Lutetium-177-PSMA Radioligand Therapy in Advanced Salivary Gland Cancer Patients (LUPSA)

Lutetium-177-PSMA Radioligand Therapy for Advanced Salivary Gland Cancer, a Phase II Pilot Study.

Phase 2 pilot study, which evaluates the safety and efficacy of Lutetium-177-PSMA radioligand therapy in advanced salivary gland cancer patients.

Study Overview

• Status: Completed
• Conditions: Adenoid Cystic Carcinoma; Salivary Gland Cancer; Salivary Duct Carcinoma
• Intervention / Treatment: Drug: Lutetium-177-PSMA-I&T

Detailed Description

Rationale: Prostate specific membrane antigen (PSMA) is a transmembrane protein, which is expressed on prostate cancers cells and other malignancies. Recently, several ligands have been developed that target PSMA. Linked to Gallium-68, this enables diagnostic 68Ga-PSMA-PET/CT scans. Linked to Lutetium-177 enables therapeutic 177Lu-PSMA Radioligand therapy. Most research on the diagnostic and therapeutic possibilities of PSMA has been conducted in patients with advanced prostate cancer.

This research group investigates whether these findings also apply to salivary gland cancer (SGC), a rare cancer. Previously the investigators conducted a phase II 68Ga-PSMA imaging study (NCT03319641), to evaluate PSMA ligand uptake in locally advanced, recurrent and metastatic (R/M) ACC and SDC (two subtypes of SGC). A relevant PSMA-ligand uptake was observed in 93% of ACC patients and 40% of SDC patients. Therefore we consider 177Lu-PSMA radioligand therapy a potential new treatment option for these subtypes of SGC.

Objective: To evaluate the safety and efficacy of 177Lu-PSMA RLT in patients with R/M ACC and SDC with PSMA ligand uptake.

Study design: Phase II pilot study, single centre, two cohorts.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500HB
      • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have the ability to provide written informed consent.
• Patients must be ≥ 18 years of age.
• Patients must have an ECOG performance status of 0 to 2.
• Patients must have histological, pathological, and/or cytological confirmation of either adenoid cystic carcinoma or salivary duct carcinoma.
• Patients must have incurable, local or regional recurrent or metastatic ACC or SDC.
• Patients with ACC can only participate in case of objective growth in the last three months or complaints due to the disease.

• Patients must have adequate organ function:

  • Sufficient bone marrow capacity as defined by: WBC count (white blood cell) ≥2.5x10^9/L, PLT (platelet) count ≥100x10^9/L, Hb ≥6 mmol/L, absolute neutrophil count (ANC) ≥1.5x10^9/L
  • Adequate liver function as defined by:Total bilirubin ≤1.5 x ULN. For patients known with Gilbert's Syndrome ≤ 3 x ULN is permitted. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 × ULN OR ≤5.0 × ULN for patients with liver metastases.
  • Adequate kidney function as defined by:serum creatinine ≤1.5 x ULN or creatinine clearance ≥ 50 mL/min
• Patients must have measurable disease at baseline. Defined as ≥ 1 lesion ≥ 2 cm (long axis) that is present on baseline CT.
• Patients must have a positive 68Ga-PSMA PET/CT scan, defined by at least one lesion ≥ 1.5 cm (long axis) with a ligand uptake above liver level.

Exclusion Criteria:

• Patients whom are pregnant or breast feeding.
• Patients with reproductive potential not implementing adequate contraceptives measures.
• Patients with known brain metastases or cranial epidural disease or intracardial metastases.
• Patients with concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.
• Patients with urinary tract obstruction or marked hydronephrosis
• Less than 4 weeks since last myelosuppressive therapy or other radionuclide therapy.
• Concomitant cancer treatments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lutetium treatment; Drug: Lutetium-177-PSMA-I&T, 4 cycles of 7.4 GBq intravenously, every 6 weeks.	Drug: Lutetium-177-PSMA-I&T; 4 cycles of 7.4 GBq 177Lu-PSMA every 6 weeks.; Other Names: Lutetium-177 Prostate Specific Membrane Antigen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events measured using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Safety	Through study completion, up until 3 years after last patient commences treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Response will be measured according to RECIST version 1.1	Through study completion, up until 3 years after last patient commences treatment
Progression free survival (PFS)	PFS will be defined as time from study enrollment until disease progression or death.	Through study completion, up until 3 years after last patient commences treatment
Overall survival (OS)	OS will be defined as time from study enrollment until date of death of any cause.	Through study completion, up until 3 years after last patient commences treatment
Duration of response (DoR)	Only patients with complete remission or partial response will be included in the assessment of DoR. DoR is defined as time from study enrollment until disease progression or death	Through study completion, up until 3 years after last patient commences treatment
Quality of life (QoL)	QoL will be assessed using EORTC QLQ-C30 questionnaire. This is the core questionnaire for assessing health related quality of life of cancer patients participating in clinical trials. It contains 30 items and incorporates a global health status scale, five functional scales, three symptom scales, and several single items assessing additional symptoms. All of the scales and single-item measures range from 0-100. A high score for global health status represents a high QoL, a high score in functional scale represents a high/healthy level of functioning, a high score for a symptom scale/item represents a high level of symptomatology/problems.	Trough study completion, up until 3 years after last patient commences treatment
Quality of life (QoL)	QoL will be assessed using EORTC QLQ-H&N43 questionnaire. This is an additional questionnaire to assess health related topics relevant for head and neck cancer patients. The module contains 43 questions, all symtom scales or symptom items.All of the scale/item measures range from 0-100. For all scales/items higher scores indicate more problems.	Trough study completion, up until 3 years after last patient commences treatment
Quality of life (QoL)	QoL will be assessed using performance status scale for head&neck cancer patients (PSS-HN). It contains 3 items, each randing from 0-100. These items are rated by the health professional. A high score indicates a high performance status.	Trough study completion, up until 3 years after last patient commences treatment
Quality of life (QoL)	QoL will be assessed using pain visual analogue scale (VAS) questionnaire. This include two questions: the average pain during the past week and the worst pain during the past week. Both questions range from 0-100, a higher score indicates more pain.	Trough study completion, up until 3 years after last patient commences treatment
Dosimetry	Delivered doses will be calculated based on pharmacokinetics in the blood and dosimetry on SPECT/CT imaging.	From start of study till last patient commences last SPECT/CT (7 days after first treatment cycle)

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Dutch Cancer Society

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2020
• Primary Completion (Actual): February 13, 2023
• Study Completion (Actual): February 13, 2023

Study Registration Dates

• First Submitted: February 28, 2020
• First Submitted That Met QC Criteria: February 28, 2020
• First Posted (Actual): March 2, 2020

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Salivary Gland Diseases; Mouth Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma; Carcinoma, Adenoid Cystic; Salivary Gland Neoplasms; Carcinoma, Ductal
• Other Study ID Numbers: MOHN18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No