Clinical trial NCT04291300: Lutetium-177-PSMA Radioligand Therapy in Advanced Salivary Gland Cancer Patients
Official title: Lutetium-177-PSMA Radioligand Therapy for Advanced Salivary Gland Cancer, a Phase II Pilot Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Salivary Gland Cancer
Salivary Duct Carcinoma
Adenoid Cystic Carcinoma
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Dutch Cancer Society
First posted: 2020-03-02
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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
Primary purpose: TREATMENT

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

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.

Eligibility 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

Primary outcomes:
measure: Adverse events measured using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
timeFrame: Through study completion, up until 3 years after last patient commences treatment
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Through study completion, up until 3 years after last patient commences treatment
measure: Progression free survival (PFS)
timeFrame: Through study completion, up until 3 years after last patient commences treatment
measure: Overall survival (OS)
timeFrame: Through study completion, up until 3 years after last patient commences treatment
measure: Duration of response (DoR)
timeFrame: Through study completion, up until 3 years after last patient commences treatment
measure: Quality of life (QoL)
timeFrame: Trough study completion, up until 3 years after last patient commences treatment
measure: Quality of life (QoL)
timeFrame: Trough study completion, up until 3 years after last patient commences treatment
measure: Quality of life (QoL)
timeFrame: Trough study completion, up until 3 years after last patient commences treatment
measure: Quality of life (QoL)
timeFrame: Trough study completion, up until 3 years after last patient commences treatment
measure: Dosimetry
timeFrame: From start of study till last patient commences last SPECT/CT (7 days after first treatment cycle)
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
Study officials:
References: