- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03246659
Radiolabelled CCK-2/Gastrin Receptor Analogue for Personalized Theranostic Strategy in Advanced MTC (GRAN-T-MTC)
Phase I Clinical Trial Using a Novel CCK-2/Gastrin Receptor-localizing Radiolabelled Peptide Probe for Personalized Diagnosis and Therapy of Patients With Progressive or Metastatic Medullary Thyroid Carcinoma
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).
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Innsbruck, Austria
- Department of Nuclear Medicine, Innsbruck Medical University
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Freiburg, Germany
- Department of Nuclear Medicine, University Hospital Freiburg
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Rotterdam, Netherlands
- Erasmus University Rotterdam
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Kraków, Poland
- Department of Endocrinology, Jagiellonian University Medical College
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Ljubljana, Slovenia
- Department of Nuclear Medicine, University Medical Centre Ljubljana
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Related to the medullary cancer of the thyroid:
- Histologically documented medullary cancer of the thyroid.
- Presence of more than one distant or nodal, surgically untreatable metastases confirmed with either 18F-FDG PET/CT or enhanced-CT or MRI OR
- Doubling time (DT) of serum calcitonin level less than two years prior to study entry and negative imaging.
- Karnofsky performance status > 50%.
Life expectancy of more than 6 months.
Related to the patient:
- Male or female patients aged >18 years without upper age limit.
- Ability to understand and willingness to sign a written informed consent document.
- Written informed consent obtained according to international guidelines and local laws.
Exclusion Criteria:
Related to the MTC:
- Patients with surgically treatable medullary thyroid cancer.
Patients with history of second malignancy other than basal cell carcinoma of the skin.
Related to previous or concomitant therapies :
- Participation in any other investigational trial within 3 months of study entry.
- Previous external beam radiation therapy within two years.
Organ allograft requiring immunosuppressive therapy.
Related to the patient:
- Pregnancy, breast-feeding.
- Known hypersensitivity to gastrin analogues.
- Patients with concurrent illnesses that might preclude study completion or interfere with study results.
- Patients with bladder outflow obstruction or unmanageable urinary incontinence.
- Clinical diagnosis of disseminated intravascular coagulation.
- Serum creatinine >170 μmol/L, GFR < 40 mL/min
- Known history of hypersensitivity to gelofusine /gelaspan or any other contraindications to gelofusine/gelaspan infusion
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: SEQUENTIAL
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: arm 1
111In-CP04
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Radiopharmaceutical preparation
Other Names:
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EXPERIMENTAL: arm 2
111In-CP04 with co-administration of gelofusine/gelaspan
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Radiopharmaceutical preparation with co-administration of gelofusine/gelaspan
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CP04
Time Frame: 4 months
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Safety of intravenous administration of CP04 at low peptide amount (for diagnostic purpose) and high peptide amount (for therapeutic purpose) radiolabelled with 200±10% MBq of 111In will be assessed by type, frequency, severity, timing and relation to the studied radiopharmaceutical Safety of intravenous administration of CP04 at low peptide amount (for diagnostic purpose) and high peptide amount (for therapeutic purpose) radiolabelled with 200±10% MBq of 111In 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
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4 months
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Uptake of 111In-CP04 in tumor and other tissues
Time Frame: 72 hours from 111In-CP04 injection
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The radioactivity uptake of 111In-CP04 will be assessed in the tumor lesions and in other tissues naturally expressing CCK2 receptors, based on the planar and SPECT/CT images (expressed as the ratio of counts over the region of interest (ROI) selected over the target tissue compared to the counts over the equivalent region in patient's body which is not taking up the 111In-CP04), otherwise described as target to non target ratio T/N
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72 hours from 111In-CP04 injection
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Pharmacokinetics of 111In-CP04
Time Frame: 72 hours from 111In-CP04 injection
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Area under the selected organs concentration versus time curve
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72 hours from 111In-CP04 injection
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Pharmacokinetics of 111In-CP04
Time Frame: 72 hours from 111In-CP04 injection
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Area under the blood concentration versus time curve
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72 hours from 111In-CP04 injection
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Diagnostic sensitivity/specificity of 111In-CP04 to detect cancer lesions
Time Frame: 3 years
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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
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3 years
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Comparison of pharmacokinetic/imaging effect of low and high peptide amount
Time Frame: 3 years
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To evaluate the influence of a low amount of CP04 peptide on the high amount of peptide vs. the high amount of peptide alone on tumour and organ uptake
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3 years
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Gelofusine/gelaspan injection and CP04 kidney uptake
Time Frame: 3 years
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To investigate the relative decrease of kidney dose after co-administration of nephroprotective agent - gelofusine/gelaspan
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3 years
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Dosimetry
Time Frame: 72 hours from 111In-CP04 injection
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Pharmacokinetics data for the assessment of organ and tissue radiation absorbed doses..
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72 hours from 111In-CP04 injection
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Paola Anna Erba, Professor, Azienda Ospedaliero, Universitaria Pisana
Publications and helpful links
Helpful Links
- Preclinical pharmacokinetics, biodistribution, radiation dosimetry and toxicity studies required for regulatory approval of a phase I clinical trial with 111In-CP04 in medullary thyroid carcinoma patients
- From preclinical development to clinical application: Kit formulation for radiolabelling the minigastrin analogue CP04 with In-111 for a first-in-human clinical trial
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Endocrine Gland Neoplasms
- Head and Neck Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Carcinoma
- Thyroid Diseases
- Thyroid Neoplasms
- Carcinoma, Neuroendocrine
- Physiological Effects of Drugs
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Plasma Substitutes
- Blood Substitutes
- Polygeline
- Gastrins
Other Study ID Numbers
- GRAN-T-MTC
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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