Metastatic Cancer LungPhase 1NCT03242993
[18F]-AZAFOL AS POSITRON EMISSION TOMOGRAPHY (PET) TRACER in FR Positive Cancer Imaging
A Phase 1 study testing [18F]-AzaFol and folarell in people with Metastatic Cancer Lung and Metastatic Ovarian Cancer, run by University of Lausanne Hospitals at 1 site in Switzerland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Cancer Lung, Metastatic Ovarian Cancer
- What is being tested?
- [18F]-AzaFol and folarell
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Apr 2017to 1 Jun 2019
- 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
- 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)
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Lausanne University Hospitals
Lausanne, Canton of Vaud, 1011
About this study
Official title: 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)
Read the 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.
- Conditions
- Metastatic Cancer Lung, Metastatic Ovarian Cancer
- Being tested
- [18F]-AzaFol, folarell
- Medical subject headings
- Lung Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]-AzaFolDrug
[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.
folarellDrug
Also called folic acid
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
| Study group | Role | What they receive |
|---|---|---|
| treatment group | Experimental | 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 Receives: Drug: [18F]-AzaFol; Drug: folarell |
What is being measured
The primary outcome is the main question the study is designed to answer.
SUV values and volume of tracer uptake of all suspected positive lesions
SUVmax g/ml SUVmean42% g/ml
lesion seen on SOC : mm
Measured: day 0
Potential change of overall staging
TNM staging
Measured: day 0
Lesion detection rate in comparison to SOC (CT and/or MR and/or FDG performed within 4 weeks of PET imaging).
% (percentage)
Measured: day 0
Estimation of gained information using this tracer
uptake yes / no
Measured: day 0
quantitative estimations
SUV values for ROC analysis g/ml
Measured: day 0
General estimation of gained confidence in changing/adapting therapy based on this image
continuous % variable of confidence
Measured: day 0
Available biopsy results can be used as further variables to better assess the performance of [18F]-AzaFol
+ / - ( positive or negative)
Measured: day 0
Secondary outcomes (1)
Calculation of the effective dose to the patient according to the tissue distribution data of [18F]-AzaFol (Dosimetry)
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.
Measured: day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2017
- Study start1 Apr 2017
- Primary completion1 Jun 2019
- Study completion1 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Cancer LungStudies 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a single arm study. No placebo or other comparator will be used. \[18F\]-AzaFol is used as a PET tracer, all patients successfully enrolled will be assigned to the treatment group.
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Lausanne Hospitals
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Zürich, Cantonal Hospital of St. Gallen
- Responsible party
- Principal investigator, Niklaus Schaefer, University of Lausanne Hospitals
- Investigators
- John Prior, Prof, Principal investigator, Lausanne University Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03242993
- Sponsor's protocol ID
- PET - FOL - I
- Status last verified
- Feb 2020
- First submitted
- 20 Jul 2017
- Last updated
- 28 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Gnesin S, Muller J, Burger IA, Meisel A, Siano M, Fruh M, Choschzick M, Muller C, Schibli R, Ametamey SM, Kaufmann PA, Treyer V, Prior JO, Schaefer N. Radiation dosimetry of 18F-AzaFol: A first in-human use of a folate receptor PET tracer. EJNMMI Res. 2020 Apr 8;10(1):32. doi: 10.1186/s13550-020-00624-2.
PubMed 32270313
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biodistribution, Tumor Detection, and Radiation Dosimentry of [18F]-AZAFOL as POSITRON EMISSION TOMOGRAPHY (PET) Tracer in Folate Receptor Positive Cancer Imaging
- ClinicalTrials.gov ID
- NCT03242993
- Acronym / sponsor ID
- PET - FOL - I
- Conditions
- Metastatic Cancer Lung, Metastatic Ovarian Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of Lausanne HospitalsUniversity, hospital or other
- Collaborators
- University Hospital, Zürich, Cantonal Hospital of St. Gallen
- Study start
- 1 Apr 2017 (actual)
- Primary completion
- 1 Jun 2019 (actual)
- Study completion
- 1 Jun 2019 (actual)
- First posted
- 8 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.
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)
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single arm study. No placebo or other comparator will be used. [18F]-AzaFol is used as a PET tracer, all patients successfully enrolled will be assigned to the treatment group.
| Arm | Type | Receives |
|---|---|---|
| treatment group | Experimental | Drug: [18F]-AzaFol, Drug: folarellall 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
- FR-positive histology in routinely acquired biopsy samples (30 Patients)
Key exclusion criteria (10 listed)
- 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
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 |
|---|---|---|
| [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 | treatment group |
| folarellAlso: folic acidFor 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 | Drug | treatment group |
Primary outcome
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
Potential change of overall staging
Time frame: day 0
TNM staging
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)
Estimation of gained information using this tracer
Time frame: day 0
uptake yes / no
quantitative estimations
Time frame: day 0
SUV values for ROC analysis g/ml
General estimation of gained confidence in changing/adapting therapy based on this image
Time frame: day 0
continuous % variable of confidence
Available biopsy results can be used as further variables to better assess the performance of [18F]-AzaFol
Time frame: day 0
+ / - ( positive or negative)
1 secondary outcome
Calculation of the effective dose to the patient according to the tissue distribution data of [18F]-AzaFol (Dosimetry)
Time frame: day 0
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 28 Feb 2020.
- Derived from this study: PubMed 32270313Gnesin S, Muller J, Burger IA, Meisel A, Siano M, Fruh M, Choschzick M, Muller C, Schibli R, Ametamey SM, Kaufmann PA, Treyer V, Prior JO, Schaefer N. Radiation dosimetry of 18F-AzaFol: A first in-human use of a folate receptor PET tracer. EJNMMI Res. 2020 Apr 8;10(1):32. doi: 10.1186/s13550-020-00624-2.
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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.
John Prior, Prof principal investigator
Lausanne University Hospitals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing [18F]-AzaFol and folarell in people with Metastatic Cancer Lung and Metastatic Ovarian Cancer, run by University of Lausanne Hospitals at 1 site in Switzerland.
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 7 inclusion and 10 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 28 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. 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?
SUV values and volume of tracer uptake of all suspected positive lesions (time frame: day 0). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03242993, which also lists 1 linked publication.
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 28 Feb 2020.