Study of Cabozantinib in Combination With Atezolizumab compared to Second Novel Hormonal Therapy (NHT) in Subjects with Metastatic Castration-Resistant Prostate Cancer
- Conditions
- Metastatic Castration-Resistant Prostate CancerMedDRA version: 21.1Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000348-77-GR
- Lead Sponsor
- Exelixis, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Male
- Target Recruitment
- 580
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, and/or mCRPC. Subjects must have had a rising PSA or radiographically progressed on their prior NHT as described above.
3. 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.
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.
b. Soft tissue disease progression (PD) in the opinion of the Investigator.
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
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 intra-abdominal 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, drug-induced 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 hypoth
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of cabozantinib in combination with atezolizumab versus second NHT (abiraterone or enzalutamide) in subjects with first or<br>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.;Secondary Objective: Not applicable;Primary end point(s): • Duration of PFS per RECIST 1.1 per BIRC<br>• Duration of OS;Timepoint(s) of evaluation of this end point: • The primary analysis of PFS is event-driven and will be conducted after at least 202 events have been observed in the PITT population.<br>• The primary analysis of OS is event-driven and will be conducted after at least 340 deaths have been observed in the ITT population.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • ORR per RECIST 1.1 per BIRC;Timepoint(s) of evaluation of this end point: At time of data cutoff, the proportion of subjects for whom the best overall response is a CR or PR as assessed by the BIRC per RECIST 1.1, which is confirmed by a subsequent visit = 28 days later.