advanced kidney cancer MedDRA version: 17.1 Level: LLT Classification code 10023400 Term: Kidney cancer System Organ Class: 100000004864
Conditions
Interventions
Product Code: MPDL3280A-RO5541267
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not Yet defined
Current Sponsor code: RO5541267
Other descriptive name: MPDL3280A
Concentration unit:
Sponsors
Roche Farma S.A en nombre de F. Hoffmann-La Roche LTD
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ?Unresectable advanced or metastatic RCC with clear cell histology and/or sarcomatoid carcinoma (defined below) ?Measurable disease, as defined by RECIST v1.1 ?Karnofsky performance status ?70 ?Adequate hematologic and end organ function, defined by the following laboratory results obtained within 28 calendar days prior to the first study treatment: ANC ? 1500 cells/?L (without granulocyte colony stimulating factor support within 2 weeks prior to Cycle 1, Day 1) WBC counts ? 2500/?l Lymphocyte count ? 300/?l Platelet count ? 100,000/?l (without transfusion within 2 weeks prior to Cycle 1, Day 1) Hemoglobin ? 9.0 g/dL AST, ALT, and alkaline phosphatase ?2.5 x the upper limit of normal (ULN), with the following exceptions: Patients with documented liver metastases: AST and ALT ? 5 x ULN Patients with documented liver or bone metastases: alkaline phosphatase ?5 x ULN Serum bilirubin ?1.5 x ULN Patients with known Gilbert disease who have serum bilirubin level ? 3 x ULN may be enrolled. INR and aPTT ?1.5 x ULN, unless on a stable dose of warfarin Serum albumin > 2.5 g/dL Creatinine clearance ? 30 mL/min (Cockcroft-Gault formula or based on 24 hour urine collection) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 385 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 165
Exclusion criteria
Exclusion criteria: ?No prior treatment with active or experimental systemic agents for treatment of RCC, including treatment in the neoadjuvant or adjuvant setting. Prior treatment with placebo in adjuvant setting is allowed. ?Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening and prior radiographic assessments ?Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated at least 14 days prior to Cycle 1, Day 1. ?Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) ?Uncontrolled hypercalcemia (>1.5 mmol/L ionized calcium or Ca >12 mg/dL or corrected serum calcium greater than the upper limit of normal]) or symptomatic hypercalcemia refractory to bisphosphonate therapy or denosumab ?Pregnant and 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 ?Malignancies other than RCC within 5 years prior to Cycle 1, Day 1, 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 with curative intent, ductal carcinoma in situ of the breast treated surgically with curative intent). Contact the Medical Monitor if there are concerns or if clarification is needed. ?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, vasculitis, or glomerulonephritis (see the protocol for a more comprehensive list of autoimmune diseases) 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 I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study. ?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 ?Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or Patients with active hepatitis C ?Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the efficacy of MPDL3280A+bevacizumab compared with sunitinib as measured by investigator assessed progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).;Secondary Objective: -To evaluate the efficacy of MPDL3280A + bevacizumab versus sunitinib as measured by Independent Review Committee (IRC)?assessed PFS according to RECIST v1.1 -To evaluate the efficacy of MPDL3280A + bevacizumab versus sunitinib as measured by overall survival (OS) -To evaluate the efficacy of MPDL3280A +bevacizumab versus sunitinib as measured by investigator-assessed objective response rate (ORR) (complete partial response rates) per RECIST v1.1;Primary end point(s): Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1);Timepoint(s) of evaluation of this end point: The primary analysis of PFS is projected to occur at 300 PFS events | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ?PFS based on IRC assessment of radiographic progression per RECIST v1.1 ?OS, defined as the time from randomization to death due to any cause ?Time to deterioration in tiredness on the basis of Question 3 on the BFI ?Change from baseline in the following scores: Fatigue interference (Question 4 on BFI) Symptom interference (from MDASI) Diarrhea severity (from the MDASI) Treatment side effects subscale (from the FKSI-19) ?ORR, defined as the proportion of patients with an objective response (either complete response or partial response, confirmation not required) as determined by investigator per RECIST v1.1 ?DOR, defined as the time from the first documented response to documented disease progression as determined by the investigator per RECIST v1.1 or death due to any cause, whichever occurs first ?ORR and DOR based on IRC assessment per RECIST v1.1 ?PFS, ORR, and DOR based on investigator assessment per modified RECIST criteria ?PFS based on investigator assessment per RECIST v1.1 and OS in patients who have detectable PD-L1 expression, which is defined as IC1/2/3;Timepoint(s) of evaluation of this end point: The end of study will occur when the number of deaths required for the final analysis of OS (307 deaths) in the ITT population have been observed | — |
Countries
Australia, Canada, Czech Republic, Denmark, France, Germany, Italy, Korea, Republic of, Mexico, Netherlands, Poland, Romania, Russian Federation, Spain, Taiwan, Turkey
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed