Radiolabelled CCK-2/Gastrin Receptor Analogue for Personalized Theranostic Strategy in Advanced MTC

The study is a phase I multicentre randomized, open, parallel-arm clinical trial conducted to investigate the IMP, namely 111In-CP04.

The study consists of preclinical (to establish a clinically useful formulation for the radiolabelled peptide CP04), and a clinical step. The main objective of the clinical part of the project is to establish the safety of i.v. administration of a high peptide amount and to assess the tracer biodistribution and dosimetry in MTC and normal tissues and to determine critical organs as well as the evaluation of the potential of CCK2 receptor scintigraphy to detect cancer lesions for both low (10ug) and high (50ug) peptide amount and the decrease of kidney dose after co-administration of gelofusine /gelaspan as a nephroprotective agent. To achieve this, the following study design has been accepted: the first 4 patients will receive 2 peptide amount of CP04: low peptide amount (for diagnostic purpose) and high peptide amount (for therapeutic purpose) of CP04. If no SAE is present, the remaining pts will be randomized for 2 arms: high peptide amount of 111In-CP04 with and without gelofusine/gelaspan infusion.

It is expected that CCK-2/gastrin receptor imaging will become a valid diagnostic method for a specific non-invasive staging and follow-up of patients with MTC, and treatment of recurrent and disseminated disease will be more efficient with minimized nephro- and myelotoxicity (if 111In labelled).

The main goal of the study is to expand cancer preclinical research results on the usefulness of CCK-2/gastrin receptor in clinical practice. On the basis of last few years preclinical research outcome on new biomarkers, conjugate CP04 was chosen on the basis of its good stability and affinity to CCK-2/gastrin receptor in vitro, as well as its favourable biodistribution and pharmacodynamic properties in vivo, preclinically. Within this project the tracer 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 project may become the first step to establish a new, more effective strategy for the treatment of MTC patients leading to reduction of incidence and mortality as well as improvement of quality of life. CCK-2/gastrin receptors may become viable targets for radionuclide scintigraphy and radionuclide therapy, similarly to somatostatin receptors which have been instrumental to establish nuclear medicine efficacy in clinical practice. Achieving key project objectives (i.e. investigation of patients after administration of high peptide amount of the CCK-2/gastrin receptor labelled compound, performing complete patient peptide assessment and research nephrotoxicity in patients with or without administration for nephroprotective agent gelofusine/gelaspan), we will be able to define the exact molecular profile of an individual patient and tumour. Eventually, safe and efficacious personalized treatment will be planned using radiolabelled CCK-2/gastrin ligands of higher therapeutic efficacy.

Eligibility Criteria:
Inclusion Criteria:

Related to the medullary cancer of the thyroid:

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 OR
3. Doubling time (DT) of serum calcitonin level less than two years prior to study entry and negative imaging.
4. Karnofsky performance status \> 50%.
5. Life expectancy of more than 6 months.

   Related to the patient:
6. Male or female patients aged \>18 years without upper age limit.
7. Ability to understand and willingness to sign a written informed consent document.
8. Written informed consent obtained according to international guidelines and local laws.

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.

   Related to the patient:
6. Pregnancy, breast-feeding.
7. Known hypersensitivity to gastrin analogues.
8. Patients with concurrent illnesses that might preclude study completion or interfere with study results.
9. Patients with bladder outflow obstruction or unmanageable urinary incontinence.
10. Clinical diagnosis of disseminated intravascular coagulation.
11. Serum creatinine \>170 μmol/L, GFR \< 40 mL/min
12. Known history of hypersensitivity to gelofusine /gelaspan or any other contraindications to gelofusine/gelaspan infusion