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Radiolabelled CCK-2/Gastrin Receptor Analogue for Personalized Theranostic Strategy in Advanced MTC (GRAN-T-MTC)

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ClinicalTrials.gov Identifier: NCT03246659
Recruitment Status : Recruiting
First Posted : August 11, 2017
Last Update Posted : August 16, 2017
Sponsor:
Collaborators:
Jagiellonian University
University Hospital Freiburg
Medical University Innsbruck
University Medical Centre Ljubljana
NATIONAL CENTRE FOR NUCLEAR RESEARCH, Poland
Erasmus Medical Center
INRASTES, NCSR Demokritos, Athens, Greece
Information provided by (Responsible Party):
Paola Anna Erba, Azienda Ospedaliero, Universitaria Pisana

Brief Summary:

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).


Condition or disease Intervention/treatment Phase
Medullary Thyroid Carcinoma Drug: 111In-CP04 Drug: 111In-CP04 with co-administration of gelofusine/gelaspan Phase 1

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 2016
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : November 2018


Arm Intervention/treatment
Experimental: arm 1
111In-CP04
Drug: 111In-CP04
Radiopharmaceutical preparation
Other Name: 111In-CP04 (DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2

Experimental: arm 2
111In-CP04 with co-administration of gelofusine/gelaspan
Drug: 111In-CP04 with co-administration of gelofusine/gelaspan
Radiopharmaceutical preparation with co-administration of gelofusine/gelaspan
Other Name: 111In-CP04 (DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CP04 [ Time Frame: 4 months ]
    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

  2. Uptake of 111In-CP04 in tumor and other tissues [ Time Frame: 72 hours from 111In-CP04 injection ]
    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

  3. Pharmacokinetics of 111In-CP04 [ Time Frame: 72 hours from 111In-CP04 injection ]
    Area under the selected organs concentration versus time curve

  4. Pharmacokinetics of 111In-CP04 [ Time Frame: 72 hours from 111In-CP04 injection ]
    Area under the blood concentration versus time curve


Secondary Outcome Measures :
  1. Diagnostic sensitivity/specificity of 111In-CP04 to detect cancer lesions [ Time Frame: 3 years ]
    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

  2. Comparison of pharmacokinetic/imaging effect of low and high peptide amount [ Time Frame: 3 years ]
    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

  3. Gelofusine/gelaspan injection and CP04 kidney uptake [ Time Frame: 3 years ]
    To investigate the relative decrease of kidney dose after co-administration of nephroprotective agent - gelofusine/gelaspan

  4. Dosimetry [ Time Frame: 72 hours from 111In-CP04 injection ]
    Pharmacokinetics data for the assessment of organ and tissue radiation absorbed doses..



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03246659


Contacts
Contact: Alicja Hubalewska-Dydejczyk, Professor 0048 12 424 75 20 alicja.hubalewska-dydejczyk@uj.edu.pl
Contact: Paola Anna Erba, Professor 00 39 050 992 115 paola.erba@unipi.it

Locations
Austria
Department of Nuclear Medicine, Innsbruck Medical University Recruiting
Innsbruck, Austria
Contact: Irene Virgolini, Professor    0043 125 048 0951    irene.virgolini@uki.at   
Contact: Clemens Decristoforo, Professor    0043 125 048 0951    Clemens.Decristoforo@tirol-kliniken.at   
Principal Investigator: Irene Virgolini, Professor         
Germany
Department of Nuclear Medicine, University Hospital Freiburg Not yet recruiting
Freiburg, Germany
Contact: Helmut Mäcke, Professor    0049 761 270 74220    Helmut.maecke@uniklinik-freiburg.de   
Principal Investigator: Helmut Mäcke, Professor         
Netherlands
Erasmus University Rotterdam Not yet recruiting
Rotterdam, Netherlands
Contact: Marion Hendriks-de Jong, Professor    0031107035781    m.hendriks-dejong@erasmusmc.nl   
Contact: Mark Konijnenberg, PhD    0031107035781    m.konijnenberg@erasmusmc.nl   
Principal Investigator: Marion Hendriks-de Jong, Professor         
Poland
Department of Endocrinology, Jagiellonian University Medical College Active, not recruiting
Kraków, Poland
Slovenia
Department of Nuclear Medicine, University Medical Centre Ljubljana Recruiting
Ljubljana, Slovenia
Contact: Katja Zalatel, doc.dr.    0038 615 223 553    katja.zaletel@kclj.si   
Contact: Petra Kolenc Peitl, PhD       petra.peitl@kclj.si   
Principal Investigator: Katja Zalatel, doc.dr.         
Sponsors and Collaborators
Paola Anna Erba
Jagiellonian University
University Hospital Freiburg
Medical University Innsbruck
University Medical Centre Ljubljana
NATIONAL CENTRE FOR NUCLEAR RESEARCH, Poland
Erasmus Medical Center
INRASTES, NCSR Demokritos, Athens, Greece
Investigators
Principal Investigator: Paola Anna Erba, Professor Azienda Ospedaliero, Universitaria Pisana

Additional Information:
Responsible Party: Paola Anna Erba, Professor, Azienda Ospedaliero, Universitaria Pisana
ClinicalTrials.gov Identifier: NCT03246659     History of Changes
Other Study ID Numbers: GRAN-T-MTC
First Posted: August 11, 2017    Key Record Dates
Last Update Posted: August 16, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Paola Anna Erba, Azienda Ospedaliero, Universitaria Pisana:
medullary thyroid carcinoma
MTC
new gastrin analog
111In-CP04
CP04 indium
personalised diagnostics
personalised therapy
theranostics
advanced MTC
CCK-2/gastrin receptor

Additional relevant MeSH terms:
Carcinoma
Thyroid Diseases
Thyroid Neoplasms
Carcinoma, Neuroendocrine
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Nerve Tissue
Radiopharmaceuticals
Gastrins
Polygeline
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Plasma Substitutes
Blood Substitutes