Medullary Thyroid CarcinomaPhase 1GRAN-T-MTCNCT03246659
Radiolabelled CCK-2/Gastrin Receptor Analogue for Personalized Theranostic Strategy in Advanced MTC
A Phase 1 study testing 111In-CP04 and 111In-CP04 with co-administration of gelofusine/gelaspan in people with Medullary Thyroid Carcinoma, run by Paola Anna Erba at 5 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Medullary Thyroid Carcinoma
- What is being tested?
- 111In-CP04 and 111In-CP04 with co-administration of gelofusine/gelaspan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 5 sitesin 5 countries
- Study dates
- Aug 2016to Nov 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
Austria1 site
Department of Nuclear Medicine, Innsbruck Medical University
Innsbruck
Germany1 site
Department of Nuclear Medicine, University Hospital Freiburg
Freiburg im Breisgau
Poland1 site
Department of Endocrinology, Jagiellonian University Medical College
Krakow
Slovenia1 site
Department of Nuclear Medicine, University Medical Centre Ljubljana
Ljubljana
About this study
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
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).
Read the 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.
- Conditions
- Medullary Thyroid Carcinoma
- Being tested
- 111In-CP04, 111In-CP04 with co-administration of gelofusine/gelaspan
- Keywords
- medullary thyroid carcinoma, MTC, new gastrin analog, 111In-CP04, CP04 indium, personalised diagnostics, personalised therapy, theranostics, advanced MTC, CCK-2/gastrin receptor
- Medical subject headings
- Carcinoma, Medullary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
111In-CP04Drug
Also called 111In-CP04 (DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2
Radiopharmaceutical preparation
111In-CP04 with co-administration of gelofusine/gelaspanDrug
Also called 111In-CP04 (DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2
Radiopharmaceutical preparation with co-administration of gelofusine/gelaspan
| Study group | Role | What they receive |
|---|---|---|
| arm 1 | Experimental | 111In-CP04 Receives: Drug: 111In-CP04 |
| arm 2 | Experimental | 111In-CP04 with co-administration of gelofusine/gelaspan Receives: Drug: 111In-CP04 with co-administration of gelofusine/gelaspan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 4 months
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
Measured: 72 hours from 111In-CP04 injection
Pharmacokinetics of 111In-CP04
Area under the selected organs concentration versus time curve
Measured: 72 hours from 111In-CP04 injection
Pharmacokinetics of 111In-CP04
Area under the blood concentration versus time curve
Measured: 72 hours from 111In-CP04 injection
Secondary outcomes (4)
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
Measured: 3 years
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
Measured: 3 years
Gelofusine/gelaspan injection and CP04 kidney uptake
To investigate the relative decrease of kidney dose after co-administration of nephroprotective agent - gelofusine/gelaspan
Measured: 3 years
Dosimetry
Pharmacokinetics data for the assessment of organ and tissue radiation absorbed doses..
Measured: 72 hours from 111In-CP04 injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2017
- Study startAug 2016
- Primary completionNov 2018
- Study completionNov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Medullary Thyroid CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Paola Anna Erba
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Sponsor-investigator, Paola Anna Erba, Azienda Ospedaliero, Universitaria Pisana
- Investigators
- Paola Anna Erba, Professor, Principal investigator, Azienda Ospedaliero, Universitaria Pisana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03246659
- Sponsor's protocol ID
- GRAN-T-MTC
- Acronym
- GRAN-T-MTC
- Status last verified
- Mar 2020
- First submitted
- 28 Jul 2017
- Last updated
- 20 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03246659
- Acronym / sponsor ID
- GRAN-T-MTC / GRAN-T-MTC
- Conditions
- Medullary Thyroid Carcinoma
- Keywords
- medullary thyroid carcinoma, MTC, new gastrin analog, 111In-CP04, CP04 indium, personalised diagnostics, personalised therapy, theranostics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Paola Anna ErbaUniversity, hospital or other
- 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
- Study start
- Aug 2016 (actual)
- Primary completion
- Nov 2018 (actual)
- Study completion
- Nov 2018 (actual)
- First posted
- 11 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| arm 1 | Experimental | Drug: 111In-CP04111In-CP04 |
| arm 2 | Experimental | Drug: 111In-CP04 with co-administration of gelofusine/gelaspan111In-CP04 with co-administration of gelofusine/gelaspan |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (15 listed)
- Patients with surgically treatable medullary thyroid cancer.
- Patients with history of second malignancy other than basal cell carcinoma of the skin.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 111In-CP04Also: 111In-CP04 (DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2Radiopharmaceutical preparation | Drug | arm 1 |
| 111In-CP04 with co-administration of gelofusine/gelaspanAlso: 111In-CP04 (DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2Radiopharmaceutical preparation with co-administration of gelofusine/gelaspan | Drug | arm 2 |
Primary outcome
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
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
Pharmacokinetics of 111In-CP04
Time frame: 72 hours from 111In-CP04 injection
Area under the selected organs concentration versus time curve
Pharmacokinetics of 111In-CP04
Time frame: 72 hours from 111In-CP04 injection
Area under the blood concentration versus time curve
4 secondary outcomes
Diagnostic sensitivity/specificity of 111In-CP04 to detect cancer lesions
Time frame: 3 years
Comparison of pharmacokinetic/imaging effect of low and high peptide amount
Time frame: 3 years
Gelofusine/gelaspan injection and CP04 kidney uptake
Time frame: 3 years
Dosimetry
Time frame: 72 hours from 111In-CP04 injection
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2020.
- 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 patientsLink provided by the sponsor.
- From preclinical development to clinical application: Kit formulation for radiolabelling the minigastrin analogue CP04 with In-111 for a first-in-human clinical trialLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Medullary Thyroid Carcinoma
RecruitingObservational study
Clinical and Genetic Studies in Familial Non-medullary Thyroid Cancer
Non-Medullary Thyroid Cancer
Active, not recruitingObservational study
Natural History Study of Children and Adults With Medullary Thyroid Cancer
Medullary Thyroid Cancer
RecruitingObservational study
68Ga-labeled Cholecystokinin Receptor (CCK2R) Targeted Molecular Probes in Early Tumor Diagnosis
Medullary Thyroid Carcinoma, Small Cell Lung Cancer ( SCLC )
RecruitingPhase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma
Active, not recruitingPhase 2
Phase II Trial of Ubamatamab Alone or in Combination With Cemiplimab in MUC16-Expressing SMARCB1-Deficient Malignancies
SMARCB1-Deficient Malignancies, Epithelioid Sarcoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paola Anna Erba, Professor principal investigator
Azienda Ospedaliero, Universitaria Pisana
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 111In-CP04 and 111In-CP04 with co-administration of gelofusine/gelaspan in people with Medullary Thyroid Carcinoma, run by Paola Anna Erba at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Austria, Germany, Netherlands, Poland, Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CP04 (time frame: 4 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2020.