Cabozantinib in Patients With Metastatic Castrate Resistant Prostate Cancer (mCRPC)

NCT04631744 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 19-04020287
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine what effects (good and bad) cabozantinib has in treatment of patients with metastatic castrate resistant prostate cancer (mCRPC). The hypothesis for this trial is that cabozantinib has anti-tumor activity in a molecularly-selected group of patients with CRPC or patients with liver metastases.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Median Radiographic Progression-free Survival (rPFS) Using Kaplan-Meier Methodology

  Radiographic progression will be assessed based on PCWG-modified RECIST 1.1 criteria for soft-tissue lesions and protocol-specific criteria for bone lesions. Progressive disease (PD) for soft-tissue lesions is defined as an increase ≥ 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started, or the appearance of one or more new lesions, or the appearance of new lesions. Progressive disease (PD) criteria for bone lesions is assessing whether there are either "no new lesions" or "new lesions", which will be confirmed on a second scan performed 6 or more weeks later. Radiographic progress-free survival (rPFS) is defined as time from start of treatment to minimum of radiographic progression.

  From initiation of treatment to minimum of radiographic progression, approximately 6 months.

Secondary Outcomes (4)

• Change in Prostate Specific Antigen (PSA)

  From initiation of treatment to minimum of radiographic progression, at approximately 6 months after start of treatment.

• Overall Survival (OS)

  Patients will be followed every 12 weeks up to 2 years after completion of study

• Number of Patients With a Tumor Response

  From initiation of treatment to minimum of radiographic progression, at approximately 6 months after start of treatment.

• Number of Adverse Events

  From the time of signing consent through their End of Treatment visit, which is 30 days after the date of the last dose of cabozantinib treatment, approximately 12 months.

Study Arms (1)

Cabozantinib Arm

EXPERIMENTAL

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Subjects will receive cabozantinib orally at a (starting) dose of 40 mg once daily

Cabozantinib Arm

Eligibility Criteria

• Age: 18 Years - 99 Years
• Gender Eligibility Details: Men with Metastatic Castrate Resistant Prostate Cancer (mCRPC)
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years.
• Documented histological or cytological diagnosis of prostate carcinoma.
• Evidence of metastatic PC on imaging (bone scan and/or CT/MRI scan)
• \- Patients with liver metastases must have biopsy proven evidence of metastatic prostate cancer in the liver.
• Agree to undergo a biopsy of at least one metastatic site or primary prostate prior to beginning therapy. Adequate archival metastatic tissue can be used if available in lieu of a biopsy if done when patient had CRPC and within 6 months of the start of treatment.
• Agree to undergo a biopsy of at least one metastatic site or primary prostate after 3 weeks of therapy (biopsy must be between day 21 and day 24 of treatment). Re-biopsy of same pre-treatment biopsy soft tissue site especially liver metastases is preferred.
• Serum testosterone level less than 50 ng/dl. Subjects without prior orchiectomy must be currently taking and willing to continue luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) therapy until permanent discontinuation of study treatment.
• Documented progressive metastatic CRPC based on at least one of the following criteria:
• PSA progression according to Prostate Cancer Working Group 3 (PCWG3) criteria
• Objective radiographic progression, according to PCWG3 criteria
• ECOG performance status of 0-1
• Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless specified below or AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
• Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support
• White blood cell count ≥ 2500/mm\^3 (≥ 2.5 GI/L)

You may not qualify if:

• 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.
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) except agents to maintain castrate status within 4 weeks before first dose of study treatment. Antiresportive bone agents are also allowed.
• Subject has received abiraterone acetate or enzalutamide within 2 weeks before enrollment.
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment for neurological indications at the time of first dose of study treatment.
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 14 days before the first dose of study treatment.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• Uncontrolled hypertension defined as sustained blood pressure (BP) \>140 mm Hg systolic or \>90 mm Hg diastolic despite optimal antihypertensive treatment.
• Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g. deep venous thrombosis, pulmonary embolism) within 6 months before first dose.

Sponsors & Collaborators

• Exelixis: collaborator
• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Limitations and Caveats

Due to low accrual, the sample size was not sufficient for the statistical analysis plan as written. Therefore, only descriptive statistics can be presented for the study.

Results Point of Contact

• Title: Dr. David Nanus
• Organization: Weill Cornell Medicine

dnanus@med.cornell.edu

646-962-2072

Study Officials

• David M Nanus, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2020
• First Posted: November 17, 2020
• Study Start: March 3, 2021
• Primary Completion: May 12, 2025
• Study Completion: November 9, 2025
• Last Updated: May 1, 2026
• Results First Posted: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)