Atezolizumab for Metastatic castration-resistant prostate cancer

Inclusion criteria

• {"criterion_text":"- Men with histologically or cytologically confirmed adenocarcinoma of the prostate.\n- Understanding and ability to comply with the protocol requirements, including scheduled visits, treatment plan, laboratory tests, and all otherstudy 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.\n- 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.\n- Subjects must have had a rising PSA or radiographically progressed on their 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, and/or mCRPC.\n- Bilateral orchiectomy or ongoing ADT with a gonadotropin-releasing hormone (GnRH) agonist/antagonist (surgical or medical castration), with serum testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening.\n- 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).\n- 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 most recent consecutive assessments with an interval of at least 7 days between assessments. b. Soft tissue disease progression (PD) in the opinion of the Investigator.\n- Age ≥ 18 years old or meeting country definition of adult, whichever is older, on the day of consent.\n- ECOG performance status score of 0 or 1.\n- 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.\n- 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 x 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."}

Exclusion criteria

• {"criterion_text":"- 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.\n- Uncontrolled, significant intercurrent or recent illness that may impede analysis of safety data, including, but not limited to, the following: a. Cardiovascular and cardiac disorders b. Neuropsychiatric disorder likely to impede with ability to give informed consent or comply with protocol requirements c. GI disorders, including those affecting absorption or linked 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 IBD ii. Abdominal fistula, bowel obstruction, GI perforation, or intraabdominal abscess within 6 months before randomization d. Hemoptysis of > 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 lesions 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 HIV, AIDS-related illness iv. Active tuberculosis v. Known history of COVID-19 unless the subject has shown 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, known cirrhosis xi. Requirement for hemodialysis, peritoneal dialysis xii. History of solid organ transplantation xiii. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) - Patients with indwelling cathethers (e.g. PleurX®) are allowed\n- 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 problems from prior surgery are not eligible.\n- Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per ECG within 21 days before randomization.\n- Inability or refusal to swallow tablets or receive IV administration.\n- 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.\n- 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.\n- Any prior systemic nonhormonal therapy initiated for the treatment of mCRPC.\n- 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.\n- 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.\n- Known brain metastases (symptomatic or non-symptomatic) or cranial epidural disease unless adequately treated with radiotherapy, radiosurgery, or major surgery and clinically stable for at least 4 weeks prior to randomization.\n- Symptomatic or impending spinal cord compression or cauda equina syndrome.\n- Concomitant anticoagulation with oral anticoagulants including, but not limited to, platelet inhibitors (eg, clopidogrel or ticagrelor), warfarin, dabigatran, and betrixaban, except for those specified in the protocol.\n- Administration of a live, attenuated vaccine within 30 days prior to randomization. The use of inactivated vaccines for the prevention of infectious disease is permitted.\n- 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."}

Primary endpoints

• {"endpoint_text":"- Duration of PFS per RECIST 1.1 per BIRC","definition_or_measurement_approach":"Progression-free survival (PFS) assessed per RECIST 1.1 by a Blinded Independent Radiology Committee (BIRC)."}
• {"endpoint_text":"- Duration of OS","definition_or_measurement_approach":"Overall survival (OS) measured as time from randomization to death from any cause."}

Secondary endpoints

• {"endpoint_text":"- ORR per RECIST 1.1 per BIRC","definition_or_measurement_approach":"Objective response rate (ORR) per RECIST 1.1 as assessed by a Blinded Independent Radiology Committee (BIRC)."}

Other endpoints

• {"endpoint_text":"- Subjects will be monitored for radiographic response and progression per RECIST 1.1 and PCWG3.\n- Routine safety assessments will be done regularly.\n- Health-related quality of life assessments will be performed using the EuroQol Health questionnaire EQ-5D-5L and EORTC questionnaire QLQ-C30.\n- Assessment of pain will be self-reported by each subject using an 11-point (from 0 to 10) numeric rating scale (NRS) measuring worst pain in the last week.\n- Symptomatic skeletal events (SSEs) will be continuously assessed.\n- Healthcare resource utilization parameters (hospital admissions, emergency room visits, intensive care unit admissions, length of stay, surgeries, and transfusions) will also be collected.\n- Biomarker, pharmacokinetics and immunogenicity assessments will be performed.\n- Radiographic tumor, PSA, health-related quality of life (HRQOL), and pain assessments are to continue, regardless of whether study treatment is given, reduced, held or discontinued until a criterion for ending radiographic assessments is met.","definition_or_measurement_approach":"Radiographic response/progression per RECIST 1.1 and PCWG3; safety by routine clinical/laboratory assessments; HRQoL via EQ-5D-5L and EORTC QLQ-C30; pain via 11-point NRS; SSEs as recorded continuously; healthcare resource utilization collected from records; biomarker/PK/immunogenicity via laboratory assays; PSA and radiographic follow-up per protocol-specified schedules."}

Portugal

Earliest CTIS Part Ii Submission Date

21-08-2024

Latest Decision Or Authorization Date

28-08-2024

Processing Time Days

7

Number Of Sites

3

Number Of Participants

15

Italy

Earliest CTIS Part Ii Submission Date

21-08-2024

Latest Decision Or Authorization Date

09-10-2024

Processing Time Days

49

Number Of Sites

4

Number Of Participants

26

Poland

Earliest CTIS Part Ii Submission Date

21-08-2024

Latest Decision Or Authorization Date

02-09-2024

Processing Time Days

12

Number Of Sites

3

Number Of Participants

27

Greece

Earliest CTIS Part Ii Submission Date

18-10-2024

Latest Decision Or Authorization Date

13-11-2024

Processing Time Days

26

Number Of Sites

2

Number Of Participants

37

France

Earliest CTIS Part Ii Submission Date

21-08-2024

Latest Decision Or Authorization Date

02-09-2024

Processing Time Days

12

Number Of Sites

6

Number Of Participants

27

Belgium

Earliest CTIS Part Ii Submission Date

21-08-2024

Latest Decision Or Authorization Date

02-09-2024

Processing Time Days

12

Number Of Sites

1

Number Of Participants

4

Czechia

Earliest CTIS Part Ii Submission Date

21-08-2024

Latest Decision Or Authorization Date

30-08-2024

Processing Time Days

9

Number Of Sites

3

Number Of Participants

10

Germany

Earliest CTIS Part Ii Submission Date

21-08-2024

Latest Decision Or Authorization Date

30-08-2024

Processing Time Days

9

Number Of Sites

4

Number Of Participants

14

Spain

Earliest CTIS Part Ii Submission Date

21-08-2024

Latest Decision Or Authorization Date

30-08-2024

Processing Time Days

9

Number Of Sites

8

Number Of Participants

43

Primary sponsor

Full Name

Exelixis Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

4G Clinical B.V.

Responsibilities

sponsorDuties codes: ["3"]

Name

Icon Clinical Research Limited

Responsibilities

Multiple sponsor duties: codes ["1","11","12","13","2","4","5","8"]

Name

PRA Hellas CRO A.E.

Responsibilities

Multiple sponsor duties: codes ["1","11","12","13","2","4","5","8"]

Third parties

• {"country":"Netherlands","full_name":"4G Clinical B.V.","duties_or_roles":"sponsorDuties codes: [\"3\"]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Ireland","full_name":"Almac Clinical Services (Ireland) Limited","duties_or_roles":"sponsorDuties codes: [\"14\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: [\"7\"]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"ECG analysis/ review","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"sponsorDuties codes: [\"14\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Angle Europe Limited","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Sample management and storage","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Allucent (US) LLC","duties_or_roles":"sponsorDuties codes: [\"10\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Meeting Protocol Worldwide LP","duties_or_roles":"Patient reimbursement","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Alliance Pharma Inc.","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Multiple sponsor duties: codes [\"1\",\"11\",\"12\",\"13\",\"2\",\"4\",\"5\",\"8\"]","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Quipment","duties_or_roles":"Supplying and calibration of medical equipment","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medqia LLC","duties_or_roles":"Medical image analysis/ review","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"PRA Hellas CRO A.E.","duties_or_roles":"Multiple sponsor duties: codes [\"1\",\"11\",\"12\",\"13\",\"2\",\"4\",\"5\",\"8\"]","organisation_type":"Pharmaceutical company"}