Clinical Trials /

Study of Cabozantinib in Combination With Atezolizumab Versus Second NHT in Subjects With mCRPC

NCT04446117

Description:

This is a Phase 3, multi-center, randomized, open-label, controlled study designed to evaluate the safety and efficacy of cabozantinib given in combination with atezolizumab versus a second novel hormonal therapy (NHT) in men with metastatic castration-resistant prostate cancer (mCRPC) who have previously been treated with one, and only one, NHT for their prostate cancer disease.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Cabozantinib in Combination With Atezolizumab Versus Second NHT in Subjects With mCRPC
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: XL184-315
  • NCT ID: NCT04446117

Conditions

  • Metastatic Prostate Cancer
  • Prostate Adenocarcinoma

Interventions

DrugSynonymsArms
CabozantinibXL184, Cabometyx®Experimental Arm
AtezolizumabTecentriq®Experimental Arm
Abiraterone AcetateAbiraterone, ZytigaControl Arm
EnzalutamideXtandiControl Arm
PrednisoneControl Arm

Purpose

This is a Phase 3, multi-center, randomized, open-label, controlled study designed to evaluate the safety and efficacy of cabozantinib given in combination with atezolizumab versus a second novel hormonal therapy (NHT) in men with metastatic castration-resistant prostate cancer (mCRPC) who have previously been treated with one, and only one, NHT for their prostate cancer disease.

Detailed Description

      The primary objective of this study is to evaluate the efficacy of cabozantinib (XL184) in
      combination with atezolizumab versus a second NHT (abiraterone or enzalutamide) in subjects
      with mCRPC who have previously been treated with one, and only one, NHT (e.g. abiraterone,
      apalutamide, darolutamide, or enzalutamide) to treat metastatic castration-sensitive prostate
      cancer (mCSPC), non-metastatic CRPC (M0 CRPC), or mCRPC, and who have measurable extrapelvic
      disease. The multiple primary efficacy endpoints comparing the experimental arm and control
      arm are Duration of Progression Free Survival (PFS) per RECIST 1.1 by Blinded Independent
      Radiology Committee (BIRC) and Duration of Overall Survival (OS). The secondary efficacy
      endpoint is Objective Response Rate (ORR) per RECIST 1.1 per BIRC.
    

Trial Arms

NameTypeDescriptionInterventions
Experimental ArmExperimentalSubjects with mCRPC will receive cabozantinib 40mg oral, qd + atezolizumab 1200mg infusion, q3w
  • Cabozantinib
  • Atezolizumab
Control ArmActive ComparatorSubjects with mCRPC will receive active comparator of EITHER abiraterone 1000mg oral, qd + prednisone 5 mg oral, bid; OR enzalutamide 160mg oral, qd as designated by the Investigator prior to randomization
  • Abiraterone Acetate
  • Enzalutamide
  • Prednisone

Eligibility Criteria

        Inclusion Criteria:

          -  Men with histologically or cytologically confirmed adenocarcinoma of the prostate

          -  Prior treatment with one, and only one, NHT (eg, abiraterone, apalutamide,
             darolutamide, or enzalutamide) for castration-sensitive locally advanced (T3 or T4) or
             mCSPC, M0 CRPC, or mCRPC

          -  Surgical or medical castration, with serum testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at
             screening

          -  Measurable (extrapelvic soft tissue) metastatic disease per Investigator assessment
             defined by at least one of the following: measurable visceral disease (eg, adrenal,
             kidney, liver, lung, pancreas, spleen) per RECIST 1.1; OR measurable extrapelvic
             adenopathy (ie, adenopathy above the aortic bifurcation)

          -  Progressive disease at study entry as defined by specific criteria for prostate
             specific antigen (PSA) progression OR soft tissue disease progression in the opinion
             of the Investigator (Note: subjects with bone disease progression alone are not
             eligible)

          -  Age ≥ 18 years old or meeting country definition of adult, whichever is older, on the
             day of consent

          -  ECOG performance status of 0 or 1

          -  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

          -  Adequate organ and marrow function based upon specific laboratory assessments obtained
             within 21 days prior to randomization

          -  Understanding and ability to comply with protocol requirements

        Exclusion Criteria:

          -  Any prior nonhormonal therapy initiated for the treatment of mCRPC

          -  Receipt of abiraterone within 1 week; cyproterone within 10 days; or flutamide,
             nilutamide, bicalutamide, enzalutamide, or other androgen-receptor inhibitors within 2
             weeks before randomization

          -  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)

          -  Known brain metastases or cranial epidural disease unless adequately treated and
             clinically stable at least 4 weeks prior to randomization

          -  Symptomatic or impending spinal cord compression or cauda equina syndrome

          -  Concomitant anticoagulation with oral anticoagulants (some specific exceptions apply)

          -  Administration of a live, attenuated vaccine within 30 days prior to randomization

          -  Systematic treatment with, or any condition requiring, either corticosteroids (>10 mg
             daily prednisone equivalent) or other immunosuppressive medications within 14 days
             prior to randomization

          -  Uncontrolled, significant intercurrent or recent illness

          -  Major surgery within 4 weeks prior to randomization

          -  Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per ECG
             within 21 days before randomization

          -  Inability or unwillingness to swallow pills or receive IV administration

          -  Previously identified allergy or hypersensitivity to components of the study treatment
             formulations or history of severe infusion-related reactions to monoclonal antibodies

          -  Any other active malignancy at time of randomization or diagnosis of another
             malignancy within 2 years prior to randomization that requires active treatment (some
             exceptions apply such as locally curable cancers that have apparently been cured).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Duration of Progression Free Survival per Response Evaluable Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Time Frame:Approximately 21 months after the first subject is randomized.
Safety Issue:
Description:Defined as time from randomization to the earlier of progressive disease (PD) per RECIST 1.1 as determined by the Blinded Independent Radiology Committee (BIRC) or death from any cause

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Approximately 37 months after the first subject is randomized
Safety Issue:
Description:ORR per RECIST 1.1 by BIRC

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Exelixis

Trial Keywords

  • prostate cancer
  • castration-resistant prostate cancer

Last Updated

June 30, 2020