Clinical Trials List
Protocol NumberWO39210
NCT Number(ClinicalTrials.gov Identfier)NCT03024996
2017-02-01 - 2023-02-28
Phase III
Terminated5
ICD-10C64.1
Malignant neoplasm of right kidney, except renal pelvis
ICD-10C64
Malignant neoplasm of kidney, except renal pelvis
A Phase III, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of Atezolizumab (Anti-PD-L1 Antibody) as Adjuvant Therapy in Patients With Renal Cell Carcinoma at High Risk of Developing Metastasis Following Nephrectomy
-
Trial Applicant
-
Sponsor
Hoffmann-La Roche
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Shian-Shiang Wang Division of Urology
- Cheng-Che Chen Division of Urology
- Chia-Yen Lin Division of Urology
- Chuan-Shu Chen Division of Urology
- 熊小澐 Division of Urology
- 盧嘉文 Division of Urology
- Cheng-Kuang Yang Division of Urology
- 洪晟鈞 Division of Urology
- 裘坤元 Division of Urology
- 洪啟峰 Division of Urology
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Tzu-chun Wei Division of Urology
- Hsiao-Jen Chung Division of Urology
- 潘競成 Division of Others
- Yi-Hsiu Huang Division of Urology
- Yen-Hwa Chang Division of Urology
- 沈書慧 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Su-Peng Yeh Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
- Chi-Ping Huang Division of Urology
- Chi-Rei Yang Division of Urology
- 陳冠亨 Division of Urology
- Po-Fan Hsieh Division of Urology
- Hsi-Chin Wu Division of Urology
- Ching-Chan Lin Division of Hematology & Oncology
- Yi-Huei Chang Division of Urology
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
Audit
None
Linkou Chang Gung Medical Foundation
Taiwan National PI
莊正鏗
Co-Principal Investigator
- See-Tong Pang Division of Hematology & Oncology
- Yung-Chia Kao Division of Hematology & Oncology
- 劉忠一 Division of Hematology & Oncology
- Po-Jung Su Division of Hematology & Oncology
- 張英勛 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
2 Completed
Audit
None
Co-Principal Investigator
- - - Division of Urology
- 劉高郎 Division of Radiation Therapy
- YI-KAI CHANG Division of Urology
- Yeong-Shiau Pu Division of Urology
- Ying-Chun Shen Division of Hematology & Oncology
- YU-CHUAN LU Division of Urology
- CHUNG-HSIN CHEN Division of Urology
- JHE-CYUAN GUO Division of Hematology & Oncology
- PO-MING CHOW Division of Urology
- Yu-Chieh Tsai Division of Hematology & Oncology
- 王中傑 Division of Others
The Actual Total Number of Participants Enrolled
0 Completed
Condition/Disease
Renal Cell Carcinoma
Objectives
This is a Phase III, multicenter, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of atezolizumab versus placebo in participants with RCC who are at high risk of disease recurrence following nephrectomy.
Test Drug
Atezolizumab
Active Ingredient
Atezolizumab
Dosage Form
Injection
Dosage
1200mg/20ml
Endpoints
Primary Outcome Measures :
IRF-assessed Disease-Free Survival (DFS) [ Time Frame: From Baseline until first documented recurrence event (up to approximately 88 months) ]
Independent Review Facility (IRF)-assessed DFS is defined as the time from randomization to the earliest death from any cause or the first documented recurrence event assessed by IRF, defined as any of the following: Local recurrence of renal cell carcinoma (RCC), new primary RCC, or distant metastasis of RCC. Tumor assessment will be as per IRF on the basis of radiographic evidence and whenever possible supported/confirmed by biopsy results.
IRF-assessed Disease-Free Survival (DFS) [ Time Frame: From Baseline until first documented recurrence event (up to approximately 88 months) ]
Independent Review Facility (IRF)-assessed DFS is defined as the time from randomization to the earliest death from any cause or the first documented recurrence event assessed by IRF, defined as any of the following: Local recurrence of renal cell carcinoma (RCC), new primary RCC, or distant metastasis of RCC. Tumor assessment will be as per IRF on the basis of radiographic evidence and whenever possible supported/confirmed by biopsy results.
Inclution Criteria
Inclusion Criteria
Patients must meet the following criteria for study entry:
• Signed Informed Consent Form
• Age ≥ 18 years
• ECOG performance status of ≤ 1
• Able to comply with the study protocol, in the investigator’s judgment
• Pathologically confirmed RCC with a component of either clear cell histology or
sarcomatoid histology (sarcomatoid differentiation regardless of the primary
epithelial subtype) that has not been previously treated in the adjuvant or
neoadjuvant setting (See Appendix 10 for further guidelines regarding the
definition of sarcomatoid histology.)
Patients with localized disease with T2 Grade 4, T3a Grade 3−4, T3b/c any
grade, T4 any grade and TxN+ any grade are eligible (see Appendix 3).
Patients with pulmonary (treated with sub-lobar or lobar resection), lymph node,
or soft-tissue metachronous recurrence of disease occurring greater than
12 months following nephrectomy who undergo complete resection (R0;
microscopically margin-negative resection in which no gross of microscopic
disease remains) and have no evidence of disease following metastasectomy
are eligible. Patients with resected CNS and bone metastasis are not eligible.
Patients with synchronous metastases who have undergone complete resection
of residual disease are eligible in the following circumstances: isolated solitary
adrenal metastasis treated with adrenalectomy and lung metastases treatable
with a sub-lobar or lobar resection at the time of nephrectomy. Patients with
resected CNS, bone and other soft-tissue metastasis are not eligible.
Medical Monitor approval is necessary for patients with resected metachronous
and synchronous metastasis.
A TNM/grading high risk classification is not required for patients with
metachronous/synchronous recurrence.
• Radical or partial nephrectomy with lymphadenectomy in select patients
Surgeries may be performed by the open, laparoscopic, or robotic approach.
Nephrectomy should include a lymph node dissection in patients with
suspected nodal metastases on preoperative imaging (e.g., 2 cm) rendering the
patient surgically NED (no evidence of disease). For patients with clinical
venous involvement or whose tumors are clinically > 10 cm, a lymph node
dissection is recommended but not required. The extent of the lymph node
dissection will be at the discretion of the treating surgeon.
For patients with no preoperative evidence of abdominal node involvement and
those not at increased risk of nodal metastases, a lymph node dissection is not
required.
Patients must have a negative surgical margin. Positive surgical margin is
defined as tumor identified at the inked perinephric fat margin surrounding the
nephrectomy specimen (R2), evidence of microscopic disease at the tumor
margin (R1), or evidence of tumor histologically invading or adherent to the
renal vein wall at the margin. Luminal thrombus without venous wall
invasion is not considered a positive margin. The final surgical margin should
be free of disease. Contact the Medical Monitor if clarification is required.
Patients with solitary ipsilateral adrenal metastases who undergo
adrenalectomy at the time of nephrectomy will be eligible.
For patients with evidence of thrombus involving the inferior vena cava and/or
right atrium (i.e., cavoatrial involvement), a thrombectomy should be performed
at the time of the radical nephrectomy.
• Representative formalin-fixed paraffin-embedded (FFPE) resected tumor specimens
in paraffin blocks (blocks preferred) or at least 15 unstained slides, with an
associated pathology report, for central testing and determined to be evaluable for
tumor PD-L1 expression prior to study enrollment
Patients with fewer than 15 unstained slides available at baseline (but no fewer
than 10) may be eligible after discussion with the Medical Monitor.
Tumor tissue should be of good quality based on total and viable tumor content.
Fine-needle aspiration, brushing, cell pellet from pleural effusion, bone
metastases, and lavage samples are not acceptable. For core-needle biopsy
specimens, at least three cores should be submitted for evaluation.
The archival specimen must contain adequate viable tumor tissue to establish
PD-L1 expression status.
Patients who have additional tissue samples from procedures performed at
different times (e.g., nephrectomy and metastasectomy) during the course of
their RCC will be requested (but not required) to also submit these samples for
central testing.
In situations in which multiple specimens were received from different sites or at
different times, the highest score will be used for eligibility.
• Absence of residual disease and absence of metastasis, as confirmed by a negative
baseline computed tomography (CT) of the pelvis, abdomen, and chest no more than
4 weeks prior to randomization (for patients with a contraindication to CT with
contrast, see Section 4.5.5).
Indeterminate pulmonary nodules should be evaluated per guidelines in
Appendix 9. Patients who have stable, pulmonary nodules may be eligible.
Patients with pulmonary nodules 6 mm or less that are clinically not strongly
suspected of being malignant may be eligible. Pulmonary nodules that are
greater than 6 mm require either evidence that the lesion is histologically
benign or demonstration of radiographic stability across imaging tests at least
4 weeks apart.
Other examinations should be performed as clinically indicated.
• Absence of brain metastasis, as confirmed by a negative CT with contrast or MRI
scan of the brain, no more than 4 weeks prior to randomization
Applicable only to patients who are eligible based upon completely resected
metachronous or synchronous lung, adrenal, or soft tissue metastasis
• Full recovery from nephrectomy or metastasectomy within 12 weeks from
randomization following surgery
• Adequate hematologic and end-organ function, defined by the following laboratory
results obtained within 28 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
Patients may be transfused or receive erythropoietic treatment to meet this
criterion.
AST, ALT, and alkaline phosphatase ≤ 2.5 × the upper limit of normal (ULN),
with the following exceptions:
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
This applies only to patients who are not receiving therapeutic
anticoagulation; patients receiving therapeutic anticoagulation should be on
a stable dose.
Calculated creatinine clearance ≥ 20 mL/min (Cockcroft-Gault formula)
• 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 for at least 5 months after the last dose
of study drug
A woman is considered to be of childbearing potential if she is postmenarcheal,
has not reached a postmenopausal state (≥ 12 continuous months of
amenorrhea with no identified cause other than menopause), and has not
undergone surgical sterilization (removal of ovaries and/or uterus).
Examples of contraceptive methods with a failure rate of < 1% per year
include bilateral tubal ligation, male sterilization, established and proper use
of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine
devices, and copper intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical study and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not acceptable methods of
contraception.
Patients must meet the following criteria for study entry:
• Signed Informed Consent Form
• Age ≥ 18 years
• ECOG performance status of ≤ 1
• Able to comply with the study protocol, in the investigator’s judgment
• Pathologically confirmed RCC with a component of either clear cell histology or
sarcomatoid histology (sarcomatoid differentiation regardless of the primary
epithelial subtype) that has not been previously treated in the adjuvant or
neoadjuvant setting (See Appendix 10 for further guidelines regarding the
definition of sarcomatoid histology.)
Patients with localized disease with T2 Grade 4, T3a Grade 3−4, T3b/c any
grade, T4 any grade and TxN+ any grade are eligible (see Appendix 3).
Patients with pulmonary (treated with sub-lobar or lobar resection), lymph node,
or soft-tissue metachronous recurrence of disease occurring greater than
12 months following nephrectomy who undergo complete resection (R0;
microscopically margin-negative resection in which no gross of microscopic
disease remains) and have no evidence of disease following metastasectomy
are eligible. Patients with resected CNS and bone metastasis are not eligible.
Patients with synchronous metastases who have undergone complete resection
of residual disease are eligible in the following circumstances: isolated solitary
adrenal metastasis treated with adrenalectomy and lung metastases treatable
with a sub-lobar or lobar resection at the time of nephrectomy. Patients with
resected CNS, bone and other soft-tissue metastasis are not eligible.
Medical Monitor approval is necessary for patients with resected metachronous
and synchronous metastasis.
A TNM/grading high risk classification is not required for patients with
metachronous/synchronous recurrence.
• Radical or partial nephrectomy with lymphadenectomy in select patients
Surgeries may be performed by the open, laparoscopic, or robotic approach.
Nephrectomy should include a lymph node dissection in patients with
suspected nodal metastases on preoperative imaging (e.g., 2 cm) rendering the
patient surgically NED (no evidence of disease). For patients with clinical
venous involvement or whose tumors are clinically > 10 cm, a lymph node
dissection is recommended but not required. The extent of the lymph node
dissection will be at the discretion of the treating surgeon.
For patients with no preoperative evidence of abdominal node involvement and
those not at increased risk of nodal metastases, a lymph node dissection is not
required.
Patients must have a negative surgical margin. Positive surgical margin is
defined as tumor identified at the inked perinephric fat margin surrounding the
nephrectomy specimen (R2), evidence of microscopic disease at the tumor
margin (R1), or evidence of tumor histologically invading or adherent to the
renal vein wall at the margin. Luminal thrombus without venous wall
invasion is not considered a positive margin. The final surgical margin should
be free of disease. Contact the Medical Monitor if clarification is required.
Patients with solitary ipsilateral adrenal metastases who undergo
adrenalectomy at the time of nephrectomy will be eligible.
For patients with evidence of thrombus involving the inferior vena cava and/or
right atrium (i.e., cavoatrial involvement), a thrombectomy should be performed
at the time of the radical nephrectomy.
• Representative formalin-fixed paraffin-embedded (FFPE) resected tumor specimens
in paraffin blocks (blocks preferred) or at least 15 unstained slides, with an
associated pathology report, for central testing and determined to be evaluable for
tumor PD-L1 expression prior to study enrollment
Patients with fewer than 15 unstained slides available at baseline (but no fewer
than 10) may be eligible after discussion with the Medical Monitor.
Tumor tissue should be of good quality based on total and viable tumor content.
Fine-needle aspiration, brushing, cell pellet from pleural effusion, bone
metastases, and lavage samples are not acceptable. For core-needle biopsy
specimens, at least three cores should be submitted for evaluation.
The archival specimen must contain adequate viable tumor tissue to establish
PD-L1 expression status.
Patients who have additional tissue samples from procedures performed at
different times (e.g., nephrectomy and metastasectomy) during the course of
their RCC will be requested (but not required) to also submit these samples for
central testing.
In situations in which multiple specimens were received from different sites or at
different times, the highest score will be used for eligibility.
• Absence of residual disease and absence of metastasis, as confirmed by a negative
baseline computed tomography (CT) of the pelvis, abdomen, and chest no more than
4 weeks prior to randomization (for patients with a contraindication to CT with
contrast, see Section 4.5.5).
Indeterminate pulmonary nodules should be evaluated per guidelines in
Appendix 9. Patients who have stable, pulmonary nodules may be eligible.
Patients with pulmonary nodules 6 mm or less that are clinically not strongly
suspected of being malignant may be eligible. Pulmonary nodules that are
greater than 6 mm require either evidence that the lesion is histologically
benign or demonstration of radiographic stability across imaging tests at least
4 weeks apart.
Other examinations should be performed as clinically indicated.
• Absence of brain metastasis, as confirmed by a negative CT with contrast or MRI
scan of the brain, no more than 4 weeks prior to randomization
Applicable only to patients who are eligible based upon completely resected
metachronous or synchronous lung, adrenal, or soft tissue metastasis
• Full recovery from nephrectomy or metastasectomy within 12 weeks from
randomization following surgery
• Adequate hematologic and end-organ function, defined by the following laboratory
results obtained within 28 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
Patients may be transfused or receive erythropoietic treatment to meet this
criterion.
AST, ALT, and alkaline phosphatase ≤ 2.5 × the upper limit of normal (ULN),
with the following exceptions:
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
This applies only to patients who are not receiving therapeutic
anticoagulation; patients receiving therapeutic anticoagulation should be on
a stable dose.
Calculated creatinine clearance ≥ 20 mL/min (Cockcroft-Gault formula)
• 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 for at least 5 months after the last dose
of study drug
A woman is considered to be of childbearing potential if she is postmenarcheal,
has not reached a postmenopausal state (≥ 12 continuous months of
amenorrhea with no identified cause other than menopause), and has not
undergone surgical sterilization (removal of ovaries and/or uterus).
Examples of contraceptive methods with a failure rate of < 1% per year
include bilateral tubal ligation, male sterilization, established and proper use
of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine
devices, and copper intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical study and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not acceptable methods of
contraception.
Exclusion Criteria
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:
• Bilateral synchronous tumors with inheritable forms of RCC including
von Hippel-Lindau
• Any approved anti-cancer therapy, including chemotherapy or hormonal therapy,
within 3 weeks prior to initiation of study treatment
Hormone-replacement therapy or oral contraceptives are allowed.
• Treatment with any other investigational agent or participation in another clinical
study with therapeutic intent within 28 days or five half-lives of the investigational
agent, whichever is longer, prior to enrollment
• CNS metastases or leptomeningeal disease
• Malignancies other than RCC within 5 years prior to Cycle 1, Day 1
Patients with low-risk prostate cancer (defined as Stage cT1/T2a, Gleason
score ≤ 6 and PSA ≤ 10 ng/mL) who are treatment-naive or who have been
treated definitively with surgery or radiation and who are currently
undergoing surveillance are eligible.
Patients with malignancies of a negligible risk of metastasis or death (e.g., risk
of metastasis or death <5% at 5 years) are eligible provided they meet all of the
following criteria:
Malignancy treated with expected curative intent (e.g., adequately treated
carcinoma in situ of the cervix, basal or squamous cell skin cancer, or
ductal carcinoma in situ treated surgically with curative intent)
No evidence of recurrence or metastasis by follow-up imaging and any
disease-specific tumor markers
• Life expectancy of < 24 weeks
• Pregnancy or lactation, or intending to become pregnant during the study
Women of childbearing potential must have a negative serum pregnancy test
result within 14 days prior to initiation of study drug.
• Serum albumin < 2.5 g/dL
• 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 any component of the atezolizumab formulation
• 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 (see Appendix 7)
Patients with a history of autoimmune-related hypothyroidism on a stable dose
of thyroid-replacement hormone may be eligible for this study.
Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen
may be eligible for this study.
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only are permitted provided that they meet the
following conditions:
Rash must cover less than 10% of body surface area (BSA)
Disease is well-controlled at baseline and only requiring low potency topical
steroids
No acute exacerbations of underlying condition within the last 12 months
(not requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate,
retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral
steroids)
• Patients with prior allogeneic stem cell or solid organ transplantation
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organizing pneumonia), or evidence of active pneumonitis on screening chest CT
scan
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Significant cardiovascular disease, such as New York Heart Association cardiac
disease (Class III or greater), myocardial infarction within 3 months prior to
randomization, unstable arrhythmias, or unstable angina
• Patients with a known left ventricular ejection fraction (LVEF) < 40%.
Patients with known coronary artery disease, congestive heart failure not
meeting the above criteria, or LVEF < 50% must be on a stable medical regimen
that is optimized in the opinion of the treating physician, in consultation with a
cardiologist if appropriate.
• Positive test for HIV
• Patients with active hepatitis B (defined as having a positive hepatitis B surface
antigen [HBsAg] test at screening) or hepatitis C
Patients with past hepatitis B virus (HBV) infection or resolved HBV infection
(defined as having a negative HBsAg test and a positive antibody to hepatitis B
core antigen [anti-HBc] antibody test) are eligible. A negative HBV DNA test
must be obtained in these patients prior to Cycle 1, Day 1.
Patients who test positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction is negative for HCV RNA.
• Active tuberculosis
• Severe infections within 4 weeks prior to randomization including but not limited to
hospitalization for complications of infection, bacteremia, or severe pneumonia
• Receipt of therapeutic oral or IV antibiotics within 2 weeks prior to randomization
Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
infection or chronic obstructive pulmonary disease or for dental extraction) are
eligible.
• Major surgical procedure within 4 weeks prior to randomization or anticipation of
need for a major surgical procedure during the course of the study other than for
diagnosis.
• Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
Influenza vaccination should be given during influenza season only
(approximately October through May in the Northern Hemisphere and
approximately April through September in the Southern Hemisphere).
Patients must agree not to receive live, attenuated influenza vaccine within
28 days prior to randomization, during treatment, or within 5 months after the
last dose of study drug.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or that may affect the
interpretation of the results or render the patient at high risk from treatment
complications
• Prior treatment with CD137 agonists, anti-CTLA-4, anti-PD−1, or anti−PD-L1
therapeutic antibody or pathway-targeting agents
• Treatment with systemic immunostimulatory agents (including but not limited to
interferons or interleukin-2) within 6 weeks or five half-lives of the drug, whichever is
shorter, prior to randomization
• Treatment with systemic immunosuppressive medications (including but not limited
to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti−tumor necrosis factor agents) within 2 weeks prior to randomization or
anticipated need for systemic immunosuppressive medications during the study
Patients who have received acute, low-dose (≤ 10 mg/day oral prednisone or
equivalent), systemic immunosuppressant medications (e.g., 48 hours of
corticosteroids for a contrast allergy) are eligible for the study.
The use of corticosteroids (≤ 10 mg oral prednisone or equivalent), physiologic
replacement doses of glucocorticoids, and mineralocorticoids (e.g.,
fludrocortisone for non-autoimmune adrenal insufficiency) is allowed.
Patients who meet any of the following criteria will be excluded from study entry:
• Bilateral synchronous tumors with inheritable forms of RCC including
von Hippel-Lindau
• Any approved anti-cancer therapy, including chemotherapy or hormonal therapy,
within 3 weeks prior to initiation of study treatment
Hormone-replacement therapy or oral contraceptives are allowed.
• Treatment with any other investigational agent or participation in another clinical
study with therapeutic intent within 28 days or five half-lives of the investigational
agent, whichever is longer, prior to enrollment
• CNS metastases or leptomeningeal disease
• Malignancies other than RCC within 5 years prior to Cycle 1, Day 1
Patients with low-risk prostate cancer (defined as Stage cT1/T2a, Gleason
score ≤ 6 and PSA ≤ 10 ng/mL) who are treatment-naive or who have been
treated definitively with surgery or radiation and who are currently
undergoing surveillance are eligible.
Patients with malignancies of a negligible risk of metastasis or death (e.g., risk
of metastasis or death <5% at 5 years) are eligible provided they meet all of the
following criteria:
Malignancy treated with expected curative intent (e.g., adequately treated
carcinoma in situ of the cervix, basal or squamous cell skin cancer, or
ductal carcinoma in situ treated surgically with curative intent)
No evidence of recurrence or metastasis by follow-up imaging and any
disease-specific tumor markers
• Life expectancy of < 24 weeks
• Pregnancy or lactation, or intending to become pregnant during the study
Women of childbearing potential must have a negative serum pregnancy test
result within 14 days prior to initiation of study drug.
• Serum albumin < 2.5 g/dL
• 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 any component of the atezolizumab formulation
• 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 (see Appendix 7)
Patients with a history of autoimmune-related hypothyroidism on a stable dose
of thyroid-replacement hormone may be eligible for this study.
Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen
may be eligible for this study.
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only are permitted provided that they meet the
following conditions:
Rash must cover less than 10% of body surface area (BSA)
Disease is well-controlled at baseline and only requiring low potency topical
steroids
No acute exacerbations of underlying condition within the last 12 months
(not requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate,
retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral
steroids)
• Patients with prior allogeneic stem cell or solid organ transplantation
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organizing pneumonia), or evidence of active pneumonitis on screening chest CT
scan
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Significant cardiovascular disease, such as New York Heart Association cardiac
disease (Class III or greater), myocardial infarction within 3 months prior to
randomization, unstable arrhythmias, or unstable angina
• Patients with a known left ventricular ejection fraction (LVEF) < 40%.
Patients with known coronary artery disease, congestive heart failure not
meeting the above criteria, or LVEF < 50% must be on a stable medical regimen
that is optimized in the opinion of the treating physician, in consultation with a
cardiologist if appropriate.
• Positive test for HIV
• Patients with active hepatitis B (defined as having a positive hepatitis B surface
antigen [HBsAg] test at screening) or hepatitis C
Patients with past hepatitis B virus (HBV) infection or resolved HBV infection
(defined as having a negative HBsAg test and a positive antibody to hepatitis B
core antigen [anti-HBc] antibody test) are eligible. A negative HBV DNA test
must be obtained in these patients prior to Cycle 1, Day 1.
Patients who test positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction is negative for HCV RNA.
• Active tuberculosis
• Severe infections within 4 weeks prior to randomization including but not limited to
hospitalization for complications of infection, bacteremia, or severe pneumonia
• Receipt of therapeutic oral or IV antibiotics within 2 weeks prior to randomization
Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
infection or chronic obstructive pulmonary disease or for dental extraction) are
eligible.
• Major surgical procedure within 4 weeks prior to randomization or anticipation of
need for a major surgical procedure during the course of the study other than for
diagnosis.
• Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
Influenza vaccination should be given during influenza season only
(approximately October through May in the Northern Hemisphere and
approximately April through September in the Southern Hemisphere).
Patients must agree not to receive live, attenuated influenza vaccine within
28 days prior to randomization, during treatment, or within 5 months after the
last dose of study drug.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or that may affect the
interpretation of the results or render the patient at high risk from treatment
complications
• Prior treatment with CD137 agonists, anti-CTLA-4, anti-PD−1, or anti−PD-L1
therapeutic antibody or pathway-targeting agents
• Treatment with systemic immunostimulatory agents (including but not limited to
interferons or interleukin-2) within 6 weeks or five half-lives of the drug, whichever is
shorter, prior to randomization
• Treatment with systemic immunosuppressive medications (including but not limited
to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti−tumor necrosis factor agents) within 2 weeks prior to randomization or
anticipated need for systemic immunosuppressive medications during the study
Patients who have received acute, low-dose (≤ 10 mg/day oral prednisone or
equivalent), systemic immunosuppressant medications (e.g., 48 hours of
corticosteroids for a contrast allergy) are eligible for the study.
The use of corticosteroids (≤ 10 mg oral prednisone or equivalent), physiologic
replacement doses of glucocorticoids, and mineralocorticoids (e.g.,
fludrocortisone for non-autoimmune adrenal insufficiency) is allowed.
The Estimated Number of Participants
-
Taiwan
15 participants
-
Global
664 participants
