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

Primary Purpose

Medullary Thyroid Carcinoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
111In-CP04
111In-CP04 with co-administration of gelofusine/gelaspan
Sponsored by
Paola Anna Erba
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Medullary Thyroid Carcinoma focused on measuring medullary thyroid carcinoma, MTC, new gastrin analog, 111In-CP04, CP04 indium, personalised diagnostics, personalised therapy, theranostics, advanced MTC, CCK-2/gastrin receptor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Nuclear Medicine, Innsbruck Medical University
  • Department of Nuclear Medicine, University Hospital Freiburg
  • Erasmus University Rotterdam
  • Department of Endocrinology, Jagiellonian University Medical College
  • Department of Nuclear Medicine, University Medical Centre Ljubljana

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

arm 1

arm 2

Arm Description

111In-CP04

111In-CP04 with co-administration of gelofusine/gelaspan

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CP04
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
Uptake of 111In-CP04 in tumor and other tissues
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
Pharmacokinetics of 111In-CP04
Area under the selected organs concentration versus time curve
Pharmacokinetics of 111In-CP04
Area under the blood concentration versus time curve

Secondary Outcome Measures

Diagnostic sensitivity/specificity of 111In-CP04 to detect cancer lesions
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
Comparison of pharmacokinetic/imaging effect of low and high peptide amount
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
Gelofusine/gelaspan injection and CP04 kidney uptake
To investigate the relative decrease of kidney dose after co-administration of nephroprotective agent - gelofusine/gelaspan
Dosimetry
Pharmacokinetics data for the assessment of organ and tissue radiation absorbed doses..

Full Information

First Posted
July 28, 2017
Last Updated
March 19, 2020
Sponsor
Paola Anna Erba
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
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1. Study Identification

Unique Protocol Identification Number
NCT03246659
Brief Title
Radiolabelled CCK-2/Gastrin Receptor Analogue for Personalized Theranostic Strategy in Advanced MTC
Acronym
GRAN-T-MTC
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
August 2016 (Actual)
Primary Completion Date
November 2018 (Actual)
Study Completion Date
November 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Paola Anna Erba
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Medullary Thyroid Carcinoma
Keywords
medullary thyroid carcinoma, MTC, new gastrin analog, 111In-CP04, CP04 indium, personalised diagnostics, personalised therapy, theranostics, advanced MTC, CCK-2/gastrin receptor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
Participant
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
arm 1
Arm Type
Experimental
Arm Description
111In-CP04
Arm Title
arm 2
Arm Type
Experimental
Arm Description
111In-CP04 with co-administration of gelofusine/gelaspan
Intervention Type
Drug
Intervention Name(s)
111In-CP04
Other Intervention Name(s)
111In-CP04 (DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2
Intervention Description
Radiopharmaceutical preparation
Intervention Type
Drug
Intervention Name(s)
111In-CP04 with co-administration of gelofusine/gelaspan
Other Intervention Name(s)
111In-CP04 (DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2
Intervention Description
Radiopharmaceutical preparation with co-administration of gelofusine/gelaspan
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CP04
Description
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
Time Frame
4 months
Title
Uptake of 111In-CP04 in tumor and other tissues
Description
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
Time Frame
72 hours from 111In-CP04 injection
Title
Pharmacokinetics of 111In-CP04
Description
Area under the selected organs concentration versus time curve
Time Frame
72 hours from 111In-CP04 injection
Title
Pharmacokinetics of 111In-CP04
Description
Area under the blood concentration versus time curve
Time Frame
72 hours from 111In-CP04 injection
Secondary Outcome Measure Information:
Title
Diagnostic sensitivity/specificity of 111In-CP04 to detect cancer lesions
Description
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
Time Frame
3 years
Title
Comparison of pharmacokinetic/imaging effect of low and high peptide amount
Description
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
Time Frame
3 years
Title
Gelofusine/gelaspan injection and CP04 kidney uptake
Description
To investigate the relative decrease of kidney dose after co-administration of nephroprotective agent - gelofusine/gelaspan
Time Frame
3 years
Title
Dosimetry
Description
Pharmacokinetics data for the assessment of organ and tissue radiation absorbed doses..
Time Frame
72 hours from 111In-CP04 injection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paola Anna Erba, Professor
Organizational Affiliation
Azienda Ospedaliero, Universitaria Pisana
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Nuclear Medicine, Innsbruck Medical University
City
Innsbruck
Country
Austria
Facility Name
Department of Nuclear Medicine, University Hospital Freiburg
City
Freiburg
Country
Germany
Facility Name
Erasmus University Rotterdam
City
Rotterdam
Country
Netherlands
Facility Name
Department of Endocrinology, Jagiellonian University Medical College
City
Kraków
Country
Poland
Facility Name
Department of Nuclear Medicine, University Medical Centre Ljubljana
City
Ljubljana
Country
Slovenia

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948680/
Description
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
URL
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817208/
Description
From preclinical development to clinical application: Kit formulation for radiolabelling the minigastrin analogue CP04 with In-111 for a first-in-human clinical trial

Learn more about this trial

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

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