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

• ClinicalTrials.gov Identifier: NCT04291300
• Recruitment Status: Recruiting
• First Posted: March 2, 2020
• Last Update Posted: October 28, 2022
• Sponsor: Radboud University Medical Center
• Collaborator: Dutch Cancer Society
• Information provided by (Responsible Party): Radboud University Medical Center

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Salivary Gland Cancer; Salivary Duct Carcinoma; Adenoid Cystic Carcinoma	Drug: Lutetium-177-PSMA-I&T	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Phase II pilot study, single centre, two cohorts. Cohort 1: Patients with R/M ACC, Cohort 2: Patients with R/M SDC
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Lutetium-177-PSMA Radioligand Therapy for Advanced Salivary Gland Cancer, a Phase II Pilot Study.
• Actual Study Start Date: May 26, 2020
• Estimated Primary Completion Date: May 26, 2023
• Estimated Study Completion Date: May 1, 2025

Arms and Interventions

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 Name: Lutetium-177 Prostate Specific Membrane Antigen

Outcome Measures

Primary Outcome Measures :

1. Adverse events measured using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Through study completion, up until 3 years after last patient commences treatment ]
   Safety

Secondary Outcome Measures :

1. Objective response rate (ORR) [ Time Frame: Through study completion, up until 3 years after last patient commences treatment ]
   Response will be measured according to RECIST version 1.1
2. Progression free survival (PFS) [ Time Frame: Through study completion, up until 3 years after last patient commences treatment ]
   PFS will be defined as time from study enrollment until disease progression or death.
3. Overall survival (OS) [ Time Frame: Through study completion, up until 3 years after last patient commences treatment ]
   OS will be defined as time from study enrollment until date of death of any cause.
4. Duration of response (DoR) [ Time Frame: Through study completion, up until 3 years after last patient commences treatment ]
   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
5. Quality of life (QoL) [ Time Frame: Trough study completion, up until 3 years after last patient commences treatment ]
   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.
6. Quality of life (QoL) [ Time Frame: Trough study completion, up until 3 years after last patient commences treatment ]
   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.
7. Quality of life (QoL) [ Time Frame: Trough study completion, up until 3 years after last patient commences treatment ]
   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.
8. Quality of life (QoL) [ Time Frame: Trough study completion, up until 3 years after last patient commences treatment ]
   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.
9. Dosimetry [ Time Frame: From start of study till last patient commences last SPECT/CT (7 days after first treatment cycle) ]
   Delivered doses will be calculated based on pharmacokinetics in the blood and dosimetry on SPECT/CT imaging.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Netherlands

Radboudumc; Recruiting

Nijmegen, Gelderland, Netherlands, 6500HB

Contact: Carla ML van Herpen, MD, PhD +31243613457 Carla.vanHerpen@radboudumc.nl

Principal Investigator: Carla ML van Herpen, MD, PhD

Sub-Investigator: Martin Gotthardt, MD, PhD

Sub-Investigator: James Nagarajah, MD, PhD

Sub-Investigator: Maike JM Uijen, MD

Sponsors and Collaborators

Radboud University Medical Center

Dutch Cancer Society

More Information

• Responsible Party: Radboud University Medical Center
• ClinicalTrials.gov Identifier: NCT04291300
• Other Study ID Numbers: MOHN18
• First Posted: March 2, 2020
• Last Update Posted: October 28, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Salivary Gland Neoplasms; Carcinoma, Adenoid Cystic; Carcinoma, Ductal; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases; Adenocarcinoma; Neoplasms, Ductal, Lobular, and Medullary