Sacituzumab Govitecan in Treating Patients with Metastatic Castration-Resistant Prostate Cancer Who Have Progressed on Second Generation Androgen Receptor-Directed Therapy

Status: Active

Description

This phase II trial studies how well sacituzumab govitecan works in treating patients with castration-resistant prostate cancer that has spread to other places in the body and progressed on second generation androgen receptor-directed therapy. Immunotherapy with sacituzumab govitecan may induce changes in the body’s immune system and may interfere with the ability of tumor cells to grow and spread.

Eligibility Criteria

Inclusion Criteria

  • Documented histological or cytological evidence of adenocarcinoma of the prostate
  • Documented metastatic disease on bone scan and/or computed tomography (CT) scans
  • Received enzalutamide, abiraterone, or apalutamide. Subjects who have received combination enzalutamide/abiraterone or combination ARN-509/abiraterone as part of ongoing clinical trials are allowed. Subjects who have received TAK-700 (Orteronel), TOK-001 (Galeterone), or any other therapeutic investigational product directed towards the androgen receptor (AR) or androgen biosynthesis are allowed. Prior treatment with first-generation AR antagonists (i.e., bicalutamide, nilutamide, flutamide) before second generation AR-directed therapy is allowed
  • Demonstrated disease progression while on enzalutamide, apalutamide, and/or abiraterone. Progressive disease is defined by one or more of the following: * A rise in PSA on two successive determinations at least one week apart and PSA level >= 2 ng/mL * Soft-tissue progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * Bone disease progression defined by Prostate Cancer Working Group (PCWG)2 with >= 2 new lesions on bone scan
  • A minimum serum PSA level of >= 2 ng/mL that is rising based on the PCWG2 criteria
  • Castrate levels of testosterone (< 50 ng/dL [1.74 nmol/L])
  • Undergone orchiectomy, or have been on luteinizing hormone-releasing hormone (LHRH) agonists or antagonists, for at least 3 months prior to study treatment start. Subjects on LHRH agonists/antagonists must remain on these agents for the duration of the study
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • White blood cell (WBC) >= 3000/ul (within 30 days of study treatment start)
  • Absolute neutrophil count (ANC) >= 1000/ul (within 30 days of study treatment start)
  • Platelet count >= 100,000/ul (within 30 days of study treatment start)
  • Hemoglobin (HGB) >= 9 g/dL (within 30 days of study treatment start)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels < 3 X the upper limit of normal (ULN)
  • Bilirubin levels of < 2.0 mg/dl
  • Serum creatinine of < 2.0 mg/dL
  • Able to provide written informed consent, or have a legal representative provide written informed consent
  • Discontinued enzalutamide, apalutamide, or abiraterone >= 4 weeks prior to study drug initiation
  • Subjects must have a previously-acquired biopsy from a metastatic site available
  • Subjects must be willing and able (in the opinion of the treating physician) to undergo one research biopsy for the investigational component of this study
  • Subjects who have partners of child-bearing potential must be willing to use at least two forms of effective birth control (one form must be a barrier method) during the treatment period and for 90 days after last dose of IMMU-132. Subjects must also agree to not donate sperm through 90 days following the last dose of IMMU-132

Exclusion Criteria

  • Received prior cytotoxic chemotherapy for CRPC. Prior docetaxel for castration-sensitive disease is permitted
  • Received more than one second generation, Food and Drug Administration (FDA) approved, AR-directed line of therapy: i.e., sequential enzalutamide-abiraterone or abiraterone-enzalutamide will not be allowed
  • Completed sipuleucel-T (Provenge) treatment within 30 days of study treatment start
  • Received any therapeutic investigational agent within 2 weeks of study treatment start
  • Received palliative radiotherapy within 4 weeks of study treatment start
  • Received herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity (e.g., saw palmetto, PC-SPES, PC-HOPE, St. John’s wort, selenium supplements, grape seed extract, etc.) within 4 weeks of study treatment start or plans to initiate treatment with these products/alternative therapies during the entire duration of the study
  • Active central nervous system (CNS) metastases from prostate cancer. Subjects with treated epidural disease are eligible to enroll. Subjects with treated brain metastases can be included as long as > 4 weeks have elapsed since last treatment (radiotherapy or surgery) for brain metastases, the subject is neurologically and radiographically stable, and is not receiving corticosteroids for brain metastases. Subjects with untreated brain metastases are excluded. Brain imaging (CT or magnetic resonance imaging [MRI]) is not required at baseline if brain metastases are not clinically suspected
  • A history within the last 3 years of another invasive malignancy (excluding non-melanoma skin cancer)
  • A corrected QT using Fridericia's formula (QTcF) interval of > 470 msec on the initial screening electrocardiogram (ECG); if the screening ECG QTcF interval is > 470 msec, then it may be repeated two more times, and if the mean QTcF of the 3 ECGs is =< 470 msec, the subject may be enrolled
  • A history of clinically significant cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation, torsades de pointes and second degree or third degree atrioventricular heart block without a permanent pacemaker in place. Subjects with resolved or rate-controlled atrial fibrillation/atrial flutter are allowed
  • New York Heart Association (NYHA) class III or IV congestive heart failure, unstable angina, myocardial infarction/acute coronary syndrome within the preceding 6 months
  • Diabetes mellitus with more than 2 episodes of diabetic ketoacidosis in the 12 months preceding study treatment start
  • Inadequately controlled hypertension (defined as blood pressure > 150 mmHg systolic and/or > 100 mmHg diastolic despite antihypertensive medication) or any history of hypertensive crisis or hypertensive encephalopathy
  • History of loss of consciousness or transient ischemic attack within 12 months before study treatment start
  • Known active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infections
  • Any other medical, psychiatric, or social condition, including substance abuse, which in the opinion of the investigator would preclude safe participation in the study

Locations & Contacts

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Rebecca Green
Phone: 646-888-1313
Email: borsukr@mskcc.org
NYP / Weill Cornell Medical Center
Status: Active
Contact: Jyoti Sreekumar
Phone: 646-962-9340
Email: jys2004@med.cornell.edu

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Contact: Mary Jane Staab
Phone: 608-263-4304
Email: Mjs@medicine.wisc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the proportion of subjects who have >= 50% prostate specific antigen (PSA) decline at or within 9 weeks of starting treatment with sacituzumab govitecan (IMMU-132).

SECONDARY OBJECTIVES:

I. To determine median radiological progression free survival (rPFS) and 6-month rPFS rate

II. To determine radiologic response rate.

III. To determine overall survival (OS).

IV. To determine safety and tolerability.

EXPLORATORY OBJECTIVES:

I. To associate predictive biomarkers with clinical outcomes to IMMU-132 in castration-resistant prostate cancer (CRPC) subjects who have progressed while on enzalutamide, apalutamide, or abiraterone.

OUTLINE:

Patients receive sacituzumab govitecan intravenously (IV) over 1.5-2 hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 3 months for up to 2 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Wisconsin Hospital and Clinics

Principal Investigator
Christos Kyriakopoulos

Trial IDs

Primary ID UW18043
Secondary IDs NCI-2018-02551, 2018-1779
Clinicaltrials.gov ID NCT03725761