TheranosticTrials.org

Clinical Trial · NCT03939689

I-131-1095 Radioligand Plus Enzalutamide vs Enzalutamide for mCRPC That Progressed During Abiraterone (ARROW).

Overview

This clinical trial was done to show whether a radioactive drug (I-131-1095) that binds to prostate-specific membrane antigen (PSMA) is useful in treating metastatic prostate cancer that is positive for PSMA. The trial enrolled men whose PSMA-positive metastatic prostate cancer had progressed while they were taking abiraterone. During the trial, all of the men took enzalutamide (standard-of-care therapy) once a day. However, some of the men also had up to 4 doses (8 weeks apart) of I-131-1095 (in addition to taking enzalutamide once a day). At specified times during the trial, all of the men had blood tests (to measure levels of prostate-specific antigen \[PSA\]) and imaging studies (to assess tumor status). The two groups of men were then compared in several ways. The main comparison was the percentage of men in each group with at least a 50% decrease in PSA levels. Other comparisons involved the response of the tumors (as seen on imaging) and overall survival. To assess safety, the number of adverse events in both groups were also compared.

Sponsor

Progenics Pharmaceuticals

Phase

Phase 2

Contacts

Jean-Claude Provost, MD (STUDY_DIRECTOR)

ClinicalTrials.gov

NCT03939689

Drug / Compound

DCFPyL

Isotope(s):
Target(s):
  • PSMA
Ligand Class: Small Molecules

Eligibility

Inclusion

  • Poor performance status
  • Disease progression on prior abiraterone therapy as defined by meeting at least one of the following criteria per the investigator:
  • If sexually active, agree to use a medically acceptable method of birth control or sexual abstinence from the time of dosing through 28 days after the last dose of I-131-1095. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent.
  • ECOG performance status 0-2
  • Soft tissue disease progression defined by RECIST 1.1
  • Subjects receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks prior to Randomization
  • Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features at initial diagnosis
  • Other serious medical conditions such as symptomatic peripheral neuropathy CTCAE Grade 2 or higher; or clinically significant cardiovascular disease per the Investigator or treating physician
  • Estimated life expectancy of at least 6 months as determined by the Investigator.
  • Bone disease progression defined by two or more new lesions on bone scan
  • PSA progression as defined by a minimum of two rising PSA levels at least 1 week apart
  • Prior intolerance to cytotoxic agents
  • Subjects who are ineligible or choose not to receive taxane-based chemotherapy based on personal preference or physician opinion. Examples of conditions that could make a patient ineligible or refuse to receive taxane-based chemotherapy, but would allow them to still be eligible to receive I-131-1095 include the following:
  • Radiographic evidence of metastatic disease prior to Randomization or up to 21 days prior to Screening
  • Planned to receive treatment with enzalutamide
  • Castration-resistant prostate cancer, with serum testosterone ≤ 50 ng/dL at Screening
  • History of another malignancy suspected for recurrence or metastases

Exclusion

  • Prior PSMA-targeted radioligand therapy
  • Total bilirubin \> 2 x ULN unless in instances of known or suspected Gilbert's disease
  • Treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 within 6 months prior to Randomization
  • Previous use of enzalutamide for more than 7 days prior to consent
  • Subjects with any medical condition or other circumstances that, in the opinion of the investigator, compromise obtaining reliable data, achieving study objectives, or completing the study.
  • AST or ALT \> 2.5 x ULN
  • Albumin \< 3.0 g/dL (30 g/L)
  • Active malignancy other than prostate cancer, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or non-muscle invasive bladder/urothelial cancer
  • Platelet count \< 100,000/μL
  • Superscan as evidenced on baseline bone scan
  • Received any anti-tumor therapy within 4 weeks of Randomization, with the exception of abiraterone, GnRH therapy and non-radioactive bone-targeted agents
  • Impaired organ function as evidenced by the following laboratory values at Screening:
  • Planned initiation of alternative therapy for prostate cancer, investigational therapy, or participation in clinical trials during the study
  • Received prior chemotherapy for castration-resistant prostate cancer
  • Major surgery within 4 weeks of Randomization
  • QT interval corrected for heart rate (QTc) \> 470 msec
  • Known or suspected brain metastasis or active leptomeningeal disease
  • History or risk of seizure (i.e., clinically significant neurological disorder) or any other condition that contraindicates treatment with enzalutamide
  • Calculated creatinine clearance (CrCL) \< 30 mL/min (Cockroft-Gault equation), or currently on renal dialysis.
  • Absolute neutrophil count \< 1500 μL
  • Prior hemi-body irradiation
  • Hemoglobin \< 9.5 g/dL
  • Gastrointestinal disorder affecting absorption of oral medications