Study of Cabozantinib in Combination With Atezolizumab Versus Second NHT in Subjects With mCRPC (CONTACT-02)

• ClinicalTrials.gov Identifier: NCT04446117
• Recruitment Status: Recruiting
• First Posted: June 24, 2020
• Last Update Posted: March 31, 2023
• Sponsor: Exelixis
• Collaborators: Roche-Genentech; Takeda
• Information provided by (Responsible Party): Exelixis

Tracking Information

• First Submitted Date: June 22, 2020
• First Posted Date: June 24, 2020
• Last Update Posted Date: March 31, 2023
• Actual Study Start Date: June 30, 2020
• Estimated Primary Completion Date: June 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 22, 2020)

• 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. ]
  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
• Duration of Overall Survival (OS) [ Time Frame: Approximately 37 months after the first subject is randomized ]
  Defined as time from randomization to date of death from any cause

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 22, 2020)

Objective response rate (ORR) [ Time Frame: Approximately 37 months after the first subject is randomized ]

ORR per RECIST 1.1 by BIRC

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief Summary: 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.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Approximately 580 eligible subjects will be randomized in a 1:1 fashion to the experimental arm receiving cabozantinib and atezolizumab in combination (290) or to the control arm receiving a second NHT (290).

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Metastatic Prostate Cancer
• Prostate Adenocarcinoma

Intervention

• Drug: Cabozantinib
  Supplied as 20-mg tablets; administered orally daily at 40mg
  Other Names:

  • XL184
  • Cabometyx®
• Drug: Atezolizumab
  Supplied as 1200 mg/20 mL vials; administered as an IV infusion once every 3 weeks (q3w)
  Other Name: Tecentriq®
• Drug: Abiraterone Acetate
  Supplied as 500 mg tablets; administered orally daily at 1000mg with prednisone 5 mg orally bid
  Other Names:

  • Abiraterone
  • Zytiga
• Drug: Enzalutamide
  Supplied as 40 mg capsules; administered orally daily at 160mg
  Other Name: Xtandi
• Drug: Prednisone
  Supplied as 5 mg tablets; administered orally bid at 5 mg with abiraterone 1000mg orally daily

Study Arms

• Experimental: Experimental Arm
  Subjects with mCRPC will receive cabozantinib 40mg oral, qd + atezolizumab 1200mg infusion, q3w
  Interventions:

  • Drug: Cabozantinib
  • Drug: Atezolizumab
• Active Comparator: Control Arm
  Subjects 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
  Interventions:

  • Drug: Abiraterone Acetate
  • Drug: Enzalutamide
  • Drug: Prednisone

• Publications *: Agarwal N, Azad A, Carles J, Chowdhury S, McGregor B, Merseburger AS, Oudard S, Saad F, Soares A, Benzaghou F, Kerloeguen Y, Kimura A, Mohamed N, Panneerselvam A, Wang F, Pal S. A phase III, randomized, open-label study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy in patients with metastatic castration-resistant prostate cancer. Future Oncol. 2022 Mar;18(10):1185-1198. doi: 10.2217/fon-2021-1096. Epub 2022 Jan 17.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 22, 2020): 580
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2024
• Estimated Primary Completion Date: June 30, 2023 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Exelixis Clinical Trials; 1-888-EXELIXIS (888-393-5494); druginfo@exelixis.com

Contact: Backup or International; 650-837-7400

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czechia, France, Georgia, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Poland, Portugal, Russian Federation, Singapore, Spain, Taiwan, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04446117
• Other Study ID Numbers: XL184-315
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Exelixis
• Original Responsible Party: Same as current
• Current Study Sponsor: Exelixis
• Original Study Sponsor: Same as current

Collaborators

• Roche-Genentech
• Takeda

• Investigators: Not Provided
• PRS Account: Exelixis
• Verification Date: March 2023