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

NCT03246659 | Completed Phase 1 DMC

• 1 other identifier: GRAN-T-MTC
• Study Type: interventional
• Target: 16
• Locations: 5 countries
• Sites: 5

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).

Conditions

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

Outcome Measures

Primary Outcomes (4)

• 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

  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

  72 hours from 111In-CP04 injection

• Pharmacokinetics of 111In-CP04

  Area under the selected organs concentration versus time curve

  72 hours from 111In-CP04 injection

• Pharmacokinetics of 111In-CP04

  Area under the blood concentration versus time curve

  72 hours from 111In-CP04 injection

Secondary Outcomes (4)

• Diagnostic sensitivity/specificity of 111In-CP04 to detect cancer lesions

  3 years

• Comparison of pharmacokinetic/imaging effect of low and high peptide amount

  3 years

• Gelofusine/gelaspan injection and CP04 kidney uptake

  3 years

• Dosimetry

  72 hours from 111In-CP04 injection

Study Arms (2)

arm 1

EXPERIMENTAL

111In-CP04

Drug: 111In-CP04

arm 2

EXPERIMENTAL

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

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

Interventions

111In-CP04 DRUG

Radiopharmaceutical preparation

Also known as: 111In-CP04 (DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2

arm 1

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

Radiopharmaceutical preparation with co-administration of gelofusine/gelaspan

Also known as: 111In-CP04 (DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2

arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Paola Anna Erba: lead
• Jagiellonian University: collaborator
• University Hospital Freiburg: collaborator
• Medical University Innsbruck: collaborator
• University Medical Centre Ljubljana: collaborator
• NATIONAL CENTRE FOR NUCLEAR RESEARCH, Poland: collaborator
• Erasmus Medical Center: collaborator
• INRASTES, NCSR Demokritos, Athens, Greece: collaborator

Study Sites (5)

Department of Nuclear Medicine, Innsbruck Medical University

Innsbruck, Austria

Location

Department of Nuclear Medicine, University Hospital Freiburg

Freiburg im Breisgau, Germany

Location

Erasmus University Rotterdam

Rotterdam, Netherlands

Location

Department of Endocrinology, Jagiellonian University Medical College

Krakow, Poland

Location

Department of Nuclear Medicine, University Medical Centre Ljubljana

Ljubljana, Slovenia

Location

Related 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

MeSH Terms

Conditions

Carcinoma, Medullary

Condition Hierarchy (Ancestors)

Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue

Study Officials

• Paola Anna Erba, Professor

  Azienda Ospedaliero, Universitaria Pisana

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 28, 2017
• First Posted: August 11, 2017
• Study Start: August 1, 2016
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: March 20, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1); AU (1); DE (1); NL (1); PL (1)