PET Study With [89Zr]-Df-CriPec® Docetaxel

Study Overview
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Brief Summary
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A clinical phase I, open-label PET study with [89Zr]-Df-CriPec® docetaxel in patients with solid tumours to assess biodistribution and tumour accumulation of [89Zr]-Df-CriPec® docetaxel.

Detailed Description
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After patient inclusion an fludeoxyglucose-18 ([18F]-FDG) PET scan will be performed to delineate viable tumour lesions. On day 1, patients will receive a low dose of [89Zr]-Df-CriPec® docetaxel (corresponding to approximately 0.1-1 mg docetaxel) followed by maximally 3 [89Zr] PET scans (timing of PET scan can be adapted depending on results obtained, within timeframe of 2 h - 9 days after administration) to evaluate biodistribution and tumour uptake. Two weeks later, the patients will receive unlabelled CriPec® docetaxel up to the Recommended Phase II Dose (RP2D) given every 3 weeks (Q3W) that will be determined in the phase I NAPOLY trial (CT-CL01), immediately followed by a second low dose of [89Zr]-Df-CriPec® docetaxel and maximally 3 [89Zr]PET scans (timing of PET scan can be adapted depending on results obtained, within timeframe of 2 hrs - 9 days after administration) to evaluate biodistribution and tumour uptake with therapeutic dosage.

Official Title
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A Clinical Phase I, Open-label, PET Study With [89Zr]-Df-CriPec® Docetaxel in Patients With Solid Tumours to Assess Biodistribution and Tumour Accumulation of [89Zr]-Df-CriPec® Docetaxel

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: Cripec Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria To be eligible to participate in this study, candidates must meet the following eligibility criteria: 1. Age ≥ 18 years 2 A pathologically confirmed diagnosis of advanced, recurrent and progressive cancer that is refractory to standard therapy or for which no standard therapy exist and where treatment with a taxane is an appropriate treatment option 3. Measurable or evaluable disease according to RECIST criteria v.1.1 Patient must have at least one measurable lesion with a short axis diameter of ≥ 2 cm. 4. Performance status (WHO scale/ ECOG) ≤ 1 (appendix 2) 5. Estimated life expectancy of at least 12 weeks 6. Toxicities incurred as a result of previous anti-cancer therapy (radiation therapy, chemotherapy, or surgery) must be resolved to ≤ grade 2 (as defined by CTCAE version 4.0) 7. ANC ≥ 1.5 x10E9/L; platelets ≥ 100 x 10E9/L; Haemoglobin ≥ 6.0 mmol/L (≥ 9.6 g/dL) 8. Creatinine ≤ 1.5 x upper limit of normal (ULN); or creatinine clearance ≥ 60 mL/ min (Cockcroft-Gault) 9 Serum bilirubin ≤1.5 x ULN, alkaline phosphatase, ASAT and ALAT ≤ 2.5 x ULN, unless related to liver metastases, in which case ≤ 5x ULN is allowed 10 Written informed consent according to local guidelines Exclusion Criteria Candidates will be excluded from study entry if any of the following exclusion criteria are met: Less than 4 weeks since the last treatment with other anti-cancer therapies, (i.e. endocrine therapy, immunotherapy, radiotherapy, chemotherapy, etc.), less than 8 weeks for cranial radiotherapy, and less than 6 weeks for nitrosoureas and mitomycin C prior to first study treatment. A history of skin toxicity as a result of prior treatment with taxanes If excessive sequestering of [ 89 Zr] CriPec®docetaxel in healthy liver is observed in the first 3 patients, patients with only liver lesion will not be eligible. Current or recent (within 28 days of first study treatment) treatment with another investigational drug or participation in another investigational study. Active or symptomatic brain metastases. Patients must be on a stable or deceasing dose of corticosteroids and/ or have no requirement for anticonvulsants for 5 days prior to Cycle 1 Day 1. Current malignancies at other sites, with exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin Major surgical procedure (including open biopsy, excluding central line IV and port-a- cath) within 27 days prior to the first study treatment, or anticipation of the need for major surgery during the course of the study treatment Uncontrolled hypertension (systolic >150 mmHg and/ or diastolic > 100 mmHg) Grade ≥ 2 motor or sensory neuropathy symptoms (as defined by CTCAE version 4.03) Known hypersensitivity to any of the study drugs or excipients or taxanes Any active skin condition associated with impaired skin integrity exposing the patient at risk to develop skin toxicity 12 Clinically significant (i.e. active) cardiovascular disease defined as: Stroke within ≤ 6 months prior to first study treatment; Transient Ischemic Attack (TIA) within ≤ 6 months prior to first study treatment ; Myocardial infarction within ≤ 6 months prior to first study treatment; Unstable angina; New Yotk Heart Association (NYHA) Grade II or greater Congestive Heart Failure (CHF); Serious cardiac arrhythmia requiring medication; Clinically relevant pathologic findings in electrocardiogram (ECG) Left ventricle Ejection Fraction (LVEF) by MUGA or ECHO < 50% 13 Patients who are pregnant or breastfeeding 14 Absence of effective means of contraception as of Run-in Day 1 in female patients of childbearing potential (defined as < 2 years after last menstruation and not surgically sterile) ore in male patients who are not surgically sterile and who have female partners if childbearing potential 15 Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, drug or alcohol abuse, physical examination or laboratory finding) that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment- related complications

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Phase I, open-label, single centre immune-PET study with [89Zr]-Df-CriPec® docetaxel in patients with solid tumours to assess biodistribution and tumour accumulation of [89Zr]-Df-CriPec® docetaxel
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients [89Zr]-Df-CriPec® docetaxel<br>Day 1 of the Run-in a low dose of [89Zr -Df-CriPec® docetaxel (corresponding to 0.1- 2 mg docetaxel). On Cycle 1 Day 1, the patients will receive unlabelled CriPec® docetaxel of a variable dose up to 60mg/m2 followed < 2 h by a second low dose of [89Zr]-Df-CriPec® docetaxel. On day 1 of each subsequent cycle, patients will only receive unlabelled CriPec® docetaxel . The dose will be the same as was given on Cycle 1 Day 1. For the following patients the dose of unlabelled CriPec® docetaxel combined with the low dose of [89Zr]-Df- CriPec® docetaxel will be variable but never exceed the highest dose of unlabelled CriPec® docetaxel that was determined to be safe in the phase I NAPOLY trial (CT-CL01). | Drug: Cripec Docetaxel<br>* 89 Zirconium Cripec Docetaxel PET<br>* Other names: 89 Zirconium Cripec Docetaxel PET;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection (visual) of [89Zr]-Df-CriPec® docetaxel in tumour lesions (the short axis diameter of a visually assessable and quantifiable lesion must be ≥ 2 cm) | Visual detection (absent/present) of tumor uptake | 14 days | 
| Detection (quantitative) of [89Zr]-Df-CriPec® docetaxel in tumour lesions (the short axis diameter of a visually assessable and quantifiable lesion must be ≥ 2 cm) | Measured by SUVpeak values of visual positive lesions | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dosimetry of [89Zr]-Df-CriPec® docetaxel | Based on 89Zr PK activity concentration (Bq/ml) and biodistribution [89Zr]-Df-CriPec® docetaxel scans | 14 days | 
| Optimal time point for PET imaging after [89Zr]-Df-CriPec® docetaxel administration | As assesed by a multidisciplinairy team | 14 days | 
| Linearity between [89Zr]-Df-CriPec® docetaxel and total docetaxel | Assessment of 89Zr PK (Bq/ml) and total docetaxel (ng/ml) | 14 days | 
| Biodistribution of low dose dose [89Zr]-Df-CriPec® docetaxel before and after administration of therapeutic dose of CriPec® docetaxel (quantified with %ID [89Zr] CriPec® docetaxel) | Measured by defining volumes of interest (VOI) of various organs on PET scan and calculating %ID/kg | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nanoparticles, Positron-Emission Tomography, Docetaxel, Neoplasms, Quantification