Clinical Trials List
Protocol NumberXL184-315
2020-08-01 - 2025-04-07
Phase III
Recruiting4
Terminated4
ICD-10C61
Malignant neoplasm of prostate
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9185
Malignant neoplasm of prostate
A Phase 3, Randomized, Open-Label, Controlled Study of Cabozantinib (XL184) in Combination with Atezolizumab vs Second Novel Hormonal Therapy (NHT) in Subjects with Metastatic Castration-Resistant Prostate Cancer
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Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
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Sponsor
Exelixis, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Jiann-Hui Ou 無
- Kwang-Yu Chang 無
- Kuan-Yu Wu 無
- Che-Yuan Hu 無
- Wen-Pin Su 無
- 戴大堯 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chuan-Shu Chen 無
- Jian-Ri Li 無
- 盧嘉文 無
- 裘坤元 無
- 洪晟鈞 無
- 梅承恩 無
- 熊小澐 無
- Chia-Yen Lin 無
- 蔡世傳 無
- 王樹吉 無
- Shian-Shiang Wang 無
- 林雁婷 無
- Cheng-Che Chen 無
- 張瓈文 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Hong-Cheng Gan 無
- PO-HUNG LIN 無
- Rita cheng 無
- 黃亮鋼 無
- Yung-Chang Lin 無
- 張境夫 無
- 黃文冠 無
- Po-Jung Su 無
- Yuan-Cheng Chu 無
- I-hung Shao 無
- Yung-Chia Kao 無
- 吳俊德 無
- 張鈞弼 無
- See-Tong Pang 無
- Feng-Yuan Liu 無
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Principal Investigator
Co-Principal Investigator
- 林仁泰 無
- 吳東霖 無
- 陳逸軒 無
- Chun-Chieh Wang 無
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Metastatic Castration-Resistant Prostate Cancer
Objectives
To evaluate the efficacy of cabozantinib in combination with atezolizumab versus second NHT (abiraterone or enzalutamide) in subjects with first or second line mCRPC who have previously received one and only one NHT (eg, abiraterone, apalutamide, darolutamide, or enzalutamide) to treat mCSPC, M0 CRPC, or mCRPC, and who have measurable visceral disease or measurable extrapelvic adenopathy.
Test Drug
Cabometyx; Tecentriq; Zytiga; Xtandi; Prednisone
Active Ingredient
Abiraterone Acetate
Atezolizumab
Cabozantinib
Atezolizumab
Cabozantinib
Dosage Form
film-coated tablet
Concentrate for solution for infusion
Film-Coated Tablets
Concentrate for solution for infusion
Film-Coated Tablets
Dosage
20
1200/20
500
1200/20
500
Endpoints
Primary End Point
• Duration of PFS per RECIST 1.1 per BIRC
• Duration of OS
Secondary End Point
• ORR per RECIST 1.1 per BIRC
• Duration of PFS per RECIST 1.1 per BIRC
• Duration of OS
Secondary End Point
• ORR per RECIST 1.1 per BIRC
Inclution Criteria
PRINCIPAL INCLUSION CRITERIA
1. Men with histologically or cytologically confirmed adenocarcinoma of the prostate.
2. Prior treatment with one, and only one, NHT (eg, abiraterone, apalutamide, darolutamide, or enzalutamide) for castration-sensitive locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer, M0 CRPC, or mCRPC.
3. Bilateral orchiectomy or ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist (surgical or medical castration), with serum testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening.
4. Measurable (extrapelvic soft tissue) metastatic disease per Investigator assessment as defined by at least one of the following:
a. Measurable visceral (eg, adrenal, kidney, liver, lung, pancreas, spleen) disease per RECIST 1.1, OR
b. Measurable extrapelvic adenopathy (ie, adenopathy above the aortic bifurcation).
5. Progressive disease at study entry as defined by at least one of the following two criteria:
a. Prostate specific antigen (PSA) progression defined by a minimum of 2 rising PSA values from 3 or 4 consecutive assessments with an interval of at least 7 days between assessments.
6. Age ≥ 18 years old or meeting country definition of adult, whichever is older, on the day of consent.
7. ECOG performance status score of 0 or 1.
8. Recovery to baseline or ≤ Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy in the opinion of the Investigator.
9. Adequate organ and marrow function, based upon all of the following laboratory assessments from samples obtained within 21 days before randomization:
a. Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 × 109/L) without granulocyte colony stimulating factor support within 2 weeks before screening laboratory sample collection.
b. Platelets ≥ 100,000/mm3 (≥ 100 × 109/L) without transfusion within 2 weeks before screening laboratory sample collection.
c. Hemoglobin ≥ 9 g/dL (≥ 90 g/L) without transfusion within 1 week before screening laboratory sample collection.
d. Serum bilirubin ≤ 1.5 × upper limit of normal (ULN)
e. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) both ≤ 3 × ULN. Subjects with known hepatic metastasis may enroll with serum ALT and AST both ≤ 5 × ULN.
f. Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault equation: (140 – age) × weight (kg)/(serum creatinine [mg/dL] × 72).
g. Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.1 mg/mmol) or 24-hour urine protein < 1 g.
h. Negative hepatitis B surface antigen (HBsAg) test
i. Negative hepatitis C virus (HCV) antibody test, or positive HCV antibody test followed by a negative HCV RNA test and no ongoing anti-HCV therapy.
10. Understanding and ability to comply with the protocol requirements, including scheduled visits, treatment plan, laboratory tests, and all other study procedures. Evidence of a signed and dated ICF, indicating that the subject has been informed of all pertinent aspects of the study, prior to any screening assessments except those procedures performed as standard of care within the screening window.
11. Sexually active fertile subjects and their female partners must agree to use highly effective methods of contraception during the course of the study and for 4 months (16 weeks) after the last dose of cabozantinib in the experimental arm (cabozantinib + atezolizumab), 3 weeks after the last dose of abiraterone (control arm), or 3 months (12 weeks) after the last dose of enzalutamide (control arm). A barrier contraceptive method (eg, condom) is also required. In addition, men must agree not to donate sperm during these same periods.
1. Men with histologically or cytologically confirmed adenocarcinoma of the prostate.
2. Prior treatment with one, and only one, NHT (eg, abiraterone, apalutamide, darolutamide, or enzalutamide) for castration-sensitive locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer, M0 CRPC, or mCRPC.
3. Bilateral orchiectomy or ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist (surgical or medical castration), with serum testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening.
4. Measurable (extrapelvic soft tissue) metastatic disease per Investigator assessment as defined by at least one of the following:
a. Measurable visceral (eg, adrenal, kidney, liver, lung, pancreas, spleen) disease per RECIST 1.1, OR
b. Measurable extrapelvic adenopathy (ie, adenopathy above the aortic bifurcation).
5. Progressive disease at study entry as defined by at least one of the following two criteria:
a. Prostate specific antigen (PSA) progression defined by a minimum of 2 rising PSA values from 3 or 4 consecutive assessments with an interval of at least 7 days between assessments.
6. Age ≥ 18 years old or meeting country definition of adult, whichever is older, on the day of consent.
7. ECOG performance status score of 0 or 1.
8. Recovery to baseline or ≤ Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy in the opinion of the Investigator.
9. Adequate organ and marrow function, based upon all of the following laboratory assessments from samples obtained within 21 days before randomization:
a. Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 × 109/L) without granulocyte colony stimulating factor support within 2 weeks before screening laboratory sample collection.
b. Platelets ≥ 100,000/mm3 (≥ 100 × 109/L) without transfusion within 2 weeks before screening laboratory sample collection.
c. Hemoglobin ≥ 9 g/dL (≥ 90 g/L) without transfusion within 1 week before screening laboratory sample collection.
d. Serum bilirubin ≤ 1.5 × upper limit of normal (ULN)
e. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) both ≤ 3 × ULN. Subjects with known hepatic metastasis may enroll with serum ALT and AST both ≤ 5 × ULN.
f. Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault equation: (140 – age) × weight (kg)/(serum creatinine [mg/dL] × 72).
g. Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.1 mg/mmol) or 24-hour urine protein < 1 g.
h. Negative hepatitis B surface antigen (HBsAg) test
i. Negative hepatitis C virus (HCV) antibody test, or positive HCV antibody test followed by a negative HCV RNA test and no ongoing anti-HCV therapy.
10. Understanding and ability to comply with the protocol requirements, including scheduled visits, treatment plan, laboratory tests, and all other study procedures. Evidence of a signed and dated ICF, indicating that the subject has been informed of all pertinent aspects of the study, prior to any screening assessments except those procedures performed as standard of care within the screening window.
11. Sexually active fertile subjects and their female partners must agree to use highly effective methods of contraception during the course of the study and for 4 months (16 weeks) after the last dose of cabozantinib in the experimental arm (cabozantinib + atezolizumab), 3 weeks after the last dose of abiraterone (control arm), or 3 months (12 weeks) after the last dose of enzalutamide (control arm). A barrier contraceptive method (eg, condom) is also required. In addition, men must agree not to donate sperm during these same periods.
Exclusion Criteria
PRINCIPAL EXCLUSION CRITERIA
1. Only evidence of metastasis is adenopathy below the aortic bifurcation, non measurable soft tissue (visceral or adenopathic) disease per RECIST 1.1, or bone-only disease.
2. Any prior nonhormonal therapy initiated for the treatment of mCRPC.
3. Receipt of abiraterone within 1 week; cyproterone within 10 days; or receipt of flutamide, nilutamide, bicalutamide, enzalutamide, or other androgen-receptor inhibitors within 2 weeks before randomization.
4. Radiation therapy within 4 weeks (2 weeks for bone metastases) prior to randomization. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
5. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy, radiosurgery, or major surgery and clinically stable for at least 4 weeks prior to randomization.
6. Symptomatic or impending spinal cord compression or cauda equina syndrome.
7. Concomitant anticoagulation with oral anticoagulants except for those specified in the protocol.
8. Administration of a live, attenuated vaccine within 30 days prior to randomization. The use of inactivated (killed) vaccines for the prevention of infectious disease is permitted.
9. Systemic treatment with, or any condition requiring, either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to randomization. Subjects with brain metastases requiring systemic corticosteroid at any dose are not eligible.
10. Uncontrolled, significant intercurrent or recent illness that may impede interpretation of safety data, including, but not limited to, the following conditions:
a. Cardiovascular and cardiac disorders
b. Neuropsychiatric disorder likely to interfere with ability to give informed consent or comply with protocol requirements.
c. Gastrointestinal (GI) disorders, including those affecting absorption or associated with a high risk of perforation or fistula formation:
i. Tumors invading the GI tract, active peptic ulcer disease, acute pancreatitis, acute obstruction of the pancreatic or biliary duct, appendicitis, cholangitis, cholecystitis, diverticulitis, gastric outlet obstruction, or inflammatory bowel disease
ii. Abdominal fistula, bowel obstruction, GI perforation, or intraabdominal abscess within 6 months before randomization
d. Hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, clinically significant hematuria, hematemesis, coagulopathy, or other history of significant bleeding within 3 months before randomization.
e. Known cavitating pulmonary lesion(s) or known endobronchial disease manifestation.
f. Lesions invading major pulmonary blood vessels.
g. Other clinically significant disorders, such as:
i. Any active, known or suspected autoimmune disease
ii. Any active infection requiring systemic treatment.
iii. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
iv. Active tuberculosis.
v. Known history of COVID-19 unless the subject has demonstrated recovery from the disease at least 30 days prior to randomization.
vi. History of idiopathic pulmonary fibrosis, organizing pneumonia, druginduced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
vii. Serious non-healing wound/ulcer/bone fracture per Investigator judgment.
viii. Clinically significant malabsorption syndrome per Investigator judgment.
ix. Pharmacologically uncompensated, symptomatic hypothyroidism.
x. Moderate to severe hepatic impairment or known cirrhosis.
xi. Requirement for hemodialysis or peritoneal dialysis.
xii. History of solid organ transplantation
11. Major surgery within 4 weeks prior to randomization. Minor surgeries within 10 days prior to randomization. Subjects must have complete wound healing from major surgery or minor surgery before randomization. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
12. Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG) within 21 days before randomization.
13. Inability or unwillingness to swallow tablets or receive IV administration.
14. Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded.
15. Any other active malignancy at time of randomization or diagnosis of another malignancy within 2 years prior to randomization that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, or carcinoma in situ of the breast.
1. Only evidence of metastasis is adenopathy below the aortic bifurcation, non measurable soft tissue (visceral or adenopathic) disease per RECIST 1.1, or bone-only disease.
2. Any prior nonhormonal therapy initiated for the treatment of mCRPC.
3. Receipt of abiraterone within 1 week; cyproterone within 10 days; or receipt of flutamide, nilutamide, bicalutamide, enzalutamide, or other androgen-receptor inhibitors within 2 weeks before randomization.
4. Radiation therapy within 4 weeks (2 weeks for bone metastases) prior to randomization. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
5. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy, radiosurgery, or major surgery and clinically stable for at least 4 weeks prior to randomization.
6. Symptomatic or impending spinal cord compression or cauda equina syndrome.
7. Concomitant anticoagulation with oral anticoagulants except for those specified in the protocol.
8. Administration of a live, attenuated vaccine within 30 days prior to randomization. The use of inactivated (killed) vaccines for the prevention of infectious disease is permitted.
9. Systemic treatment with, or any condition requiring, either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to randomization. Subjects with brain metastases requiring systemic corticosteroid at any dose are not eligible.
10. Uncontrolled, significant intercurrent or recent illness that may impede interpretation of safety data, including, but not limited to, the following conditions:
a. Cardiovascular and cardiac disorders
b. Neuropsychiatric disorder likely to interfere with ability to give informed consent or comply with protocol requirements.
c. Gastrointestinal (GI) disorders, including those affecting absorption or associated with a high risk of perforation or fistula formation:
i. Tumors invading the GI tract, active peptic ulcer disease, acute pancreatitis, acute obstruction of the pancreatic or biliary duct, appendicitis, cholangitis, cholecystitis, diverticulitis, gastric outlet obstruction, or inflammatory bowel disease
ii. Abdominal fistula, bowel obstruction, GI perforation, or intraabdominal abscess within 6 months before randomization
d. Hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, clinically significant hematuria, hematemesis, coagulopathy, or other history of significant bleeding within 3 months before randomization.
e. Known cavitating pulmonary lesion(s) or known endobronchial disease manifestation.
f. Lesions invading major pulmonary blood vessels.
g. Other clinically significant disorders, such as:
i. Any active, known or suspected autoimmune disease
ii. Any active infection requiring systemic treatment.
iii. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
iv. Active tuberculosis.
v. Known history of COVID-19 unless the subject has demonstrated recovery from the disease at least 30 days prior to randomization.
vi. History of idiopathic pulmonary fibrosis, organizing pneumonia, druginduced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
vii. Serious non-healing wound/ulcer/bone fracture per Investigator judgment.
viii. Clinically significant malabsorption syndrome per Investigator judgment.
ix. Pharmacologically uncompensated, symptomatic hypothyroidism.
x. Moderate to severe hepatic impairment or known cirrhosis.
xi. Requirement for hemodialysis or peritoneal dialysis.
xii. History of solid organ transplantation
11. Major surgery within 4 weeks prior to randomization. Minor surgeries within 10 days prior to randomization. Subjects must have complete wound healing from major surgery or minor surgery before randomization. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
12. Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG) within 21 days before randomization.
13. Inability or unwillingness to swallow tablets or receive IV administration.
14. Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded.
15. Any other active malignancy at time of randomization or diagnosis of another malignancy within 2 years prior to randomization that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, or carcinoma in situ of the breast.
The Estimated Number of Participants
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Taiwan
32 participants
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Global
580 participants
