Cabozantinib and Abiraterone With Checkpoint Inhibitor Immunotherapy in Metastatic Hormone Sensitive Prostate Cancer (CABIOS Trial)

NCT04477512 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 202009082
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to determine the recommended phase 2 dose of the multi-drug combination of abiraterone, cabozantinib, and nivolumab in conjunction with ongoing androgen deprivation therapy in previously untreated metastatic hormone-sensitive prostate cancer patients. The investigators hypothesize that the combination of cabozantinib and abiraterone acetate/prednisone in conjunction with nivolumab will have an acceptable safety profile and will be feasible to administer in patients with hormone-sensitive metastatic prostate cancer.

Conditions

Metastatic Hormone Refractory Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Frequency of dose-limiting toxicities (DLTs)

  * Protocol defined hematologic DLTs that occur during the first cycle that are attributed as possibly, probably, or definitely related to study treatment * Protocol defined non-hematologic DLTs possibly, probably, or definitely related grade 3 or 4 non-hematologic toxicity that occurs during the first cycle of treatment.

  Completion of 1st cycle of treatment for patients in dose level 1 & dose level 2 (estimated to be 11 months)

Secondary Outcomes (8)

• PSA response rate

  Through end of treatment (estimated to be 24 months)

• Overall response rate (ORR)

  Through end of treatment (estimated to be 24 months)

• Overall survival (OS)

  From start of treatment through 1 year of follow-up (estimated to be 36 months)

• Progression-free survival (PFS)

  From start of treatment through 1 year of follow-up (estimated to be 36 months)

• Disease specific survival (DSS)

  From start of treatment through 1 year of follow-up (estimated to be 36 months)

Study Arms (3)

Level 1: Cabozantinib+Abiraterone acetate +Nivolumab

EXPERIMENTAL

-Abiraterone acetate is an oral medication given at a dose of 1000 mg daily. Prednisone is an oral medication given at a dose of 5 mg daily. Nivolumab is given intravenously over 30 minutes on Day 1 of each 28-day cycle at a dose of 480 mg. Cabozantinib is an oral drug given daily; dosing will be 20 mg. Participants can continue to receive treatment for up to 2 years.

Drug: Cabozantinib; Drug: Nivolumab; Drug: Abiraterone acetate; Drug: Prednisone; Procedure: Peripheral blood collection

Level 2: Cabozantinib+Abiraterone acetate +Nivolumab

EXPERIMENTAL

-Abiraterone acetate is an oral medication given at a dose of 1000 mg daily. Prednisone is an oral medication given at a dose of 5 mg daily. Nivolumab is given intravenously over 30 minutes on Day 1 of each 28-day cycle at a dose of 480 mg. Cabozantinib is an oral drug given daily; dosing will be 40 mg. Participants can continue to receive treatment for up to 2 years.

Drug: Cabozantinib; Drug: Nivolumab; Drug: Abiraterone acetate; Drug: Prednisone; Procedure: Peripheral blood collection

Expansion: Cabozantinib+Abiraterone acetate +Nivolumab

EXPERIMENTAL

-Abiraterone acetate is an oral medication given at a dose of 1000 mg daily. Prednisone is an oral medication given at a dose of 5 mg daily. Nivolumab is given intravenously over 30 minutes on Day 1 of each 28-day cycle at a dose of 480 mg. Cabozantinib is an oral drug given daily; dosing will be dependent on recommended dose found in first part of study. Participants can continue to receive treatment for up to 2 years.

Drug: Cabozantinib; Drug: Nivolumab; Drug: Abiraterone acetate; Drug: Prednisone; Procedure: Peripheral blood collection

Interventions

Cabozantinib DRUG

Supplied by Exelixis

Expansion: Cabozantinib+Abiraterone acetate +Nivolumab; Level 1: Cabozantinib+Abiraterone acetate +Nivolumab; Level 2: Cabozantinib+Abiraterone acetate +Nivolumab

Nivolumab DRUG

Supplied by Bristol-Myers Squibb

Expansion: Cabozantinib+Abiraterone acetate +Nivolumab; Level 1: Cabozantinib+Abiraterone acetate +Nivolumab; Level 2: Cabozantinib+Abiraterone acetate +Nivolumab

Abiraterone acetate DRUG

Commercially available

Expansion: Cabozantinib+Abiraterone acetate +Nivolumab; Level 1: Cabozantinib+Abiraterone acetate +Nivolumab; Level 2: Cabozantinib+Abiraterone acetate +Nivolumab

Prednisone DRUG

Commercially available

Expansion: Cabozantinib+Abiraterone acetate +Nivolumab; Level 1: Cabozantinib+Abiraterone acetate +Nivolumab; Level 2: Cabozantinib+Abiraterone acetate +Nivolumab

Peripheral blood collection PROCEDURE

Prior to start of treatment, after 8 weeks of combination therapy, with every subsequent imaging (every 12 weeks), end of treatment

Expansion: Cabozantinib+Abiraterone acetate +Nivolumab; Level 1: Cabozantinib+Abiraterone acetate +Nivolumab; Level 2: Cabozantinib+Abiraterone acetate +Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed hormone-sensitive prostate adenocarcinoma.
• Must have evidence of metastatic disease on CT or MRI of the chest, abdomen, and pelvis, or technetium bone scan. May have any type or location of metastases (bone, lymph node, visceral). May have relapsed metastatic disease after initial primary therapy or de novo metastatic disease. Metastatic disease does not have to be confirmed by biopsy.
• May have been on androgen deprivation therapy (ADT) for metastatic hormone-sensitive prostate cancer for ≤ 12 weeks prior to study enrollment (GnRHR agonist such as leuprolide, goserelin, triptorelin, buserelin, histrelin; GnRHR antagonists such as degarelix, or relugolix). Prior ADT for localized prostate cancer is allowed.
• Prior palliative radiation therapy for bone metastasis (must be complete ≥14 days prior to enrollment) or any other radiation therapy (must be complete ≥28 days prior to enrollment) is allowed. Prior definitive radiation therapy for localized prostate cancer is allowed.
• If the patient has undergone bilateral orchiectomy, it must have occurred no more than 12 weeks before study enrollment.
• Recovery to baseline or ≤ grade 1 from toxicities related to any prior treatments, unless AEs are clinically nonsignificant and/or stable on supportive therapy.
• At least 18 years of age.
• ECOG performance status ≤ 1
• Normal bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1,500 K/cumm without granulocyte colony-stimulating factor support
• White blood cell count ≥ 2,500 K/cumm
• Platelets ≥ 100,000 K/cumm without transfusion
• Hemoglobin ≥ 9.0 g/DL
• Total bilirubin ≤ 1.5 x IULN (for subjects with Gilbert's disease ≤ 3.0 x IULN)
• AST(SGOT), ALT(SGPT), and alkaline phosphatase (ALP) ≤ 3.0 x IULN; ALP ≤ 5.0 x IULN with documented bone metastases

You may not qualify if:

• Any evidence of neuroendocrine/small cell prostate cancer, or castrate resistant prostate cancer, as defined by defined by disease progression despite androgen depletion therapy (ADT), either by continuous rise in serum PSA levels as measured over at least 2 consecutive values, or the clinical or radiographic progression of disease, as assessed by the investigator.
• Prior exposure to second-generation androgen receptor inhibitors (e.g., enzalutamide, apalutamide, darolutamide).
• Prior exposure to CYP17 inhibitors (e.g. abiraterone)
• No chronic concomitant treatment with strong cytochrome P450 (CYP) 3A4 inducers or inhibitors. If patients are on such agents and these can be safely discontinued, may not have received a strong CYP3A4 inducer/inhibitor within 5 half-lives.
• Prior systemic chemotherapy for prostate cancer (either for localized or metastatic disease). Patients may have received androgen deprivation therapy (ADT) for \< 12 weeks prior to start of study drug; no other cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
• Prior treatment with checkpoint inhibitor or other immunotherapy (e.g., anti-PD-1, anti-PD-L1, anti-CTLA4).
• Prior treatment with cabozantinib.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• Inability to swallow pills.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohns disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Bristol-Myers Squibb: collaborator
• Exelixis: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Interventions

cabozantinib; Nivolumab; Abiraterone Acetate; Prednisone

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Study Officials

• Russell K Pachynski, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: July 20, 2020
• Study Start: February 19, 2021
• Primary Completion: September 9, 2021
• Study Completion: September 10, 2025
• Last Updated: November 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)