Clinical Trial · NCT03545165

177Lu-J591 and 177Lu-PSMA-617 Combination for mCRPC

Overview

Phase I dose escalation study with combination of 177Lu-J591 and 177Lu-PSMA-617 using a dose-fractionated regimen will be performed in patients with documented progressive metastatic CRPC. The cumulative 177Lu-J591 dose for each subject will be 2.7 GBq/m2 (73 mCi/m2) of 177Lu with 20 mg J591 and the cumulative 177Lu-PSMA-617 dose for each subject will vary (depending on the Cohort) from 3.7 GBq (100 mCi) to 18.5 GBq (500 mCi). The 177Lu-PSMA-617 dose will be escalated in up to 6 different dose levels (3+3 dose-escalation study / de-escalation design). For the phase II portion, a minimum number of 14 patients will be enrolled at MTD (including those enrolled at MTD in Phase I) and a maximum of 24.

Sponsor

Weill Medical College of Cornell University

Phase

Phase 1/2

Contacts

Scott Tagawa, MD (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT03545165

Drug / Compound

PSMA-617

Isotope(s):

Target(s):

PSMA

Ligand Class: Small Molecules

Chelator: DOTA

J591

Isotope(s):

Target(s):

PSMA

Ligand Class: Antibodies

Chelator: DOTA

Eligibility

Inclusion

Patients must have normal organ and marrow function as defined below:
Serum AST and ALT\<1.5 x ULN in the absence of liver metastases; \<3 x ULN if due to liver metastases (in both circumstances bilirubin must meet entry criteria)
Radiation therapy for treatment of PC ≤4 weeks of Treatment visit #1
CYP 17 inhibitor (such as abiraterone acetate)
Use of investigational drugs ≤4 weeks or \<5 half-lives of Treatment visit # 1(Day 1) or current enrollment in investigational oncology drug or device study
Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.
Serum total bilirubin\<1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin must be normal)
Serum creatinine \<1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault
Have previously been treated with at least one of the following:
Histologically or cytologically confirmed adenocarcinoma of prostate
Hemoglobin ≥9 g/dL
Having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principle investigator and chairperson during the study and for 1 month after last study drug administration
Inclusion Criteria
Prior systemic beta-emitting bone-seeking radioisotopes
Implantation of investigational medical device ≤4 weeks of Treatment visit #1 (Day 1) or current enrollment in oncologic investigational drug or device study
Platelet count \>150,000 x 109/L
Absolute neutrophil count \>2,000 cells/mm3
Known history of known myelodysplastic syndrome
Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
Known active brain metastases or leptomeningeal disease
Patients on stable dose of bisphosphonates or denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication, however patients are not allowed to initiate bisphosphonate/Denosumab therapy during the DLT-assessment period of the study.
History of deep vein thrombosis and/or pulmonary embolus within 1 month of Treatment visit #1
Have serum testosterone \< 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone bilateral orchiectomy.
Androgen receptor signaling inhibitor (such as enzalutamide)
ECOG performance status of 0-2
Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria: i. PSA progression ii. Objective radiographic progression in soft tissue iii. New bone lesions

Exclusion

Exclusion criteria not yet provided.