Intratumoural Injection of a Novel NanoZolid®-Docetaxel Depot Formulation in Patients With Advanced Solid Tumours

A Phase Ia/Ib, First-in-human, Open Label, Multicentre, Dose-escalation and Dose-expansion Study of a Novel NanoZolid®-Docetaxel Depot Formulation (NZ-DTX Depot) Given as an Intra-tumoural Injection in Patients With Advanced Solid Tumours

This is a multicentre, open-label, first in man, study of a novel NanoZolid®-docetaxel depot formulation (NZ-DTX Depot) given as an intra-tumoural injection in patients with advanced solid tumours. The study includes a dose escalation part and a dose expansion part.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: Docetaxel

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Herlev Hospital
• Lithuania
  • Kaunas, Lithuania
    • Lithuanian University of Health Sciences
  • Vilnius, Lithuania
    • National Cancer Institute
• Sweden
  • Stockholm, Sweden
    • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Signed written informed consent granted before undertaking any study-specific procedures;
2. Male or female patient ≥18 years of age on the day of consenting to the study;
3. Histologically or cytologically confirmed diagnosis of solid cancer;

4. At least 1 advanced solid, palpable, cutaneous or subcutaneous tumour lesion with following characteristics:

   • a cutaneous lesion with of thickness ≥4 mm and diameter ≥25 mm at the longest axis, or
   • a subcutaneous lesion of diameter ≥20 mm at the longest and the shortest axis;
5. Eastern Co-operative Oncology Group (ECOG) performance status (PS) 0-2;

6. Patient from one the following categories:

   • Patient for whom no standard therapy exists, or standard therapy is contraindicated, or
   • Patient who is scheduled for other anti-cancer treatment (e.g. radiotherapy, immunological treatment, surgery) which will start after completion of at least one treatment cycle of NZ-DTX, i.e after the end-of-study (EOS) visit.

Exclusion Criteria:

1. Known hypersensitivity to any of the excipients in the NZ-DTX Depot formulation (docetaxel, calcium sulphate, sodium carboxymethylcellulose);
2. Life expectancy <3 months;
3. Bleeding deficiencies or ongoing anticoagulant therapy that would put the patient at increased risk of clinically significant bleeding, in the judgement of the Investigator. If the patient has an international normalised ratio (INR) below 1.2 the Investigator may judge if interruption of anticoagulant therapy is warranted;

4. Any of the following abnormal laboratory values at screening;

   • Bone marrow function:

     • Absolute neutrophil count (ANC) <1.5 x 109/l;
     • Platelet count <100 x 109/l;
     • Haemoglobin <9.0 mg/dl.

   • Coagulation:

     - International Normalized Ratio (INR) >1.2.

   • Hepatic, renal, and biochemistry parameters:

     • Aspartate transaminase (AST) or alanine transaminase (ALT) >2.5 x upper limit of normal (ULN) (>5 x ULN if liver metastases present)*;
     • Alkaline phosphatase (ALP) >2.5 x ULN;
     • Total bilirubin >1.5 x ULN;

     • Estimated glomerular filtration rate (eGFR) <40 ml/min/1.73 m² using the Modified Cockcroft & Gault formula.

       • For patients with liver impairment who have serum transaminase levels (ALT and/or AST) greater than 1.5 times x ULN - the doses will be restricted to max. 75mg/m2. In the event this is not possible the patient will not be included.
5. Severe fluid retention, e.g. pulmonary oedema, pleural effusion, pericardial effusion or ascites;
6. Clinically significant heart disease (i.e. heart failure or myocardial infarction within 6 months of screening, instable angina pectoris);
7. History of thromboembolic or cerebrovascular events within 6 months of screening;
8. Major surgery within 2 weeks of screening, or patient not recovered from major surgery;
9. Known untreated or uncontrolled acute infection, including urinary tract infection, within 7 days of screening;
10. Not recovered from Grade 2 or higher adverse events (AEs) due to previous treatments, excepting alopecia;
11. Concurrent participation in another investigational study;
12. Last investigational drug administration in a prior investigational study within 14 days of study treatment initiation or <5 times the half-life of the investigational drug, whichever is longer;
13. Last administration of other anti-neoplastic drug within 14 days of study treatment initiation;
14. Radiotherapy of lesion to be injected within 4 weeks of first treatment with NZ-DTX Depot, or irradiated lesion to be injected without signs of disease progression since irradiation;
15. For men and women of childbearing potential: Unwillingness to follow contraception requirements;
16. Female patients with planned or current pregnancy and/or currently breastfeeding;
17. Any other severe, acute or chronical medical or psychiatric condition or laboratory abnormality that, in the judgement of the Investigator, would make the patient inappropriate for study participation.

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: NZ-DTX Depot	Drug: Docetaxel; Docetaxel in NanoZolid formulation, for intratumoural injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) of NZ-DTX Depot given as an intra-tumoural injection in solid, palpable, cutaneous or subcutaneous tumour lesions.	The MTD will be determined by incidence of DLTs	5 weeks
The recommended Phase 2 dose (RP2D) of NZ-DTX Depot given as an intra-tumoural injection in a solid, palpable cutaneous or subcutaneous tumour lesion.	The RP2D will be determined by frequency and severity of adverse events	5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and severity of treatment-emergent adverse events [safety and tolerability] following an intratumoural injection of NZ-DTX Depot	Frequency and severity of treatment-emergent adverse events	5 weeks
Plasma concentration of docetaxel, following an intratumoural injection of NZ-DTX Depot	Plasma concentration of docetaxel	5 weeks
Anti-tumour effect following an intratumoural injection of NZ-DTX Depot	Tumour response by RECIST	5 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of immune biomarkers in plasma, following an intratumoural injection of NZ-DTX Depot	Analysis of cytokines in plasma	9 weeks
Presence of immune biomarkers in tissue, following an intratumoural injection of NZ-DTX Depot	Immunohistochemistry analysis [PD-L1] in tissue	9 weeks

Collaborators and Investigators

• Sponsor: Lidds AB
• Investigators: Study Director: Charlotta Gauffin, PhD, Lidds AB

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2019
• Primary Completion (Actual): October 7, 2021
• Study Completion (Actual): October 7, 2021

Study Registration Dates

• First Submitted: March 18, 2021
• First Submitted That Met QC Criteria: March 19, 2021
• First Posted (Actual): March 22, 2021

Study Record Updates

• Last Update Posted (Actual): December 30, 2021
• Last Update Submitted That Met QC Criteria: December 22, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: NZ-DTX-001

Drug and device information, study documents

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