Immediate Prostatectomy vs. Cabozantinib Followed by Prostatectomy in Men With High-Risk Prostate Cancer

NCT03964337 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: Pro00101042
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, randomized, open-label, phase II trial of cabozantinib in subjects with untreated, high risk prostate cancer undergoing radical prostatectomy. This multicenter study will enroll 30 subjects. Duke is the lead site for this trial. There will be a second site selected TBD. Patients will be assigned (first 9 subjects only) or randomized 2:1 to either: (1) cabozantinib 40 mg by mouth daily for 4 weeks, followed by a 2 week drug washout period before prostatectomy (n = 20), or (2) immediate prostatectomy within 12 weeks of registration (n = 10). The first 9 subjects (6 subjects assigned to cabozantinib treatment, 3 subjects assigned to immediate prostatectomy) will constitute the Safety Lead-In Cohort, which will be only accrued at Duke. After six subjects have received cabozantinib and completed the 57-85 day safety visit without triggering a stopping rule, subjects may be accrued at the ex-Duke site. The primary goal is to compare pathologic apoptotic indices (cleaved caspase-3) in prostatectomy specimens from patients who undergo immediate prostatectomy (controls) versus those who receive with cabozantinib followed by prostatectomy. The secondary objective is to conduct immune phenotypic profiling on the peripheral blood and tumor microenvironment in prostatectomy specimens from both groups. A statistical analysis will be used to compare the apoptotic indices between the two groups.

Conditions

Prostate Cancer; Prostate Cancer Adenocarcinoma; Non-Metastatic

Outcome Measures

Primary Outcomes (1)

• Apoptotic Index in Prostatectomy Specimens From Patients Who Undergo Immediate Prostatectomy (Arm B) Versus Those Treated With Cabozantinib Followed by Prostatectomy (Arm A)

  Apoptotic index as measured by cleaved caspase-3 levels in tumor tissue

  At prostatectomy (Arm A: Day 43, Arm B: Day 1)

Secondary Outcomes (13)

• Immune Phenotyping of Myeloid-derived Suppressor Cells (MDSCs)

  Arm A: Screening, Day 29, Day 43, Day 57-85; Arm B: Screening, Day 1

• Immune Phenotyping of Neutrophils

  Arm A: Screening, Day 29, Day 43, Day 57-85; Arm B: Screening, Day 1

• Immune Phenotyping of M1 Macrophages

  Arm A: Screening, Day 29, Day 43, Day 57-85; Arm B: Screening, Day 1

• Immune Phenotyping of M2 Macrophages

  Arm A: Screening, Day 29, Day 43, Day 57-85; Arm B: Screening, Day 1

• Immunohistochemical (IHC) Analysis of CD8+

  At prostatectomy (Arm A: Day 43, Arm B: Day 1)

Study Arms (2)

Cabozantinib Followed by Prostatectomy (Arm A)

EXPERIMENTAL

Experimental group will received cabozantinib for 4 weeks, followed by a 2 week drug washout before a prostatectomy.

Drug: Cabozantinib; Procedure: Radical Prostatectomy

Immediate Prostatectomy (Arm B)

ACTIVE COMPARATOR

Control group will receive an immediate prostatectomy.

Procedure: Radical Prostatectomy

Interventions

Cabozantinib DRUG

Cabozantinib 40 mg by mouth daily for 4 weeks.

Also known as: Cabometyx

Cabozantinib Followed by Prostatectomy (Arm A)

Radical Prostatectomy PROCEDURE

Radical prostatectomy as part of routine medical care.

Cabozantinib Followed by Prostatectomy (Arm A); Immediate Prostatectomy (Arm B)

Eligibility Criteria

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

You may qualify if:

• Male, age ≥ 18 years old.
• ECOG performance status of 0 or 1
• Histologic evidence of adenocarcinoma of the prostate who are deemed candidates for curative radical prostatectomy.
• Planned robotic or laparoscopic prostatectomy technique.
• Low risk for conversion to open prostatectomy, in the opinion of the treating surgeon.
• Intermediate-high or high risk, clinically localized disease by the following criteria:
• Prostate cancer in at least 2 cores with a Gleason score ≥ 7 (4+3 or 3+4) in at least 1 of those cores.
• No definite evidence of metastasis, in the opinion of the investigator.
• Adequate organ function as defined by the following criteria within 14 days prior to first dose of study treatment:
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 x local laboratory upper limit of normal (ULN)
• Total serum bilirubin ≤1.5 x ULN, (for subjects with Gilbert's disease ≤ 3 x ULN)
• Absolute neutrophil count (ANC) ≥1500/L without granulocyte colony-stimulating factor support.
• White blood cell count ≥ 2500/mm3
• Serum albumin ≥ 2.8 g/dl
• Platelets ≥100,000/mm3

You may not qualify if:

• Prior treatment for prostate cancer.
• Major surgery or radiation therapy within 4 weeks of Day 1 on study.
• Planned radiation therapy until at least 4 weeks after prostatectomy.
• NCI CTCAE v4.0 grade 3 hemorrhage within 4 weeks of Day 1 on study.
• Prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 14 days before Day 1 on study (Arm A subjects only) or within 14 days of the completion of screening (Arm B subjects only).
• Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel). However, low-dose aspirin for cardio protection is allowed (per local applicable guidelines).
• History of or known metastatic prostate cancer.
• QTcf interval \> 500 msec on baseline EKG.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• a. Cardiovascular disorders:
• i. Symptomatic congestive heart failure (CHF) New York Heart Association Class 3 or 4, unstable angina pectoris, ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2. coronary/peripheral artery bypass graft (CABG), within 6 months prior to screening.
• ii. Stroke (including transient ischemic attack \[TIA\]), cerebrovascular accident (CVA), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism (PE)) within 6 months prior to screening.
• b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
• i. Evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
• ii. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose.

Sponsors & Collaborators

• Duke University: lead
• Exelixis: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, 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

Study accrual was discontinued prior to enrolling any participants in the control arm (Immediate Prostatectomy, Arm B).

Results Point of Contact

• Title: Michael Harrison, M.D.
• Organization: Duke University

michael.harrison@duke.edu

919-668-8108

Study Officials

• Michael Harrison, MD

  Duke Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2019
• First Posted: May 28, 2019
• Study Start: March 17, 2020
• Primary Completion: June 4, 2021
• Study Completion: June 4, 2021
• Last Updated: June 29, 2022
• Results First Posted: June 29, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)