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

NCT03545165 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 1802018988
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (3)

• Number of Patients With Dose Limiting Toxicity (DLT) of Combination Therapy in a 2-Week Dose-Fractionation Regimen

  Dose limiting toxicity of combination therapy was determined by monitoring for adverse events following therapy

  Approximately 3 months after enrollment

• Cumulative Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D) of Combination Therapy in a 2-Week Dose-Fractionation Regimen

  Cumulative maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of combination therapy was determined by monitoring dose-limiting toxicity and adverse events in the dosing or treatment cohorts

  Approximately 3 months after enrollment

• The Proportion With PSA Decline Following the Dose-Fractionated Combination Therapy by Comparing the Change in PSA Levels After Therapy to the Baseline, Pre-Treatment PSA.

  The proportion of patients with PSA decline following treatment with the combination of 177Lu-J591 and 177Lu-PSMA-617 was determined by comparing PSA levels prior to and following radionuclide therapy

  At baseline and at 2 weeks on therapy

Secondary Outcomes (7)

• Number of Subjects With Radiographic Response by RECIST 1.1 With Prostate Cancer Working Group 3 (PCWG3) Modifications

  At the efficacy (scan) visit time point (12 weeks)

• Biochemical Progression-Free Survival by PCWG3 Criteria

  Through study completion, up to 26 months

• Radiographic Progression-Free Survival by PCWG3 Criteria

  Through study completion, up to 26 months

• Overall Survival Following Treatment With the Combination of 177Lu-J591 and 177Lu-PSMA-617 in a 2-Week Dose-Fractionation Regimen

  Through study completion, up to 26 months

• Changes in CTC Count as Measured by CellSearch

  At the efficacy (scan) visit time point (12 weeks)

Other Outcomes (2)

• Disease Assessment With PSMA-Ligand Based Imaging Prior to and Following Investigational Treatment

  Up to 12 weeks

• Radiation Dosimetry of Combination Therapy

  Up to 12 weeks

Study Arms (1)

All Subjects

EXPERIMENTAL

177Lu-PSMA-617 \[1.85 GBq (50 mCi) - 9.25 GBq (250 mCi)\] x2 doses, 2 weeks apart (Treatment Visit #1 and #2), IV administration 177Lu-J591 \[1.35 GBq/m2 or 36.5 mCi/m2\] x2 doses, 2 weeks apart (Treatment Visit #1 and #2), IV administration 68Ga-PSMA-HBED-CC \[185 ±74 MBq or 5 ±2 mCi\] intravenous during screening and at 12 weeks (±1 week) with standard imaging

Drug: 177Lu-PSMA-617; Drug: 177Lu-J591; Drug: 68Ga-PSMA-HBED-CC

Interventions

177Lu-PSMA-617 DRUG

\[1.85 GBq (50 mCi) - 9.25 GBq (250 mCi)\]

All Subjects

177Lu-J591 DRUG

\[1.35 GBq/m2 or 36.5 mCi/m2\]

All Subjects

68Ga-PSMA-HBED-CC DRUG

\[185 ±74MBq or 5 ±2 mCi\]

All Subjects

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Subjects who have documented progressive metastatic CRPC disease, who meet the inclusion and exclusion criteria will be eligible for participation in this study.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of prostate
• 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
• ECOG performance status of 0-2
• 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.
• Have previously been treated with at least one of the following:
• Androgen receptor signaling inhibitor (such as enzalutamide)
• CYP 17 inhibitor (such as abiraterone acetate)
• Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.
• Age \> 18 years
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count \>2,000 cells/mm3
• Hemoglobin ≥9 g/dL
• Platelet count \>150,000 x 109/L
• Serum creatinine \<1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault

You may not qualify if:

• Implantation of investigational medical device ≤4 weeks of Treatment visit #1 (Day 1) or current enrollment in oncologic investigational drug or device study
• 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
• Prior systemic beta-emitting bone-seeking radioisotopes
• Known active brain metastases or leptomeningeal disease
• History of deep vein thrombosis and/or pulmonary embolus within 1 month of Treatment visit #1
• 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
• Radiation therapy for treatment of PC ≤4 weeks of Treatment visit #1
• 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.
• 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
• Currently active other malignancy other than non-melanoma skin cancer. Patients are considered not to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse.
• Known history of known myelodysplastic syndrome

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Related Publications (1)

• Vlachostergios PJ, Niaz MJ, Skafida M, Mosallaie SA, Thomas C, Christos PJ, Osborne JR, Molina AM, Nanus DM, Bander NH, Tagawa ST. Imaging expression of prostate-specific membrane antigen and response to PSMA-targeted beta-emitting radionuclide therapies in metastatic castration-resistant prostate cancer. Prostate. 2021 Apr;81(5):279-285. doi: 10.1002/pros.24104. Epub 2021 Jan 19.

  PMID: 33465252 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Pluvicto; gallium 68 PSMA-11

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Limitations and Caveats

The study was terminated early due to sponsor withdrawal (PSMA-617 no longer available for purchase).

Results Point of Contact

• Title: Scott Tagawa MD, Principal Investigator
• Organization: Weill Cornell Medicine

guonc@med.cornell.edu

646-962-2072

Study Officials

• Scott Tagawa, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2018
• First Posted: June 4, 2018
• Study Start: April 18, 2018
• Primary Completion: July 15, 2020
• Study Completion: July 15, 2020
• Last Updated: August 24, 2021
• Results First Posted: August 24, 2021

Record last verified: 2021-07

Locations

US (1)