Phase 3 study of immunotherapy combined with growth factor inhibitors compared to conventional sunitinib for advanced kidney cancer

Phase 1

Conditions: advanced kidney cancer
MedDRA version: 20.1Level: LLTClassification code 10023400Term: Kidney cancerSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-004684-20-PL

Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 915

Inclusion Criteria

- Unresectable advanced or metastatic RCC with clear-cell histology
and/or component of sarcomatoid carcinoma
- 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
randomization:
ANC >= 1500 cells/µL (without granulocyte colony stimulating factor
support within 2 weeks prior to Cycle 1, Day 1)
WBC counts >= 2500/µL
Lymphocyte count >= 300/µL
Platelet count >= 100,000/µL (without transfusion within 2 weeks prior
to Cycle 1, Day 1)
Hemoglobin >=9.0 g/dL
AST, ALT, and alkaline phosphatase =< 2.5 × the upper limit of normal
(ULN), with the following exceptions:
Patients with documented liver metastases:
AST and ALT =<5 × ULN
Patients with documented liver or bone metastases: alkaline
phosphatase =< 5 × ULN
Serum bilirubin =<1.5 × ULN
Patients with known Gilbert disease who have serum bilirubin level =<3
× ULN may be enrolled.
INR and aPTT =<1.5 × 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)
- Patients with a history of treated asymptomatic central nervous
system (CNS) metastases are eligible, provided they meet all of the
following criteria:
Evaluable or measurable disease outside the CNS
Only supratentorial and cerebellar metastases allowed (i.e., no
metastases to midbrain, pons, medulla or spinal cord)
No history of intracranial or spinal cord hemorrhage
No evidence of significant vasogenic edema
No ongoing requirement for corticosteroids as therapy for CNS disease
No stereotactic radiation within 14 days
No evidence of interim progression between the completion of CNS
directed therapy and the screening radiographic study
Patients with new asymptomatic CNS metastases detected at the
screening scan must receive radiation therapy and/or surgery for CNS
metastases.
Following treatment, these patients may then be eligible without the
need for an additional brain scan prior to enrollment [or randomization],
if all other criteria are met.
- For women of childbearing potential: agreement to remain abstinent
(refrain from heterosexual intercourse) or use contraceptive methods
that result in a failure rate of < 1% per year during the treatment period
and for at least 6 months after the last dose of atezolizumab and
bevacizumab or 30 days after the last dose of sunitinib
- For men: agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive measures that result in a failure rate of
< 1% per year, and agreement to refrain from donating sperm, for at
least 6 months after the last dose of atezolizumab or bevacizumab or 30
days after the last dose of sunitinib

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 581
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 249

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method