[18F]-AZAFOL AS POSITRON EMISSION TOMOGRAPHY (PET) TRACER in FR Positive Cancer Imaging

February 27, 2020 updated by: Niklaus Schaefer, University of Lausanne Hospitals

Biodistribution, Tumor Detection, and Radiation Dosimentry of [18F]-AZAFOL as POSITRON EMISSION TOMOGRAPHY (PET) Tracer in Folate Receptor Positive Cancer Imaging

This is a clinical trial category C as this is a first in man trial with an unapproved investigational product. Nevertheless the risk is considered low due to the low dose ≤ 10μg. No toxicity effects were observed preclinically at a dose >1000 -fold the intended dose. Open-labeled, non-blinded, non-placebo controlled, multicenter study.

Primary objective:

Assessment of biodistribution and FR-specific tumor detection of [18F]- AzaFol as a PET imaging agent in patients with FR-positive and FR-negative metastatic cancer of the ovaries or lungs.

Secondary objective:

Calculation of the effective dose to the patient according to the tissue distribution data of [18F]-AzaFol (Dosimetry)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Human research study using a radiopharmaceutical product to reveal folate receptor (FR) expression in tumors in patients.

It is known that the FR is overexpressed on a variety of tumor types. FR-positive tumors can be treated with investigational drugs specifically targeting the FR.

Although the FR-expression status may be determined by immunohistochemical staining of tumor biopsies there is a need for a non-invasive method to determine the presence of the FR on primary tumors and metastases in humans. For this purpose a radiopharmaceutical product will be used as a radiotracer. Positron Emission Tomography (PET) is an imaging method which allows assessing the distribution of radiotracers (called PET tracer). With this imaging method it is possible to obtain (semi)quantitative measures of FR-expression on tumors of at least 4-10 mm diameter in patients.

Such a folate-based radiotracer would be a very helpful tool to non-invasively discriminate FR-positive (often found in ovarian and NSC-lung cancer) from FR-negative tumors in patients with cancer disease as this would allow selecting FR-positive patients amenable to FR-targeted therapies, e.g. folate-targeted antimitotic substances such as EC145 VintafolideTM (Endocyte Inc.) or anti-FR-antibodies such as FarletuzumabTM (Morphotek Inc).

Moreover, [18F]-AzaFol PET could be used for tumor staging and monitoring therapy as well as for follow-up investigations of patients with FR-positive tumors.

Currently there is a radiopharmaceutical product for research purposes available (99mTc-EC20, EtarfolatideTM, Endocyte Inc.) which can be used for Single Photon Emission Computed Tomography (SPECT) imaging. SPECT, however, has multiple limitations compared to PET, such as inferior spatial resolution, soft tissue attenuation, lack of dynamic acquisition etc. Therefore, a PET-compound for FR imaging has been shown to image FR-positive tumors in experimental animals .

Calculations regarding the incidence and mortality of six frequent cancer types in Switzerland indicate that in over 53% of the new cases the FR is expressed (OncoSuisse, Cancer Statistics 2012).

Investigators demonstrate impressively why FR-targeting emerged as an attractive strategy for tumor diagnosis and for the development of new targeted therapy strategies .

The vitamin folic acid (pteroylglutamic acid) emerged as an almost ideal FR-targeting agent because of the high affine binding to the FR (KD < 1 nM).

Due to the small size and vitamin character of folic acid, it is non-immunogenic and non-toxic.

In spite of a large number of folate-based nuclear imaging agents which have been developed in the last two decades only one SPECT radiotracer (99mTc-EC20, EtarfolatideTM) is currently being used in clinical trials in the U.S. for SPECT imaging. For over a decade investigators have been focusing research activities on the development of a 18F-based folate radiotracer for PET imaging (13-16). Recently, a novel folate radiotracer has been developed, 3'-aza-3-[18F]fluorofolic acid (herein referred to as [18F]-AzaFol), for PET imaging purposes.

Compared to SPECT, PET is the more sensitive nuclear imaging method which provides images of an improved resolution and the possibility for accurate quantification of accumulated radioactivity in tumor lesions.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
    • Vaud
      • Lausanne, Vaud, Switzerland, 1011
        • Lausanne University Hospitals

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with cancer of the ovaries (adenocarcinoma) or non-small cell lung cancer (adenocarcinoma, squameous cell cancer or other histology) having active tumor with an indication for a systemic treatment in first or further line.
  • Last systemic treatment should not applied within 3 weeks before performing study exam
  • Male and female patients 18 years and older,
  • Voluntarily signed Informed Consent after being informed

Inclusion criteria for [18F]-AzaFol PET (enrollment into study):

  • FR-positive histology in routinely acquired biopsy samples (30 Patients)
  • FR-negative histology in routinely acquired biopsy samples (6 Patients)

Exclusion Criteria:

  • contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product,
  • women who are pregnant or breast feeding,
  • women with the intention to become pregnant during the course of the study,
  • other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease),
  • Renal clearance < 60 mL/min; liver transaminases ≥ 3-fold increased; bilirubin > 1.5-fold increased; Hb < 8 g/dl; Tc < 100'000, ANC < 1'500/ul
  • ECOG 3-4
  • known or suspected non-compliance, drug or alcohol abuse,
  • inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the subject,
  • Participation in another study with an investigational drug during the present study and 7 days thereafter.
  • Enrolment of the investigator, his family members, employees and other dependent persons

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: treatment group

all patients successfully enrolled will be assigned to the treatment group:

1 mg folic acid (corresponding to 0.2 mL Folarell®) will be injected 5 min prior to [18F]-AzaFol
Drug: [18F]-AzaFol
[18F]-AzaFol is a radiotracer produced at ETH Hönggerberg in a radiopharmaceutical GMP facility. The drug product is provided as sterile solution for intravenous injection in a glass vial containing 6 mL of formulated product, the maximal applicable dose being 600 MBq.
Drug: folarell

For the purpose of this study only 1 mg folic acid (corresponding to 0.2 mL Folarell®) will be injected 5 min prior to [18F]-AzaFol. Due to this low dose of a single injection of folic acid it is unlikely that adverse events would occur.

Folarell® is a folic acid preparation for intravenous or intramuscular injection

Other Names:
  • folic acid

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
SUV values and volume of tracer uptake of all suspected positive lesions
Time Frame: day 0

SUVmax g/ml SUVmean42% g/ml

lesion seen on SOC : mm
day 0
Potential change of overall staging
Time Frame: day 0
TNM staging
day 0
Lesion detection rate in comparison to SOC (CT and/or MR and/or FDG performed within 4 weeks of PET imaging).
Time Frame: day 0
% (percentage)
day 0
Estimation of gained information using this tracer
Time Frame: day 0
uptake yes / no
day 0
quantitative estimations
Time Frame: day 0
SUV values for ROC analysis g/ml
day 0
General estimation of gained confidence in changing/adapting therapy based on this image
Time Frame: day 0
continuous % variable of confidence
day 0
Available biopsy results can be used as further variables to better assess the performance of [18F]-AzaFol
Time Frame: day 0
+ / - ( positive or negative)
day 0

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Calculation of the effective dose to the patient according to the tissue distribution data of [18F]-AzaFol (Dosimetry)
Time Frame: day 0
The secondary outcome is the calculated tissue distribution data of [18F]-AzaFol obtained in humans. The effective dose for all organs will be calculated using the OLINDA software (version 1.0). The data will be compared to the estimated data from our preclinical data set. This will provide the radiation dosimetry values as well as quantitative biodistribution over all relevant organs.
day 0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Lausanne Hospitals

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University Hospital, Zürich
Cantonal Hospital of St. Gallen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: John Prior, Prof, Lausanne University Hospitals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 20, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 7, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 8, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 28, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 27, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PET - FOL - I

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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Conditions

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