A clinical phase I, open-label PET study with 89Zr CriPec docetaxel in patients with solid tumours to assess biodistribution and tumour accumulation of 89 Zr CriPec docetaxel

Completed

Conditions: cancer oncology
10027656

Registration Number: NL-OMON50409

Lead Sponsor: Vrije Universiteit Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 10

Inclusion Criteria

1. Age older or equal to 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
exists 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 long axis diameter of > 2 cm.
4. Performance status (WHO scale/ECOG) smaller or equal than 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 equal or> 1.5 x 109/L; platelets equal or > 100 x 109/L; Haemoglobin
equal or >* 6.0 mmol/L ( equal or >* 9.6 g/dL)
8. Creatinine ** 1.5 x upper limit of normal (ULN); or creatinine clearance
equal or > 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 ** 5 x ULN is allowed
10. Written informed consent according to local guidelines

Exclusion Criteria

* 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 grade 2 or higher skin toxicity as a result of prior treatment
with taxanes
* If excessive sequestering of 89Zr 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
* 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 28 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 mm Hg and/or diastolic > 100mm Hg)
* 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
* 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 York 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) or in male patients who are not surgically sterile
and who have female partners of childbearing potential
15. Evidence of any other medical conditions (such as psychiatric illness,
infectious diseases, drug or alcohol abuse, physical examination or laboratory
findings) that may interfere with the planned treatment, affect patient
compliance or place the patient at high risk from treatment-related
complications

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint of this study is detection (visual and quantitative) of<br /><br>89Zr CriPec® docetaxel in tumour lesions (the long axis diameter of a visually<br /><br>assessable and quantifiable lesion must be * 2 cm) .<br /><br><br /><br>The five largest lesions will be used for evaluation:<br /><br>- Visually: present/absent; present being as focally enhanced uptake on the PET<br /><br>scan with optimal contrast (2-96 h post injection).<br /><br>- Quantitatively: same tumour lesions measured in Standardized Uptake Value<br /><br>(SUV) using tumour volumes of interest (VOI). % Injected dose (ID)/ml above<br /><br>background and above blood will be determined.<br /><br><br /><br>To prevent undetectable uptake due to size the short axis diameter of at least<br /><br>one measurable lesions must be * 2 cm for each patient. Liver lesions may be<br /><br>excluded for analysis if excessive sequestering of 89Zr CriPec® docetaxel in<br /><br>healthy liver is observed.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary endpoints of the study are:<br /><br>* Dosimetry of 89Zr CriPec® docetaxel:<br /><br>o Organ dose (mSv) - recorded for each organ<br /><br>o Effective dose (mSv) * a single value for each subject<br /><br>* Define the optimal time point for PET imaging after 89Zr CriPec® docetaxel<br /><br>administration<br /><br>* Pharmacokinetics of 89Zr CriPec® docetaxel and total docetaxel<br /><br>* Biodistribution of low dose dose89Zr CriPec® docetaxel before and after<br /><br>administration of therapeutic dose of CriPec® docetaxel (quantified with %ID<br /><br>89Zr CriPec® docetaxel)<br /><br>* Adverse Effects using Common Terminology Criteria Adverse Events, version 4.0<br /><br>(CTCAE 4.0)<br /><br>* Correlation between side effects of CriPec® docetaxel and uptake of 89Zr<br /><br>CriPec® docetaxel in normal tissue<br /><br>* The correlation between tumour (quantification measures of) targeting of 89Zr<br /><br>CriPec® docetaxel and response to therapy.</p><br>