To demonstrate a 25% increase of docetaxel in tumor tissue after intravenous with CriPec® docetaxel compared to Taxotere®. Additionally, systemic PK profile and adverse events will also be evaluated.
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To show a 25% difference in concentration of docetaxel in tumor tissue after
administration of CriPec® docetaxel compared to Taxotere®.
Secondary outcome
Systemic pharmacokinetics and adverse events:
1. Plasma levels of total and free docetaxel up to 24 hours after dosing and at
the time of biopsy; Cmax, Tmax, AUClast, AUCinf, Thalf, Cl, Vss in relation to
body weight (kg) where applicable.
3. The incidence of Grade 3 or 4 adverse events during cycle 1 and 2 according
to CTCAE, version 4.03.
Docetaxel PK and pathological changes in the skin after treatmet with CriPec®
docetaxel and Taxotere®.
Background summary
Many conventional chemotherapeutics including docetaxel (Taxotere®) have a
narrow therapeutic index with limitations of drug resistance and lack of
selectivity. Additionally, barriers at the tumor site such as abnormal blood
supply, abundant tumor stroma and high intratumoral pressure limit tumoral drug
penetration, leading to suboptimal therapeutic drug levels. CriPec® docetaxel
consists of docetaxel conjugated to a linker agent entrapped in a stabilized
CriPec® nanoparticle. CriPec® docetaxel has been designed to accumulate in
tumor tissue to a higher extent than native Taxotere® due to the *enhanced
permeability and retention* (EPR) effect. Subsequent release of docetaxel from
the entrapped particles will allow for an enhanced local anti-tumor effect,
whilst docetaxel exposure in non-tumor tissue will remain limited. Preclinical
data from mice provided that CriPec® docetaxel (30 mg/kg) had a 20-fold (P <
0.01) and 59-fold (P < 0.001) higher total docetaxel level as compared to
Taxotere® (30 mg/kg) two or 4 days after infusion, respectively. This is the
first attempt to provide proof of concept for this in a clinical setting.
Study objective
To demonstrate a 25% increase of docetaxel in tumor tissue after intravenous
with CriPec® docetaxel compared to Taxotere®. Additionally, systemic PK profile
and adverse events will also be evaluated.
Study design
This is a randomized cross-over study evaluating intratumoral PK of intravenous
CriPec® docetaxel compared to generic Taxotere®.
Intervention
Subjects will be randomized in a 1:1 ratio to receive CriPec® docetaxel in
cycle 1 and Taxotere® in cycle 2 (Arm A) or Taxotere® in cycle 1 and CriPec®
docetaxel in cycle 2 (Arm B). CriPec® docetaxel will be administered at a dose
of 75 mg/m2 (4-weekly, Q4W) and Taxotere® also at a dose of 75mg/m2 (3-weekly,
Q3W). Tumor biopsies will be taken at 6 different time points (resp. 24, 48,
72, 96, 168 (± 24 ) or 336 (± 24) hours) after infusion. For each time point 4
patients will be allocated. Additionally punch skin biopsies will obtained at
baseline and on day 8 of cycle 1 and 2 for PK analysis of docetaxel in the
skin. After completion of cycle 2, a radiographic evaluation will take place
and the patients will go off study. Subjects without evidence of disease
progression or drug related toxicity can continue treatment with Taxotere®
(75mg/m2, Q3W) according to local standard guidelines for Taxotere® treatment
until disease progression or unacceptable toxicity occurs.
Study burden and risks
Patients will be exposed to CriPec® docetaxel and Taxotere®. Taxotere® is a
registered chemotherapy. It is hypothesized that treatment with CriPec®
docetaxel will result in less side effects and a better antitumor activity. The
burden for patients participating in this study includes approximately 2x 24
hours hospital admissions, additional blood withdrawal for PK analyses (30 x
7ml), 8 outpatient clinic visits and two needle biopsy of the tumor and two
punch skin biopsies. The number of site visits during cycle 1 and cycle 2 is
more than the regular treatment with Taxotere®; participants have 6 additional
site visits. The main risks anticipated are: a small bleeding risk after the
biopsies, skin toxicity due to CriPec® docetaxel and other known side effects
related to Taxotere® for which the patients will carefully be monitored.
Groene Hilledijk 301
Rotterdam 3075 EA
NL
Groene Hilledijk 301
Rotterdam 3075 EA
NL
Listed location countries
Age
Inclusion criteria
Age * 18;Patients with advanced, unresectable and/or refractory solid tumors with no standard therapy options who could benefit from treatment with taxane containing chemotherapy;Signed informed consent;WHO Performance Status 0 or 1;Adequate organ function as defined by:;* Total bilirubine > 1.5 x ULN if no liver metastases (> 2 x ULN in patients with liver metastases). Except in case of documented Gilbert*s disease ;* AST or ALT > 2.5 x ULN if no liver metastases (> 5x ULN in patients with liver metastases);* Creatinine > 1.5 x ULN;Estimated life expectancy of at least 12 weeks;Willing to undergo repeated tumor and skin biopsies
Exclusion criteria
Pregnant or lactating patients;Less than 4 weeks (prior to Cycle 1 Day 1) treatment with another Investigational Product or participation in another investigational interventional study.;Less than 4 weeks since the last anti-cancer therapy prior to Cycle 1 Day 1;Toxicities incurred as a result of previous anti-cancer therapy that have not resolved to * grade 2 except skin toxicity, this should be grade 0 at the base line;Known hypersensitivity to any of the Investigational Product*s excipients or taxanes;Symptomatic brain metastasis ;Patients unable to undergo study procedures
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-001924-70-NL |
| CCMO | NL57671.056.16 |