Clinical Trials /

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

NCT03490838

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 177Lu-PSMA-R2 in Patients With PSMA Positive Progressive, Metastatic, Castration Resistant Prostate Cancer
  • Official Title: A Phase 1/2 Open-label, Multi-center, Dose-escalation Study of Safety, Tolerability, Pharmacokinetics, Dosimetry, and Response to Repeat Dosing of 177Lu-PSMA-R2 Radio-ligand Therapy in Patients With Prostate Specific Membrane Antigen (PSMA) Positive (68Ga-PSMA-R2) Progressive Metastatic Castration-resistant Prostate Cancer, Following Previous Systemic Treatment

Clinical Trial IDs

  • ORG STUDY ID: A206T-G01-001
  • NCT ID: NCT03490838

Conditions

  • Prostatic Neoplasm

Interventions

DrugSynonymsArms
177Lu-PSMA-R2Phase I: Dose Escalation Cohort 1

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase I: Dose Escalation Cohort 1Experimental3.70 GBq (100 mCi) x 3 times = 11.10 GBq
  • 177Lu-PSMA-R2
Phase I: Dose Escalation Cohort 2Experimental7.40 GBq (200 mCi) x 3 times = 22.2 GBq
  • 177Lu-PSMA-R2
Phase I: Dose Escalation Cohort 3Experimental9.25 GBq (250 mCi) x 3 times = 27.75 GBq
  • 177Lu-PSMA-R2
Phase II: Dose Expansion CohortExperimentalDose to be chosen from Phase I
  • 177Lu-PSMA-R2

Eligibility Criteria

        Inclusion Criteria:

          -  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/L 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 disease progression on or after prior systemic treatment administered for
             the advanced disease including CYP 17 inhibitors and/or androgen-pathway inhibitors
             (i.e. abiraterone and/or enzalutamide when available) and no more than one line of
             chemotherapy for the advanced disease, or patients who were ineligible (unfit) to
             receive chemotherapy. Disease progression defined as increasing serum PSA (per PCWG3),
             radiological progression or ≥ 2 new bone lesions. (Chemical castration is required
             unless surgically orchiectomized.)

          -  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 4.03 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

               1. Platelet count of >100 x109/L

               2. White blood cell (WBC) count 3,000/mL

               3. Neutrophil count of > 1,500/mL

               4. Hemoglobin ≥ 10 g/dL

               5. Serum creatinine < 1.5 x upper limit normal (ULN) or estimated glomerular
                  filtration rate (GFR) > 50 mL/min based upon Chronic Kidney Disease-Epidemiology
                  Collaboration (CKD-EPI) equation. Patients with estimated GFR between 50 - 60
                  mL/min at baseline will require a 99mTc-DTPA GFR test and only patients with
                  non-obstructive pathology will be included in the study.

               6. Total bilirubin < 3 x ULN (except if confirmed history of Gilbert's disease)

               7. Baseline serum albumin > 30 g/L

               8. Aspartate aminotransferase (AST) < 3 times the ULN

          -  For male patients with partners of childbearing potential, agreement to use barrier
             contraceptive method (condom) and to continue its use for 6 months from receiving the
             last dose of IP

        Exclusion Criteria:

          -  Pathological finding consistent with small cell, neuroendocrine carcinoma of the
             prostate or any other histology different than adenocarcinoma

          -  Previously administered chemotherapy or 223Ra-therapy within the context of diffuse
             bone or 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)

          -  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 relevant 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 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

          -  Active infection including human immunodeficiency virus (HIV) and untreated hepatitis
             B, and hepatitis C. Screening for chronic conditions is not required.

          -  Patients who have received any investigational treatment agent within the last 28
             days.

          -  Known allergies, hypersensitivity, or intolerance to the IP or its excipients

          -  Known history of myelodysplastic syndrome/leukemia at any time

          -  Patient is unlikely to comply with study procedures, restrictions and requirements and
             judged by the Investigator that the patient is not suitable for participation in the
             study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame:dosing through 5-years post-treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Phase 1: PSA response
Time Frame:weeks 7, 13, and 19 and up to 5 years post-treatment
Safety Issue:
Description:
Measure:Phase 1: Time to PSA progression
Time Frame:5 years post-treatment
Safety Issue:
Description:
Measure:Phase 1: rPFS per PCWG3
Time Frame:5 years post-treatment
Safety Issue:
Description:
Measure:Phase 1: Overall Survival (OS)
Time Frame:5 years post-treatment
Safety Issue:
Description:
Measure:Phase 2: Treatment-Emergent Adverse Events
Time Frame:dosing up to 5 years post-treatment
Safety Issue:
Description:
Measure:Phase 2: PSA response
Time Frame:weeks 7, 13, 19 and up to 5 years post-treatment
Safety Issue:
Description:
Measure:Phase 2: Time to PSA progression
Time Frame:5 years post-treatment
Safety Issue:
Description:
Measure:Phase 2: Overall Survival
Time Frame:5 years post-treatment
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Advanced Accelerator Applications

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