177Lu-PSMA-R2 in Patients With PSMA Positive Progressive, Metastatic, Castration Resistant Prostate Cancer

NCT03490838 | Terminated Phase 1 FDA Drug

• 3 other identifiers: A206T-G01-0012017-004034-29CAAA602A12101
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 11

Brief Summary

This Phase 1/2 study is intended to investigate the safety, tolerability, and radiation dosimetry of 177Lu-PSMA-R2 and further assess preliminary efficacy data in patients with metastatic castration-resistant prostate cancer (mCRPC). The Phase 1 portion of the study will determine the recommended dose of 177Lu-PSMA-R2 for radio-ligand therapy (RLT) of mCRPC, and the Phase 2 portion will expand into approximately 60 patients documenting the preliminary activity (anti-tumor response) of repeated treatments administered, continuing safety assessments and collecting QoL data.

Conditions

Prostatic Neoplasm

Keywords

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Cancer of Prostate; Cancer of the Prostate; Neoplasms, Prostate; Neoplasms, Prostatic; Prostate Cancer; Prostate Neoplasms; Prostatic Cancer; Prostate-Specific Membrane Antigen; PSMA; PSMA radioligand therapy

Outcome Measures

Primary Outcomes (2)

• Phase I: Incidence of dose limiting toxicities (DLTs) during first cycle of study treatment.

  A dose-limiting toxicity (DLT) is defined as any toxicity not attributable to the disease or disease-related processes under investigation, the time window for DLT assessment period is Cycle 1. To be considered a DLT, it must be related to the IP (attributions: possible, probable, and definite) while fulfilling one of the following criteria as per the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.

  Up to 8 weeks after the first 177Lu-PSMA-R2 dose

• Phase II: Prostate-Specific Antigen (PSA) response rate 50

  PSA response rate 50 is defined as the proportion of participants who have a greater or equal 50% in PSA from Baseline that is confirmed by a second PSA measurement 4 weeks later, as per Prostate Cancer Working Group 3 (PCWG3) criteria.

  Week 13 (12 weeks after the first 177Lu-PSMA-R2 injection)

Secondary Outcomes (19)

• Phase I and II: Treatment Emergent Adverse Event (TEAE) rate

  From randomization till 30 days safety follow-up, assessed up to 4 years (estimated final OS analysis)

• Phase I and II: Objective Response Rate (ORR)

  From date of randomization assessed up to 4 years (estimated final OS analysis)

• Phase I and II: Duration of Response (DoR)

  From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to 4 years (estimated final OS analysis)

• Phase I and II: Prostate-Specific Antigen (PSA) response rate 30

  Week 13 (12 weeks after the first 177Lu-PSMA-R2 injection)

• Phase I: Prostate-Specific Antigen (PSA) response rate 50

  Week 13 (12 weeks after the first 177Lu-PSMA-R2 injection)

Study Arms (6)

Phase I: Dose Escalation Cohort 1

EXPERIMENTAL

3.70 GBq (100 mCi) x 3 times

Drug: 177Lu-PSMA-R2

Phase I: Dose Escalation Cohort 2

EXPERIMENTAL

7.40 GBq (200 mCi) up to 4 times

Drug: 177Lu-PSMA-R2

Phase I: Dose Escalation Cohort 3

EXPERIMENTAL

11.1 GBq (300 mCi) up to 4 times

Drug: 177Lu-PSMA-R2

Phase I: Dose Escalation Cohort 4

EXPERIMENTAL

14.8 GBq (400 mCi) up to 4 times

Drug: 177Lu-PSMA-R2

Phase I: Dose Escalation Cohort 5

EXPERIMENTAL

18.5 GBq (500 mCi) up to 4 times

Drug: 177Lu-PSMA-R2

Phase I: Dose Escalation Cohort 6

EXPERIMENTAL

18.5 GBq (500 mCi) up to 3 times

Drug: 177Lu-PSMA-R2

Interventions

177Lu-PSMA-R2 DRUG

radio-ligand therapy

Phase I: Dose Escalation Cohort 1; Phase I: Dose Escalation Cohort 2; Phase I: Dose Escalation Cohort 3; Phase I: Dose Escalation Cohort 4; Phase I: Dose Escalation Cohort 5; Phase I: Dose Escalation Cohort 6

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male patients, 18 years of age or older
• Signed and dated written ICF by the patient or legally acceptable representative prior to any study-specific procedures
• Histologically confirmed adenocarcinoma of the prostate
• Serum testosterone levels \< 50 ng/dL after surgical or continued chemical castration
• Metastatic disease documented by CT/MRI or bone scan (not older than 28 days at enrollment) revealing at least one metastatic lymph-node, visceral metastasis and/or bone metastasis
• Positive 68Ga-PSMA-R2 PET/CT scan for central eligibility assessment. Patients who receive 68Ga-PSMA-R2 as part of separate clinical protocol are eligible (must meet all study eligibility criteria)
• Documented progressive mCRPC on or after the last systemic treatment administered for the advanced disease including metastatic disease. Disease progression defined as increasing serum PSA (per PCWG3), radiological progression or ≥ 2 new bone lesions.
• Must have received prior systemic treatment for mCRPC including CYP17 inhibitors and/or androgen-pathway inhibitors (i.e. abiraterone and/or enzalutamide when available) and one and no more than one line of chemotherapy for the advanced disease (unless ineligible (unfit) to receive chemotherapy).
• At least 28 days elapsed between last anti-cancer treatment administration and the initiation of study treatment (except for Luteinizing Hormone-releasing Hormone \[LHRH\] or Gonadotropin-releasing Hormone \[GnRH\]), or resolution of all previous treatment related toxicities to CTCAE version 5.0 grade of ≤ 1 (except for chemotherapy induced alopecia and grade 2 peripheral neuropathy or grade 2 urinary frequency which are allowed). Prior major surgery must be at least 12 weeks prior to study entry.
• Eastern cooperative oncology group (ECOG) performance status of 0-2 with a life expectancy ≥ 6 months
• Adequate bone marrow reserve and organ function as demonstrated by complete blood count, and biochemistry in blood and urine at baseline
• Platelet count of \>100 x10e9/L
• White blood cell (WBC) count \> 3,000/mL
• Neutrophil count \> 1,500/mL
• Hemoglobin ≥ 10 g/dL

You may not qualify if:

• Pathological finding consistent with small cell, neuroendocrine carcinoma of the prostate or any other histology different than adenocarcinoma.
• Diffuse bone-marrow involvement (i.e. "superscan" defined as bone scintigraphy in which there is excessive skeletal radioisotope uptake \[\>20 bone lesions\] in relation to soft tissues along with absent or faint activity in the genitourinary tract due to diffuse bone/ bone marrow metastases)
• Prior exposure to radioligand therapy radioisotope therapy (e.g. 89Sr), systemic radiotherapy or 223Ra-therapy.
• Current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, any level of urinary obstruction requiring indwelling/condom catheters
• Spinal cord compression or brain metastases
• Uncontrolled pain that results in patient's lack of compliance with the imaging procedures
• Uncontrolled cardiovascular history, defined as:
• Congestive heart failure (New York Heart Association \[NYHA\] II, III, IV)
• Mean resting corrected QT interval (QTc) \>450 millisecond (msec), obtained from 3 ECGs recordings, using the screening clinic ECG machine-derived QTc value.
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval \>250 msec).
• Any factor increasing the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives, or any concomitant medication known to prolong the QT interval.
• Other known co-existing malignancies except non-melanoma skin cancer or low grade superficial bladder cancer unless definitively treated and proven no evidence of recurrence for 5 years.
• History of deep vein thrombosis and/or pulmonary embolism within 4 weeks of enrollment.
• Known incompatibility to CT or PET scans.
• Any evidence of severe or uncontrolled systemic or psychiatric diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol

Sponsors & Collaborators

• Advanced Accelerator Applications: lead

Study Sites (11)

Pheonix Molecular Imaging Center

Phoenix, Arizona, 85040, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Yale New Haven Children Hospital

New Haven, Connecticut, 06520, United States

Location

Tulane Cancer Center Tulance Cancer

New Orleans, Louisiana, 70112, United States

Location

John Hopkins University - Kimmel Comp. Cancer Center

Baltimore, Maryland, 21231, United States

Location

National Institute of Health

Bethesda, Maryland, 20892, United States

Location

Mount Sinai Hospital School of Medicine

New York, New York, 10029, United States

Location

University of Wisconsin / Paul P. Carbone Comp Cancer Center

Madison, Wisconsin, 53792, United States

Location

Hospital Vall Hebrón

Barcelona, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Related Links

• Novartis Clinical Trial Results

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2018
• First Posted: April 6, 2018
• Study Start: May 24, 2018
• Primary Completion: May 26, 2021
• Study Completion: June 2, 2022
• Last Updated: May 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); ES (2)