparib with atezolizumab: * Carboplatin (AUC = 5, d1) plus paclitaxel and atezolizumab every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. * Carboplatin (AUC = 4, d1) plus gemcitabine and atezolizumab every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. * Carboplatin (AUC = 5, d1) plus pegylated liposomal doxorubicin (PLD) and atezolizumab every 4 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. Arm B (experimental arm) Paclitaxel Atezolizumab in combination with one of the platinum based regimens below (investigator's choice) followed by maintenance niraparib with atezolizumab: * Carboplatin (AUC = 5, d1) plus paclitaxel and atezolizumab every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. * Carboplatin (AUC = 4, d1) plus gemcitabine and atezolizumab every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. * Carboplatin (AUC = 5, d1) plus pegylated liposomal doxorubicin (PLD) and atezolizumab every 4 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. Arm B (experimental arm) Niraparib Atezolizumab in combination with one of the platinum based regimens below (investigator's choice) followed by maintenance niraparib with atezolizumab: * Carboplatin (AUC = 5, d1) plus paclitaxel and atezolizumab every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. * Carboplatin (AUC = 4, d1) plus gemcitabine and atezolizumab every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. * Carboplatin (AUC = 5, d1) plus pegylated liposomal doxorubicin (PLD) and atezolizumab every 4 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. Arm B (experimental arm) Atezolizumab Atezolizumab in combination with one of the platinum based regimens below (investigator's choice) followed by maintenance niraparib with atezolizumab: * Carboplatin (AUC = 5, d1) plus paclitaxel and atezolizumab every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. * Carboplatin (AUC = 4, d1) plus gemcitabine and atezolizumab every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. * Carboplatin (AUC = 5, d1) plus pegylated liposomal doxorubicin (PLD) and atezolizumab every 4 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. Arm B (experimental arm) Gemcitabine Atezolizumab in combination with one of the platinum based regimens below (investigator's choice) followed by maintenance niraparib with atezolizumab: * Carboplatin (AUC = 5, d1) plus paclitaxel and atezolizumab every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. * Carboplatin (AUC = 4, d1) plus gemcitabine and atezolizumab every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. * Carboplatin (AUC = 5, d1) plus pegylated liposomal doxorubicin (PLD) and atezolizumab every 4 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks.
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) 30 months Period from study entry (day of randomization) until disease progression, death or date of last contact. Progression will be based on tumor assessment made by the investigators according to the RECIST v1.1 criteria.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) and PD-L1 status 60 months Relationship of PFS with PD-L1 expression status
Time to first subsequent therapy or death (TFST) and PD-L1 status 60 months Relationship of TFST with PD-L1 expression status
Overall survival (OS) 60 months The observed length of life from entry into the study (day of randomization) to death due to any cause, or the date of last contact if patient alive.
Time to first subsequent therapy or death (TFST) 60 months Time from the date of randomization in the current study to the start date of the first subsequent anticancer therapy.
Progression-free survival (PFS) from the beginning of the maintenance phase in all patients, in patients in complete or partial response after completing chemotherapy and in patients with stable disease after completing chemotherapy 60 months Period from start of maintenance treatment until disease progression, death or date of last contact assessed by the investigator according to RECIST v1.1 criteria, in all patients receiving maintenance treatment as well as in the subgroup of patients with complete response/partial response (CR/PR) of stable disease (SD) after completing chemotherapy
Overall Survival (OS) and BRCA status. 60 months Relationship of OS with BRCA mutational status
Duration of Response (DOR) and BRCA status. 60 months Relationship of DOR with BRCA mutational status
Time to second subsequent therapy or death (TSST) 60 months Time from the date of randomization in the current study to the start date of the second subsequent anticancer therapy
Time to second progression or death (PFS2) 60 months Time from treatment randomization to the earliest date of assessment of progression on the next anticancer therapy following study treatment or death by any cause.
Patient-reported abdominal symptoms 60 months Clinically-meaningful improvement in patient-reported abdominal pain or bloating, defined as a 10-point decrease from the baseline score on either of the two items of the EORTC quality of life questionnaire-ovarian cancer module (QLQ-OV28) abdominal/GI symptom scale (items 31 and 32)
Incidence of Treatment Adverse Events 60 months Frequency and severity of adverse events as assessed by CTCAE version 5.0 for the regimens administered on this study
Patient-reported outcomes (PROs) of function and health related quality of life (HRQoL) 60 months Clinical improvement, remaining stable, or deterioration in patient-reported function and HRQoL, defined as a 10-point increase, changes within 10 points, and a 10-point decrease, respectively, from the baseline score on each of the functional (physical, role, emotional, and social) and global health status/HRQoL scales of EORTC QLQ-C30
Objective Response Rate (ORR) 60 months Based on investigator assessment by RECIST v1.1 during the chemotherapy phase and during the maintenance phase
Duration of response (DOR) 60 months Based on investigator assessment by RECIST v1.1 during the chemotherapy phase and during the maintenance phase
Progression Free Survival (PFS) and BRCA status. 60 months Relationship of PFS with BRCA mutational status
Time to first subsequent therapy or death (TFST) and BRCA status. 60 months Relationship of TFST with BRCA mutational status
Objective Response Rate (ORR) and BRCA status. 60 months Relationship of ORR with BRCA mutational status
Duration of Response (DOR) and PD-L1 status 60 months Relationship of DOR with PD-L1 expression status
Overall Survival (OS) and PD-L1 status 60 months Relationship of OS with PD-L1 expression status
Objective Response Rate (ORR) and PD-L1 status 60 months Relationship of ORR with PD-L1 expression status
Efficacy of atezolizumab compared to placebo in the PD-L1 negative and PD-L1 positive subgroups 60 months To evaluate the immune response to atezolizumab
Trial Locations
- Locations (71)
Grand Hôpital de Charleroi
🇧🇪Charleroi, Belgium
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
I.R.C.C.S. Istituto Oncologico Veneto
🇮🇹Padova, Italy
Hôpital Cochin
🇫🇷Paris, France
CHU de Liège, site Sart Tilman
🇧🇪Liège, Belgium
ICO - Paul Paupin - ANGERS
🇫🇷Angers, France
Centre François Baclesse
🇫🇷Caen, France
Centre Léon Bérard
🇫🇷Lyon, France
UZ Leuven
🇧🇪Leuven, Belgium
CHU Besançon
🇫🇷Besançon, France
Institut Bergonié
🇫🇷Bordeaux, France
Centre Jean Perrin
🇫🇷Clermont-Ferrand, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Hochtaunus-Kliniken
🇩🇪Bad Homburg, Germany
CHU Ambroise Paré
🇧🇪Mons, Belgium
CHU UCL Namur site St. Elisabeth
🇧🇪Namur, Belgium
Institut Paoli Calmettes
🇫🇷Marseille, France
ICO Centre René Gauducheau
🇫🇷Saint-Herblain, France
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Diakovere Krankenhaus
🇩🇪Hannover, Germany
Hospital de León
🇪🇸León, Spain
H Reina Sofía Cordoba
🇪🇸Cordoba, Spain
Universitätsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
ROMed Klinikum Rosenheim
🇩🇪Rosenheim, Germany
Asst Lecco
🇮🇹Lecco, Italy
Ospedale Mauriziano Umberto I
🇮🇹Torino, Italy
Universitätsfrauenklinik Ulm
🇩🇪Ulm, Germany
Spedali Civili
🇮🇹Brescia, Italy
HELIOS Dr. Horst Schmidt Kliniken Wiesbaden
🇩🇪Wiesbaden, Germany
Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
AO Città della Salute e della Scienza- Ospedale Sant'Anna
🇮🇹Torino, Italy
Complejo Hospitalario Universitario de A Coruña
🇪🇸A Coruña, Spain
Hospital de la Vall d'Hebron
🇪🇸Barcelona, Spain
ICO Badalona
🇪🇸Badalona, Spain
ICO Girona
🇪🇸Girona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
ICO Hospitalet
🇪🇸Hospitalet del Llobregat, Spain
Clinica Universitaria de Navarra
🇪🇸Madrid, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Son Llatzer
🇪🇸Palma De Mallorca, Spain
Hospital Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Hôpital Européen Georges Pompidou
🇫🇷Paris, France
ICM Val d'Aurelle
🇫🇷Montpellier, France
ONCOGARD - Institut de Cancérologie du Gard
🇫🇷Nîmes, France
Groupe Hospitalier Diaconesses-Croix Saint Simon
🇫🇷Paris, France
HPCA Cario
🇫🇷Plérin Cedex, France
Institut Curie - Hopital Claudius Régaud
🇫🇷Saint-Cloud, France
Institut Curie - Hôpital René Huguenin- SAINT CLOUD
🇫🇷Saint-Cloud, France
Hôpital Tenon
🇫🇷Paris, France
Institut de Cancérologie de Lorraine
🇫🇷Vandœuvre-lès-Nancy, France
Gustave Roussy
🇫🇷Villejuif, France
Universitätsklinikum Mannheim
🇩🇪Mannheim, Germany
Mammazentrum Hamburg am Krankenhaus Jerusalem
🇩🇪Hamburg, Germany
Klinikum Kulmbach
🇩🇪Kulmbach, Germany
Klinikum Oldenburg AöR
🇩🇪Oldenburg, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
MVZ Nordhausen
🇩🇪Nordhausen, Germany
H La Fe de Valencia
🇪🇸Valencia, Spain
Hospital Virgen del Rocio
🇪🇸Sevilla, Spain
H. Clínic Barcelona
🇪🇸Barcelona, Spain
H Morales Meseguer
🇪🇸Murcia, Spain
Complejo Hospitalario Regional de Málaga
🇪🇸Málaga, Spain
Kliniken Essen-Mitte
🇩🇪Essen, Germany
Hospital de Sabadell
🇪🇸Sabadell, Barcelona, Spain