Clinical Trials /

IMMU-132 in Patients With Metastatic Castration-Resistant Prostate Cancer Progressing on Second Generation AR-Directed Therapy

NCT03725761

Description:

This study will investigate the safety and efficacy of IMMU-132 in patients with metastatic castration-resistant prostate cancer progressing on abiraterone or enzalutamide.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: IMMU-132 in Patients With Metastatic Castration-Resistant Prostate Cancer Progressing on Second Generation AR-Directed Therapy
  • Official Title: A Study to Evaluate the Safety and Efficacy of IMMU-132 (Sacituzumab Govitecan) in Patients With Metastatic Castration-Resistant Prostate Cancer Who Have Progressed on Second Generation AR-Directed Therapy

Clinical Trial IDs

  • ORG STUDY ID: UW18043
  • SECONDARY ID: P30CA014520
  • SECONDARY ID: A534260
  • SECONDARY ID: SMPH\MEDICINE\HEM-ONC
  • SECONDARY ID: NCI-2018-02551
  • NCT ID: NCT03725761

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
IMMU-132Sacituzumab GovitecanIMMU-132 Treatment

Purpose

This study will investigate the safety and efficacy of IMMU-132 in patients with metastatic castration-resistant prostate cancer progressing on abiraterone or enzalutamide.

Detailed Description

      This study will investigate the safety and efficacy of IMMU-132 in patients with metastatic
      castration-resistant prostate cancer progressing on abiraterone or enzalutamide. Patients who
      have progressed while on therapy with combination enzalutamide/abiraterone or
      ARN-509/abiraterone as part of ongoing clinical trials are allowed and may be enrolled in the
      study. To better understand the heterogeneity of response and in particular to identify
      patients likely to benefit, an extensive correlative biomarker program will be included to
      collect and analyze tumor tissue biopsies, circulating tumor cells (CTCs), and circulating
      tumor DNA (ctDNA).

      A validated predictive biomarker would benefit the individual patient by enabling him to be
      treated with a safe effective oral drug and avoid one from which he is unlikely to benefit.
      It is also essential for prostate cancer drug development because the increasing availability
      of more life-prolonging therapies is making it more difficult to prove a survival benefit for
      the next promising agent.
    

Trial Arms

NameTypeDescriptionInterventions
IMMU-132 TreatmentExperimentalSubjects enrolled in this study will receive IMMU-132 as treatment for Castrate-Resistant Prostate Cancer. Dose will be calculated per protocol in milligrams based on the subject's body weight at the beginning of each cycle or more frequently if weight changes >10%. Subjects will be treated on days 1 and 8 in a 21-day cycle, minimum 3 cycles.
  • IMMU-132

Eligibility Criteria

        Inclusion Criteria:

          -  Documented histological or cytological evidence of adenocarcinoma of the prostate

          -  Documented metastatic disease on bone scan and/or 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 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 RECIST 1.1

               -  Bone disease progression defined by PCWG2 with ≥2 new lesions on bone scan

          -  A minimum serum PSA level of ≥2 ng/mL that is rising based on the PCWG2 criteria

          -  ≥18 y ears of age

          -  Castrate levels of testosterone (<50 ng/dL [1.74 nmol/L])

          -  Undergone orchiectomy, or have been on 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

          -  ECOG Performance Status of 0-1 (Appendix A)

          -  Normal organ function with acceptable initial laboratory values within 30 days of
             study treatment start:

               -  WBC ≥3000/μl

               -  ANC ≥1000/μl

               -  Platelet count ≥100,000/μl

               -  HGB ≥9 g/dL

          -  Adequate hepatic function as evidenced by AST/ALT levels <3X the ULN and bilirubin
             levels of <2.0 mg/dl.

          -  Adequate renal function as evidenced by 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, 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 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 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 QTcF interval of >470 msec on the initial Screening 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.

          -  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 >150mmHg 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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:PSA response rate
Time Frame:up to 9 weeks
Safety Issue:
Description:Subjects who achieve ≥50% PSA decline at or before 9 weeks of therapy with IMMU-132 are considered to have responded. PSA responses will be analyzed by descriptive statistics and summarized in tabular format (frequency tables). The overall PSA response rate will be reported along with the corresponding 95% confidence interval which will be constructed using the Wilson score method.

Secondary Outcome Measures

Measure:6-Month Median Progression Free Survival
Time Frame:6 months
Safety Issue:
Description:Proportion of subjects remaining alive and progression free (using PCWG2 criteria) 6 months from time of starting treatment as estimated by the Kaplan-Meier method.
Measure:Median Progression Free Survival Rate
Time Frame:Up to 2 years from start of treatment
Safety Issue:
Description:The probability distribution of Progression Free Survival (PFS) will be estimated using the Kaplan-Meier method. The median will be estimated from this distribution. Subjects who have not died or progressed (using PCWG2 criteria) will be censored at the date of last assessment.
Measure:Radiologic Response Rate
Time Frame:up to 2 years from start of treatment
Safety Issue:
Description:Number of subjects with reduction in tumor size compared to baseline.
Measure:Median Overall Survival
Time Frame:Up to 2 years from start of treatment
Safety Issue:
Description:Overall Survival (OS) is the duration from start of treatment until death from any cause. The probability distribution of OS will be estimated using the Kaplan-Meier method. The median will be estimated from this distribution. Subjects who have not died will be censored at the date of last contact.
Measure:Toxicity rates (Grade 2, Grade 3, Grade 4, Grade ≥ 2, Grade ≥ 3, etc.)
Time Frame:Up to 9 weeks from start of treatment
Safety Issue:
Description:Toxicities will be summarized by type and severity in tabular format. Toxicity rates (Grade 2, Grade 3, Grade 4, Grade ≥ 2, Grade ≥ 3, etc.) will be calculated and reported along the corresponding 95% confidence intervals. The 95% confidence intervals will be constructed using the Wilson score method.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Wisconsin, Madison

Trial Keywords

  • Prostate

Last Updated

November 18, 2019