AzTrials
AzTrials

Prostate CancerPhase 2SPARCNCT03964337

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

A Phase 2 study testing Cabozantinib and Radical Prostatectomy in people with Prostate Cancer and Prostate Cancer Adenocarcinoma, run by Duke University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Cabozantinib and Radical Prostatectomy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
17 Mar 2020to 4 Jun 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 23Show fewer
  • 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
  • Hemoglobin ≥9.0 g/dL
  • Serum calcium ≤12.0 mg/dL
  • Serum creatinine ≤ 2.0 x ULN or calculated creatinine clearance ≥ 30mL/min.
  • Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol).
  • Written Authorization for Use and Release of Health and Research Study Information (HIPAA authorization per institutional requirements)
  • Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.
  • Willing/able to adhere to the prohibitions and restrictions specified in this protocol.
  • Agrees to use a condom (even men with vasectomies) and another effective method of birth control if subject is having sex with a woman who is pregnant or a woman of childbearing potential while on study drug and for 4 months following the last dose of study drug.

Who cannot join

  • 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).
Show all 24Show fewer
  • 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:
  • Cardiovascular disorders:
  • 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.
  • 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.
  • Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
  • 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.
  • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose.
  • Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose.
  • Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose.
  • Serious non-healing wound/ulcer/bone fracture. e. Other clinically significant disorders that would preclude safe study participation.
  • Hypertension that cannot be controlled by medications (>140/90 mm Hg despite optimal medical therapy).
  • Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.
  • Concurrent treatment on another clinical trial. Supportive care trials or non-treatment trials, e.g. QOL, are allowed.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
  • Inability to swallow tablets.
  • Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Duke University Medical Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: A Phase II, Open-Label Randomized Study of Immediate Prostatectomy vs. Cabozantinib Followed by Prostatectomy in Men With High-Risk Prostate Cancer (SPARC)

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.

Being tested
Cabozantinib, Radical Prostatectomy
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CabozantinibDrug

    Also called Cabometyx

    Cabozantinib 40 mg by mouth daily for 4 weeks.

  • Radical ProstatectomyProcedure or surgery

    Radical prostatectomy as part of routine medical care.

Study groups in NCT03964337
Study groupRoleWhat they receive
Cabozantinib Followed by Prostatectomy (Arm A)ExperimentalExperimental group will received cabozantinib for 4 weeks, followed by a 2 week drug washout before a prostatectomy.
Receives: Drug: Cabozantinib; Procedure: Radical Prostatectomy
Immediate Prostatectomy (Arm B)Active comparatorControl group will receive an immediate prostatectomy.
Receives: Procedure: Radical Prostatectomy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

Secondary outcomes (13)
  1. Immune Phenotyping of Myeloid-derived Suppressor Cells (MDSCs)

    Percentage of MDSCs in peripheral blood and tumor tissue

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

  2. Immune Phenotyping of Neutrophils

    Percentage of neutrophils in peripheral blood and tumor tissue

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

  3. Immune Phenotyping of M1 Macrophages

    Percentage of M1 macrophages in peripheral blood and tumor tissue

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

  4. Immune Phenotyping of M2 Macrophages

    Percentage of M2 macrophages in peripheral blood and tumor tissue

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

  5. Immunohistochemical (IHC) Analysis of CD8+

    Percentage of CD8+ positive cells in tumor tissue

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

  6. Immunohistochemical (IHC) Analysis of Programmed Death Ligand-1 (PD-L1)

    Percentage of PD-L1 positive cells in tumor tissue

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

  7. Immunohistochemical (IHC) Analysis of Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4)

    Percentage of CTLA-4 positive cells in tumor tissue

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

  8. Immunohistochemical (IHC) Analysis of Interleukin-1 Receptor Antagonist (IL-1RA)

    Percentage of IL-1RA positive cells in tumor tissue

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

  9. Description of the Neutrophil Chemotactic Factor CXCL12

    Percentage of neutrophil chemotactic factor CXCL12 positive cells in tumor tissue

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

  10. Description of the Neutrophil Chemotactic Factor HMGB1

    Percentage of neutrophil chemotactic factor HMGB1 positive cells in tumor tissue

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

  11. Description of the MDSC-promoting Cytokine CCL5

    Percentage of MDSC-promoting cytokine CCL5 positive cells in tumor tissue

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

  12. Description of the MDSC-promoting Cytokine CCL12

    Percentage of MDSC-promoting cytokine CCL12 positive cells in tumor tissue

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

  13. Description of the MDSC-promoting Cytokine CD40

    Percentage of MDSC-promoting cytokine CD40 cells in tumor tissue

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 May 2019
  2. Study start17 Mar 2020
  3. Primary completion4 Jun 2021
  4. Study completion4 Jun 2021

Why it stopped: Poor accrual.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03964337
Sponsor's protocol ID
Pro00101042
Acronym
SPARC
Status last verified
Jun 2022
First submitted
23 May 2019
Last updated
29 Jun 2022
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib and Radical Prostatectomy in people with Prostate Cancer and Prostate Cancer Adenocarcinoma, run by Duke University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Apoptotic Index in Prostatectomy Specimens From Patients Who Undergo Immediate Prostatectomy (Arm B) Versus Those Treated With Cabozantinib Followed by Prostatectomy (Arm A) (time frame: At prostatectomy (Arm A: Day 43, Arm B: Day 1)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2022.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in