Clinical trial NCT06125028: [68Ga]Ga-PentixaFor-PET Imaging for Staging of Marginal Zone Lymphoma
Official title: A Pivotal Phase 3 Clinical Trial to Assess the Diagnostic Performance and Safety of [68Ga]Ga-PentixaFor ([68Ga]Ga-PTF), a Positron Emission Tomography (PET) Imaging Agent, Versus [18F]FDG PET/CT Imaging, for Staging of Patients With Confirmed Marginal Zone Lymphoma Exemplary for CXCR4-positive Malignant Lymphomas: a Prospective, International, Multi-center, Comparative, Randomized, Cross-over, Open-label Lymphoma Diagnostic Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Marginal Zone Lymphoma
Lead sponsor: Pentixapharm AG
Sponsor class: INDUSTRY
Collaborators: name: Pivotal S.L.
First posted: 2023-11-09
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: This will be a pivotal prospective prospective, international, multi-center, comparative, randomized, cross-over, open-label lymphoma diagnostic trial to assess the diagnostic performance and safety of the positron emission tomography (PET) imaging agent \[68Ga\]Ga-PTF) , versus \[18F\]FDG PET/CT imaging, for staging of patients with confirmed marginal zone lymphoma exemplary for CXCR4-positive malignant lymphomas.


Eligibility criteria: Inclusion criteria:

All patients must meet all of the following criteria:

1. Signed informed consent from the patient.
2. Patients of either gender, aged ≥ 18 years.
3. Patients with a histologically proven diagnosis of marginal zone lymphoma (MZL) according to the World Health Organization (WHO) classification of lymphoid neoplasms. Patients must have a biopsy-proven nodal, extranodal, or splenic MZL (at the time of enrolment, the CXCR4 expression status will be unknown).
4. Treatment-naïve.
5. Negative pregnancy test in women capable of child-bearing and their agreement to use highly effective contraception for 1 month after the last dose of \[68Ga\]Ga-PTF and \[18F\]FDG.
6. For male patients whose partner is of child-bearing potential: The patient is willing to ensure that he and his partner use effective contraception for 1 month after the last dose of \[68Ga\]Ga-PTF and \[18F\]FDG.
7. Acceptable organ function, as evidenced by the following laboratory data:

   1. No renal impairment: Estimated glomerular filtration rate (eGFR) \> 30 mL/min/1.73 m2or creatinine clearance \> 60 mL/min by the Cockcroft-Gault equation or equivalent
   2. Total bilirubin ≤ 1.5 × ULN (upper limit of normal)
   3. Serum albumin ≥ 2.5 g/dL.
   4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN or ≤ 5 × ULN in the presence of liver metastases
   5. International normalized ratio (INR) \< 1.3 or ≤ institutional ULN.
8. Life expectancy ≥ 12 weeks as estimated by the Investigator.
9. The patient must not have undergone any physical or pharmacological intervention with curative or palliative intent between the time of any of the diagnostic measures and the \[68Ga\]Ga-PTF PET/CT and \[18F\]FDG PET/CT scan.

Exclusion criteria:

Patients will be excluded if one or more of the following criteria are met:

1. Known hypersensitivity to any active pharmaceutical agent or constituent of the \[68Ga\]Ga-PTF and/or \[18F\]FDG investigational products.
2. Inability to lie still for the entire imaging time.
3. Any severe acute or active chronic infection, as judged by the Investigator, at the time of screening or within two months prior to screening that may interfere with the diagnostic properties of \[68Ga\]Ga-PTF PET/CT and/or \[18F\]FDG PET/CT imaging.
4. Patients with plasma glucose levels higher than 11 mmol/L or 200 mg/dL prior to \[18F\]FDG administration.
5. Administration of any anti-cancer therapy within 1 month prior to study entry.
6. Patients with complete resection of all tumor lesion(s).
7. Administration of another investigational medicinal product within 30 days or within 5 terminal elimination half-lives of previous investigational medicinal product, whichever is longer, prior to study entry.
8. Current greater than grade 2 toxicity from any reason, per US-NCI "Common Terminology Criteria for Adverse Events v5.0" (NCI CTCAE 2017) except if tumor-related.
9. Pregnant or breast-feeding women.
10. Concomitant prohibited treatment which may interfere with \[68Ga\]Ga-PTF PET/CT imaging (systemic corticosteroids) administered within the last 1 month prior to study start.
11. Colony-stimulating factor (CSF) therapy within 5 days prior to \[18F\]FDG PET/CT examination.
12. Any recent myocardial infarction, stroke, or osteomyelitis within two months prior screening.
13. \[18F\]FDG PET/CT imaging or \[68Ga\]Ga-PTF PET imaging performed prior to study entry.
14. Judged by the referring physician as not mentally or as not physically fit to understand and comply with protocol-related interventions and procedures (e.g., medically retarded, body weight \> 180 kg for PET scanner).
15. Body weight of less than 48 kg.
16. Any other concurrently active neoplasia, or other disease who could jeopardize study safety or data.

Primary outcomes:
measure: Sensitivity of [68Ga]Ga-PTF PET/CT imaging vs. [18F]FDG PET/CT imaging in tumor detection
timeFrame: Through study completion, an average of 6 months
measure: Specificity of [68Ga]Ga-PTF PET/CT imaging vs. [18F]FDG PET/CT imaging in tumor detection
timeFrame: Through study completion, an average of 6 months
Secondary outcomes:
measure: Proportion of patients with additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) compared to pre-PET conventional staging as assessed by questionnaires completed by the referring physicians
timeFrame: Through study completion, an average of 6 months
measure: Proportion of patients with a change in intended patient management due to additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) as assessed by questionnaires completed by the referring physicians
timeFrame: Through study completion, an average of 6 months
measure: Proportion of patients with additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) compared to pre-PET conventional staging as assessed by questionnaires completed by an Independent Committee
timeFrame: Through study completion, an average of 6 months
measure: Inter-observer agreement of local and central assessment in terms of staging
timeFrame: Through study completion, an average of 6 months
measure: Proportion of patients with nodal MZL with additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) compared to pre-PET conventional staging as assessed by questionnaires completed by the referring physicians
timeFrame: Through study completion, an average of 6 months
measure: Proportion of patients with extranodal MZL with additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) compared to pre-PET conventional staging as assessed by questionnaires completed by the referring physicians
timeFrame: Through study completion, an average of 6 months
measure: Proportion of patients with splenic MZL with additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) compared to pre-PET conventional staging as assessed by questionnaires completed by the referring physicians
timeFrame: Through study completion, an average of 6 months
measure: Proportion of patients with nodal MZL with a change in intended patient management due to additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) as assessed by questionnaires completed by the referring physicians
timeFrame: Through study completion, an average of 6 months
measure: Proportion of patients with extranodal MZL with a change in intended patient management due to additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF;[18F]FDG) as assessed by questionnaires completed by the referring physicians
timeFrame: Through study completion, an average of 6 months
measure: Proportion of patients with splenic MZL with a change in intended patient management due to additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) as assessed by questionnaires completed by the referring physicians
timeFrame: Through study completion, an average of 6 months
measure: Diagnostic performance, consisting of sensitivity and specificity, of each PET/CT imaging agent in tumor detection on a region-basis (eyes, ears, nose, throat, liver, spleen, gastrointestinal tract, bone marrow) confirmed by SoT or surrogate SoT
timeFrame: Through study completion, an average of 6 months
measure: Sensitivity of each PET/CT imaging agent in tumor detection on a patient-basis confirmed by SoT or surrogate SoT
timeFrame: Through study completion, an average of 6 months
measure: Positive and negative predictive values (PPV, NPV) of each PET/CT imaging agent to detect tumor on a patient-basis and lesion-basis
timeFrame: Through study completion, an average of 6 months
measure: Detection rate of each PET/CT imaging agent to detect tumor on a patient-basis and lesion-basis confirmed by SoT or surrogate SoT
timeFrame: Through study completion, an average of 6 months
measure: Proportion of patients with additional or less tumoral lesions detected by [68Ga]Ga-PTF PET/CT imaging compared to [18F]FDG PET/CT imaging
timeFrame: Through study completion, an average of 6 months
measure: Inter-reader and intra-reader agreement for tumor detection of each PET/CT imaging agent on a lesion-basis and patient-basis
timeFrame: Through study completion, an average of 6 months
measure: Reproducibility of [68Ga]Ga-PTF PET/CT imaging (reproducibility group)
timeFrame: Through study completion, an average of 6 months
measure: Maximum standardized uptake value (SUVmax), SUVpeak and SUV mean of each PET/CT imaging agent
timeFrame: Through study completion, an average of 6 months
measure: Target-to-background ratio (TBR) of each PET/CT imaging agent
timeFrame: Through study completion, an average of 6 months
measure: Contrast-to-noise ratio (CNR) of each PET/CT imaging agent
timeFrame: Through study completion, an average of 6 months
measure: Signal-to-noise ratio (CNR) of each PET/CT imaging agent
timeFrame: Through study completion, an average of 6 months
measure: Frequency and Severity of Adverse Events for each PET/CT imaging agent
timeFrame: Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent
measure: Frequency and kind of adverse effects present at the injection site
timeFrame: 2-3 hours after injection of each PET/CT imaging agent
measure: Clinical significance of abnormal results during physical examination
timeFrame: Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent
measure: Blood pressure (systolic and diastolic)
timeFrame: Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent
measure: Heart or pulse rate
timeFrame: Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent
measure: RR interval findings/abnormalities
timeFrame: Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent
measure: PQ interval findings/abnormalities
timeFrame: Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent
measure: QRS complex findings/abnormalities
timeFrame: Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent
measure: QT interval findings/abnormalities
timeFrame: Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent
measure: QTc interval findings/abnormalities
timeFrame: Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent
measure: Weight
timeFrame: Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent
Other outcomes:
measure: Sensitivity of [68Ga]Ga-PTF PET/CT imaging in detecting CXCR4 overexpressing tissue confirmed by a CXCR4 SoT (CXCR4 IHC)
timeFrame: Through study completion, an average of 6 months
measure: Specificity of [68Ga]Ga-PTF PET/CT imaging in detecting CXCR4 overexpressing tissue
timeFrame: Through study completion, an average of 6 months
measure: Receiver-operating-characteristic (ROC) curve analysis
timeFrame: Through study completion, an average of 6 months
measure: Determination of the area under the curve (AUC)
timeFrame: Through study completion, an average of 6 months
measure: Correlation of [68Ga]Ga-PTF uptake in PET and CXCR4 overexpression by IHC
timeFrame: Through study completion, an average of 6 months
measure: Correlation of the Ki-67 proliferation index with CXCR4 overexpression and with SUVmean on a lesion-basis
timeFrame: Through study completion, an average of 6 months
measure: Correlation of the Ki-67 proliferation index with CXCR4 overexpression and with SUVmax on a lesion-basis
timeFrame: Through study completion, an average of 6 months
measure: Rate of non-tumoral CXCR4-positive and CXCR4-negative lesions found in the [68Ga]Ga-PTF PET/CT imaging
timeFrame: Through study completion, an average of 6 months
measure: Percentage of patients with within-patient discordant lesions in terms of CXCR4 expression
timeFrame: Through study completion, an average of 6 months
measure: Positive predictive value (PPV) of [68Ga]Ga-PTF PET/CT imaging for detection of CXCR4 overexpressing tissue
timeFrame: Through study completion, an average of 6 months
measure: Negative predictive value (NPV) of [68Ga]Ga-PTF PET/CT imaging for detection of CXCR4 overexpressing tissue
timeFrame: Through study completion, an average of 6 months
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Marseille
country: France
facility: CHU La Timone
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Hôpital Cochin
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna
city: Meldola
country: Italy
facility: L'IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l
city: Milano
country: Italy
facility: Ospedale San Raffaele S.r.l.
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
Study officials:
affiliation: University Hospital Würzburg, Department of Nuclear Medicine
name: Andreas Buck, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: