The identification of RCC is crucial for planning possible surgery and treatment. The aim of this study is to investigate the safety, tolerability, radiation dosimetry, as well as the diagnostic performance of 89Zr-girentuximab PET/CT in patients…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study will be to evaluate clinical safety and
tolerability of 89Zr-girentuximab.
Secondary outcome
- To determine the whole body radiation dosimetry of 89Zr-girentuximab in
patients with suspected CCRC
- To assess diagnostic image quality of 89Zr-girentuximab using a
time-of-flight PET (TOF-PET) compared a conventional PET (C-PET reconstruction)
- To assess diagnostic image quality of 89Zr-girentuximab using a 37 MBq (1
mCi) activity dose and different acquisition durations (5, 10, 15 vs. 20 min)
- To establish activity dose and recommended acquisition modalities for further
clinical development
Background summary
Distinct advantages of immunoPET as compared to immunoSPECT are the superior
resolution, the short acquisition time for whole-body 3D images, and the
potential for quantitative analysis of tumor targeting. Clinical immuno*PET
trials with 89Zr*labeled monoclonal antibodies (mAbs) have been performed or
are ongoing with at least 15 MAbs, including most of the FDA approved MAbs.
89Zr*immuno*PET has become an integrated part of the MAb development programs
of several of the world-leading pharmaceutical and biotech companies.
Girentuximab can be stably labeled with the PET radionuclide Zirconium- 89
(Zr-89; 89Zr) and in preclinical studies the in vivo distribution of
89Zr-girentuximab was shown to be identical to that of 111In-girentuximab. In
addition, due to prolonged trapping of the radiolabel in the tumor and
simultaneous washout from normal tissues, PET imaging with 89Zr-girentuximab
was shown to be superior to 124I-girentuximab. Combining the superior
characteristics of PET with the use of the residualizing 89Zr radionuclide are
major steps forward in the development of this imaging biomarker.
Study objective
The identification of RCC is crucial for planning possible surgery and
treatment. The aim of this study is to investigate the safety, tolerability,
radiation dosimetry, as well as the diagnostic performance of 89Zr-girentuximab
PET/CT in patients with suspected CCRC. The results of this study will be used
to pave the way for further studies with 89Zr-girentuximab as a PET/CT imaging
agent which was shown to have higher diagnostic resolution 124I-girentuximab in
animal studies due to prolonged trapping of the radiolabel in the tumor and
simultaneous washout from normal tissues. It is anticipated to develop
89Zr-girentuximab as an improved imaging agent for CCRC.
Study design
This will be an exploratory, open-label, Phase I study to evaluate safety,
tolerability, whole body dosimetry, and imaging properties of
89Zr-girentuximab, when image acquisition is made using different PET
reconstruction methods, namely time-of-flight (TOF-PET) and conventional (PET)
reconstruction, in order to estimate a possible impact of variable scanner
technology on image quality variability in a planned multi-centre study.
In addition, different acquisition durations (5 *20 min) will be explored using
an activity dose of 37 mBq (1 mCi), in order to establish, whether acquisition
time has an impact on diagnostic performance.
Study burden and risks
Given the well-known safety and tolerability of radiolabelled girentuximab and
the low doses used in this study, no harmful effects can be anticipated, and
the results of this study may contribute to the development of
89Zr-girentuximab as an improved imaging agent for CCRC. Although highly
unlikely, 89Zr-girentuximab may cause allergic-type reactions. The study
centres are well equipped to treat allergic/anaphylactic reactions.
Main Office, Suite 401, Flemington Road 55
North Melbourne VIC 3051
AU
Main Office, Suite 401, Flemington Road 55
North Melbourne VIC 3051
AU
Listed location countries
Age
Inclusion criteria
All patients must meet all of the following criteria:;- Written informed consent
- Male or female >50 years of age
- Clinical suspicion of CCRC, based on incidental imaging evidence of a renal mass, requiring further diagnostic work-up (incidentalomas), or patients with established diagnosis of CCRC requiring staging
- Life expectancy of at least 6 months
- Consent to practise contraception until end of study (7 days after 89Zr-girentuximab injection)
Exclusion criteria
A patient will be excluded from participation in the trial if one or more of the following criteria are met:;- Known hypersensitivity to girentuximab
- Known uncontrolled hyperthyreoidism
- Exposure to any experimental diagnostic or therapeutic drug within 30 days from the date of planned administration of 89Zr-girentuximab
- Exposure to any radiopharmaceutical within 30 days (corresponding to 8 half-lives of 89Zr) prior to the administration of 89Zr-girentuximab.
- Ongoing toxicity grade 2 from previous standard or investigational therapies (Common Terminology Criteria for Adverse Events [CTCAE] version 4.03)
- Planned (for the period between injection of 89Zr-girentuximab and imaging) antineoplastic therapies
- Established renal cell carcinomas of other histological entities than CCRC
- Known brain metastases
- Serious non-malignant disease (e.g. psychiatric, infectious, autoimmune or metabolic), that may interfere with the objectives of the study or with the safety or compliance of the subject, as judged by the investigator
- Pregnant or breast-feeding women. Female patients of childbearing potential or male patients with female partners of childbearing potential, unless willing to practice full and true sexual abstinence or being surgically/permanently sterile or with a history of hysterectomy for women, not willing to practice effective contraception by using: a non-oral, injected or implanted non-oestrogen progesterone based hormonal method, male condom, vaginal diaphragm, cervical cap, intrauterine device, during the study period and within a period of 28 days (corresponding to 8 half-lives of 89Zr) after receiving study drug.
11. Subjects not able to declare meaningful informed consent on their own (e.g. with legal guardian for mental disorders)
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 | EUCTR2017-004769-28-NL |
| CCMO | NL64206.091.17 |