Primary Objectives1. to establish the safety of intravenous administration of a therapeutic peptideamount of the CP042. to assess the biodistribution and dosimetry of 111In-CP04 in cancer and normal tissues and to determine critical organs.Secondary…
ID
Source
Brief title
Condition
- Endocrine neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Outcome measures
1. Safety of intravenous administration of CP04 at low-dose (diagnostic amount)
and high-dose (therapeutic amount) peptide radiolabelled with 200±10% MBq of
111In (diagnostic amount) will be assessed by type, frequency, severity, timing
and relation to the studied radiopharmaceutical administration of adverse
events and laboratory abnormalities based on Common Terminology Criteria for
Adverse Events (CTCAE) version 4.0
2. Biodistribution and pharmacokinetics\for target lesion and for discernible
organs will be evaluated from sequential planar images. Calculation of the
residence time of 111In in discernible thoracic and abdominal organs, target
lesion and blood will be performed and organ as well as tumour doses (mGy/MBq)
calculated. These data will provide all required data for evaluation of the
feasibility of a therapeutic application of CP04.
3. Diagnostic sensitivity/specificity of 111In CP04 to detect cancer lesions
for both diagnostic and therapeutic peptide amount by Qualitative Visual
Analysis (number of patients with uptake at site of lesion, the number of
lesions with abnormal tracer uptake at scintigraphy, the number and site of
lesions with pathological uptake detected per verifiable organ or body region
relative to those detected by conventional imaging)
4. Influence of a diagnostic amount of CP04 peptide vs. a therapeutic amount of
peptide on tumour and organ uptake, the identification of the time points
post-injection with the highest observed number of lesions and the highest
tumour/background ratios will be performed.
5. The relative decrease of kidney adsorbed dose after co-administration of
Gelofusine.
Secondary outcome
Not applicable
Background summary
Medullary thyroid carcinoma (MTC) is still one of the most challenging cancers
for both physicians and patients [1-4]. Epidemiological studies have shown that
during the past 30 years neither a change in stage at diagnosis nor improvement
in survival has occurred for MTC patients [5, 6].
Patients with metastatic MTC are left with few inefficient therapeutic options.
Therefore, it is necessary to develop alternative therapeutic strategies to
control tumour growth. The cholecystokinin 2 (CCK-2) receptor is overexpressed
in MTC with very high density and incidence of over 90%, as revealed by
autoradiographic studies. From the late 1990*s, a variety of CCK-2/gastrin
related peptides (members of the gastrin- and cholecystokinin families, or
possessing characteristics of both), were studied in vitro and in preclinical
animal models. In a comparison study performed within COST BM0607
(previous collaboration of the investigators under supervision of Prof. M. de
Jong, EMC, Rotterdam) the
DOTA-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (CP04)
showed the most promising characteristics in terms of high stability and
receptor affinity, high and persistent tumour uptake and low kidney retention
and was therefore selected for this clinical evaluation.
The aim of the project is to establish in a multinational cooperation in the
innovative field of targeted radionuclide therapy using the CCK-2/gastrin
receptor-seeking ligand CP04 radiolabelled with Indium-111 (111In) as imaging
biomarker.
Study objective
Primary Objectives
1. to establish the safety of intravenous administration of a therapeutic
peptideamount of the CP04
2. to assess the biodistribution and dosimetry of 111In-CP04 in cancer and
normal tissues and to determine critical organs.
Secondary Objectives
1. to evaluate the diagnostic potential of CCK2/gastrin receptor
ligand-scintigraphy to detect cancer lesions for both diagnostic and
therapeutic peptide amount
2. to evaluate the influence of a diagnostic amount of CP04 peptide on the
therapeutic amount of peptide vs. a therapeutic amount of peptide alone on
tumour and organ uptake
3. to investigate the relative decrease of kidney dose after co-administration
of nephroprotective agent * Gelofusine
Study design
The study is a phase I multicentre randomized, open, parallel-arm clinical
trial
Intervention
The research will undergo a scan with IN111-CP04 and possibly an administration
of Gelofusine if by lottery assigned
Study burden and risks
It is expected that within the outcomes of this project, the CCK-2/gastrin
receptors become viable targets for radionuclide scintigraphy and radionuclide
therapy, similarly to somatostatin receptors which were instrumental to
establish nuclear medicine efficacy in clinical practice. The novel vector may
get a chance to be introduced to clinical practice as a more selective and
efficient tool for the diagnosis, early detection and therapy of recurrent and
metastatic MTC. Furthermore, the results of this project may become the first
step to establish a new, more effective strategy for the treatment of MTC
patients, leading to reduction mortality as well as improvement of quality of
life of these patients.
Treatment options for MTC patients are very limited. According to data that
have been generated by different clinical research groups, treatment with
labelled CP04 may offer a safe and promising approach for MTC patients that
would until now receive sole best supportive care.
Side effects to be expected are limited and comparable with side effects of a
Pentagstrin® stimulation test or side effects seen after administration of
Demogastin 2, a recently investigated CCK-2R binding analogue. These are
self-limiting complaints like dizziness, flush, rise in heart rate, pressure on
the chest, nausea, and rarely some hypotension. These side effects disappeared
spontaneously, mostly within some minutes. Other potential risks are
haematomaof infection caused by intravenous drips or blood samples. Radiation
dose caused by administration of 111In-CP04 is within current levels of
standard diagnostic procedures. Depending on the medical situation of the
patients included in the study, they might have benefit for their own treatment.
Overall, the investigators believe that the benefits outweigh the risks for the
individual patient.
via Roma 55
Pisa 56123
IT
via Roma 55
Pisa 56123
IT
Listed location countries
Age
Inclusion criteria
1. Histologically documented medullary cancer of the thyroid.
2. Presence of more than one distant or nodal, surgically untreatable metastases confirmed with either 18F-FDG PET/CT or enhanced-CT or MRI.
3. Doubling time (DT) of serum calcitonin level within two years prior to study entry and no evidence of disease.
4. Karnofsky performance status >50%.
5. Life expectancy of more than 6 months.
6. Male or female patients aged >18 years without upper age limit.
Exclusion criteria
Related to the MTC:
1. Patients with surgically treatable medullary thyroid cancer.
2. Patients with history of second malignancy other than basal cell
carcinoma of the skin.
Related to previous or concomitant therapies :
3. Participation in any other investigational trial within 3 months of
study entry.
4. Previous external beam radiation therapy within two years.
5. Organ allograft requiring immunosuppressive therapy.
6. Treatment with Tyrosine kinase inhibitors
Related to the patient:
7. Pregnancy, breast-feeding.
8. Known hypersensitivity to gastrin analogues.
9. Patients with concurrent illnesses that might preclude study
completion or interfere with study results.
10. Patients with bladder outflow obstruction or unmanageable urinary
incontinence.
11. Clinical diagnosis of disseminated intravascular coagulation.
12. Serum creatinine >170 *mol/L, GFR < 40 mL/min
13. Known history of hypersensitivity to Gelofusine or any other contraindications to Gelofusine infusion
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 | EUCTR2015-000805-38-NL |
| CCMO | NL55280.078.16 |
| Other | UR.DBL.BLE.475.0324.2015 |