Metastasising Cancer of Unknown PrimaryPhase 4NCT01469026
CUP Project PET/CT
A Phase 4 study testing PET/CT or Conventional diagnostics including CT in people with Metastasising Cancer of Unknown Primary, run by Odense University Hospital at 1 site in Denmark.
Trial summary
The purpose is to elucidate the value of PET/CT applied early in the work-up of patients with a metastasising cancer of an unknown primary tumor. The management of patients with metastasising cancer of unknown primary often includes various and a large number of radiographic studies and invasive procedures, but the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastasising Cancer of Unknown Primary
- What is being tested?
- PET/CT or Conventional diagnostics including CT
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 1 siteDenmark
- Study dates
- Nov 2011to Dec 2014
- Phase
- Phase 4
- 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
- Biopsy proven cancer without identified origin at the time of examination.
- Patients admitted to but not fitting into existing cancer package programs.
- Patients with very serious, but unknown, disease, which might be cancer.
Who cannot join
- Patient belongs to one of the existing cancer packages - state which one.
- Suspected metastasis in the liver.
- Suspected metastasis in the brain.
- Prior PET/CT imaging showing multiple metastases with no identifiable primary.
- Cancer treatment already started.
- Estimated inability to collaborate - state reason.
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- Prior malignant disease.
- Pregnancy.
- The patient cannot read and understand Danish.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Depatment of Nuclearmedicine
Odense, 5000
Charlotte Rask, Medical doctor, (+45)30161459, charlotte.rask@ouh.regionsyddanmark.dk
Charlotte Rask, Medical doctor
About this study
Official title: The Value of Early PET/CT in Patients With Metastasising Cancer of Unknown Primary
The purpose is to elucidate the value of PET/CT applied early in the work-up of patients with a metastasising cancer of an unknown primary tumor.
The management of patients with metastasising cancer of unknown primary often includes various and a large number of radiographic studies and invasive procedures, but the occult primary tumor is detected in less than 20%.
Early PET/CT may be useful in Cancer of Unknown Primary (CUP) before expensive and invasive diagnostic procedures are carried out. The outcome may be higher tumor detection rate and quicker diagnosis, avoiding unnecessary, extensive procedures. Furthermore, a large number of the patients will receive treatment aimed at the correct diagnosis. Therefore, a prospective cost-effectiveness analysis is warranted.
Read the detailed description
Background:
Every year, 800-1000 patients in Denmark are classified with a diagnosis of metastasising cancer of unknown primary (CUP). This corresponds to approximately 3 % percent of all new cancer cases on a national scale. The number is probably higher, since this is a heterogeneous group of patients that is not registered consistently. The prognosis is poor; the average survival is only approximately one year.
CUP is characterized by the finding of a metastasis the starting point of which (the primary tumour) is unknown. Typically, one finds an enlarged lymph node in the neck, a swelling in the throat or in the stomach, a filling in the skin or a tumour detected somewhere in the body during an X-Ray examination, an endoscopy or the like. In spite of a search applying multiple techniques, the primary tumour remains unknown in 70-80% of the patients.
A great number of patients experience a long and discontinuous examination sequence marked by various contacts with doctors, many examinations dispersed over many days and locations, as well as a lot of time wasted, because there exists no single option or institution that takes care of the patient and handles diagnostic procedures and treatment efficiently.
Treatment is often initiated too late, typically as a combination of several chemotherapeutics in order to cover different types of cancer simultaneously, but modern chemotherapeutical regimes have not increased the survival rate. The bad prognosis is undoubtedly due to the fact that the patients are diagnosed in an advanced phase. Alternatively, the primary tumour is not detected at all. This, in part, is due to the absence of any single agency in possession of the competence and responsibility to implement the work-up without delay, and maybe because one does not offer examination by the modality (PET/CT) which is most likely to detect the presence of cancer, its starting point and dispersion in an early stage.
Methods:
Patients will be randomized 1:1 to the diagnostic arms 'conventional diagnostics incl. CT' or 'early PET/CT' at study entry. Before study start, a randomization list will be prepared according to which the assignment of patients to the treatment arms will be performed.
The early PET/CT examination will be performed at the Department of Nuclear Medicine at Odense University Hospital (OUH) using the tracer [18F]-fluorodeoxyglucose (FDG). Patients will be requested to appear in fasting state (minimum 6 hours) and will be administered intravenously FDG which is a radioactively labeled glucose-analog which enters cells by known glucose transport systems. The usage of FDG as cancer tracer is based on the increased metabolism and glucose demand of rapidly growing and proliferating cells. FDG remains within cells since it does not metabolize.
The patients will be scanned from the base of the scull to mid thigh by an integrated PET/CT scanner (GE Healthcare DiscoveryTM STE). A standardized CT protocol is used (Smart mA 30-400 mA with a noise index of 18.0 and rotation time of 0.8 s., kV 120, reconstruction thickness of 3.75 mm), followed by a PET examination (recording time is 2.5 min pr. field of view). CT scanning will be done with intravenous contrast medium (Ultravist 370 mg I/ml). The effective dose will be 18-20 mSv from CT and 5-6 mSv from FDG PET. Every patient at the Department of Nuclear Medicine has their height and weight measured before PET/CT and the PET/CT examination must be started in the interval 60 ± 5 min. after injection of FDG. Serum glucose concentration is measured before injection of FDG and must not exceed 8 mmol/L (150 mg/dL) The first 40 patients with a negative FDG-PET/CT will have an extra, late scan (without new contrast and with the same FDG-injection). One half (20 patients) will be scanned after 3 hours and the second half (20 patients) will be scanned 4 hours after the injection of FDG. This is to examine whether there is late focal uptake in some patients due to slow and only slightly increased glucose uptake. If so, the standard time point of scanning will in the remaining patients be at 3 or 4 hours after the injection of FDG in order to optimize the chance of detecting also slow growing tumours and metastases.
Identification of the primary tumor:
The primary tumor will be confirmed by histopathological examination of relevant biopsy specimens.
Endpoints:
In order to evaluate the hypotheses, the following data will be collected for all patients retrospectively from the local patient report filing system FPAS:
- Detection of primary tumor possible: yes/no (primary endpoint)
- Time frame from inclusion into the study to detection of primary tumor.
- Time frame from inclusion into the study to referral to palliative or curative treatment.
- Time frame from inclusion into the study to end of follow-up or death.
- Total score of Quality of Life instrument "SF-36".
Population:
All patients are recruited from the Emergency Department based on subjective selection at the discretion of a trained internal medicine specialist (KKP). The expected number of patients will be 220.
Ethics:
The risk of PET/CT consists in the extra radiation dose (5-6mSv, p 4), which the PET-examination adds to the patient beyond the dose from CT (18-20mSv). The dose of radiation from PET is insignificant (a total estimated risk: 1/10.000), while the estimated risk from the radiation dose of CT is 1/1000. The lifetime risk of developing cancer is 25%. Performing the PET/CT scan increases the lifetime risk from 25% to 25,1%.
The radiation dose which is used has never been proven to cause adverse effects. The increase in lifetime effect is considered acceptable when compared to the improvement in diagnostic yield, patient course and targeted treatment.
Patient information describing the study and providing sufficient information for patients to make an informed decision about their participation will be handed out to patients in written form.
The patients will have 24 hours to think it over before making the final decision whether or not to participate. Participation is voluntary and consent can at anytime be withdrawn without any consequences for the patient's future treatment.
The Informed Consent form will be signed by all participating patients and stored at the Department of Nuclear Medicine
- Conditions
- Metastasising Cancer of Unknown Primary
- Being tested
- PET/CT or Conventional diagnostics including CT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET/CT or Conventional diagnostics including CTRadiation
Also called Radiation:, Positron emission tomography, Computed tomography
Radiation:
PET/CT. 4 MBq/kg (max. 400 MBq) 18F-flour-deoxyglucosegiven iv. 60 min. before PET/CT scan.
CT. iv.contrast medium (Ultravist 370 mg I/ml).
| Study group | Role | What they receive |
|---|---|---|
| Early PET/CT | Active comparator | Not described Receives: Radiation: PET/CT or Conventional diagnostics including CT |
| Conventional diagnostics including CT | Active comparator | Not described Receives: Radiation: PET/CT or Conventional diagnostics including CT |
What is being measured
The primary outcome is the main question the study is designed to answer.
1. Detection of primary tumor possible: yes/no (primary endpoint)
The outcome is evaluated based on the project specified PET/CT compared to conventional diagnostic investigations including CT. - The evaluation of the PET/CT scan, primary tumor/non-primary tumor, is obtained by consensus of two nuclear medicine physicians with experience in PET/CT.
Measured: Up to 24 hours
Secondary outcomes (4)
2. Time frame from inclusion into the study to detection of primary tumor.
The time frame is determined by the number of days from the date of inclusion to the date of description for the PET/CT or the date of description for conventional CT.
Measured: Up to 1 week
3. Time frame from inclusion into the study to referral to palliative or curative treatment.
The time frame is determined by the number of days from the date of inclusion to the date of description for the PET/CT or the date of description for conventional CT.
Measured: Up to 4 weeks
4. Time frame from inclusion into the study to end of follow-up or death.
Patients are followed till death or 36 months post inclusion.
Measured: 36 months
5. Total score of Quality of Life instrument "SF-36".
Quality of life evaluation is performed at 3-6-12 and 36 months.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2011 (estimated)
- Study startNov 2011
- Primary completionDec 2013 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastasising Cancer of Unknown PrimaryStudies 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 4
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Odense University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Charlotte Krogh Rask, Odense University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01469026
- Sponsor's protocol ID
- K36
- Status last verified
- Nov 2011
- First submitted
- 28 Oct 2011
- Last updated
- 10 Nov 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Value of Early PET/CT in Patients With Metastasising Cancer of Unknown Primary
- ClinicalTrials.gov ID
- NCT01469026
- Acronym / sponsor ID
- K36
- Conditions
- Metastasising Cancer of Unknown Primary
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- Odense University HospitalUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 10 Nov 2011 (estimated)
- 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 purpose is to elucidate the value of PET/CT applied early in the work-up of patients with a metastasising cancer of an unknown primary tumor.
The management of patients with metastasising cancer of unknown primary often includes various and a large number of radiographic studies and invasive procedures, but the occult primary tumor is detected in less than 20%.
Early PET/CT may be useful in Cancer of Unknown Primary (CUP) before expensive and invasive diagnostic procedures are carried out. The outcome may be higher tumor detection rate and quicker diagnosis, avoiding unnecessary, extensive procedures. Furthermore, a large number of the patients will receive treatment aimed at the correct diagnosis. Therefore, a prospective cost-effectiveness analysis is warranted.
Detailed description
Background:
Every year, 800-1000 patients in Denmark are classified with a diagnosis of metastasising cancer of unknown primary (CUP). This corresponds to approximately 3 % percent of all new cancer cases on a national scale. The number is probably higher, since this is a heterogeneous group of patients that is not registered consistently. The prognosis is poor; the average survival is only approximately one year.
CUP is characterized by the finding of a metastasis the starting point of which (the primary tumour) is unknown. Typically, one finds an enlarged lymph node in the neck, a swelling in the throat or in the stomach, a filling in the skin or a tumour detected somewhere in the body during an X-Ray examination, an endoscopy or the like. In spite of a search applying multiple techniques, the primary tumour remains unknown in 70-80% of the patients.
A great number of patients experience a long and discontinuous examination sequence marked by various contacts with doctors, many examinations dispersed over many days and locations, as well as a lot of time wasted, because there exists no single option or institution that takes care of the patient and handles diagnostic procedures and treatment efficiently.
Treatment is often initiated too late, typically as a combination of several chemotherapeutics in order to cover different types of cancer simultaneously, but modern chemotherapeutical regimes have not increased the survival rate. The bad prognosis is undoubtedly due to the fact that the patients are diagnosed in an advanced phase. Alternatively, the primary tumour is not detected at all. This, in part, is due to the absence of any single agency in possession of the competence and responsibility to implement the work-up without delay, and maybe because one does not offer examination by the modality (PET/CT) which is most likely to detect the presence of cancer, its starting point and dispersion in an early stage.
Methods:
Patients will be randomized 1:1 to the diagnostic arms 'conventional diagnostics incl. CT' or 'early PET/CT' at study entry. Before study start, a randomization list will be prepared according to which the assignment of patients to the treatment arms will be performed.
The early PET/CT examination will be performed at the Department of Nuclear Medicine at Odense University Hospital (OUH) using the tracer [18F]-fluorodeoxyglucose (FDG). Patients will be requested to appear in fasting state (minimum 6 hours) and will be administered intravenously FDG which is a radioactively labeled glucose-analog which enters cells by known glucose transport systems. The usage of FDG as cancer tracer is based on the increased metabolism and glucose demand of rapidly growing and proliferating cells. FDG remains within cells since it does not metabolize.
The patients will be scanned from the base of the scull to mid thigh by an integrated PET/CT scanner (GE Healthcare DiscoveryTM STE). A standardized CT protocol is used (Smart mA 30-400 mA with a noise index of 18.0 and rotation time of 0.8 s., kV 120, reconstruction thickness of 3.75 mm), followed by a PET examination (recording time is 2.5 min pr. field of view). CT scanning will be done with intravenous contrast medium (Ultravist 370 mg I/ml). The effective dose will be 18-20 mSv from CT and 5-6 mSv from FDG PET. Every patient at the Department of Nuclear Medicine has their height and weight measured before PET/CT and the PET/CT examination must be started in the interval 60 ± 5 min. after injection of FDG. Serum glucose concentration is measured before injection of FDG and must not exceed 8 mmol/L (150 mg/dL) The first 40 patients with a negative FDG-PET/CT will have an extra, late scan (without new contrast and with the same FDG-injection). One half (20 patients) will be scanned after 3 hours and the second half (20 patients) will be scanned 4 hours after the injection of FDG. This is to examine whether there is late focal uptake in some patients due to slow and only slightly increased glucose uptake. If so, the standard time point of scanning will in the remaining patients be at 3 or 4 hours after the injection of FDG in order to optimize the chance of detecting also slow growing tumours and metastases.
Identification of the primary tumor:
The primary tumor will be confirmed by histopathological examination of relevant biopsy specimens.
Endpoints:
In order to evaluate the hypotheses, the following data will be collected for all patients retrospectively from the local patient report filing system FPAS:
- Detection of primary tumor possible: yes/no (primary endpoint)
- Time frame from inclusion into the study to detection of primary tumor.
- Time frame from inclusion into the study to referral to palliative or curative treatment.
- Time frame from inclusion into the study to end of follow-up or death.
- Total score of Quality of Life instrument "SF-36".
Population:
All patients are recruited from the Emergency Department based on subjective selection at the discretion of a trained internal medicine specialist (KKP). The expected number of patients will be 220.
Ethics:
The risk of PET/CT consists in the extra radiation dose (5-6mSv, p 4), which the PET-examination adds to the patient beyond the dose from CT (18-20mSv). The dose of radiation from PET is insignificant (a total estimated risk: 1/10.000), while the estimated risk from the radiation dose of CT is 1/1000. The lifetime risk of developing cancer is 25%. Performing the PET/CT scan increases the lifetime risk from 25% to 25,1%.
The radiation dose which is used has never been proven to cause adverse effects. The increase in lifetime effect is considered acceptable when compared to the improvement in diagnostic yield, patient course and targeted treatment.
Patient information describing the study and providing sufficient information for patients to make an informed decision about their participation will be handed out to patients in written form.
The patients will have 24 hours to think it over before making the final decision whether or not to participate. Participation is voluntary and consent can at anytime be withdrawn without any consequences for the patient's future treatment.
The Informed Consent form will be signed by all participating patients and stored at the Department of Nuclear Medicine
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early PET/CT | Active comparator | Radiation: PET/CT or Conventional diagnostics including CT |
| Conventional diagnostics including CT | Active comparator | Radiation: PET/CT or Conventional diagnostics including CT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Biopsy proven cancer without identified origin at the time of examination.
- Patients admitted to but not fitting into existing cancer package programs.
- Patients with very serious, but unknown, disease, which might be cancer.
Key exclusion criteria (9 listed)
- Patient belongs to one of the existing cancer packages - state which one.
- Suspected metastasis in the liver.
- Suspected metastasis in the brain.
- Prior PET/CT imaging showing multiple metastases with no identifiable primary.
- Cancer treatment already started.
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 |
|---|---|---|
| PET/CT or Conventional diagnostics including CTAlso: Radiation:, Positron emission tomography, Computed tomographyRadiation: PET/CT. 4 MBq/kg (max. 400 MBq) 18F-flour-deoxyglucosegiven iv. 60 min. before PET/CT scan. CT. iv.contrast medium (Ultravist 370 mg I/ml). | Radiation | Conventional diagnostics including CT, Early PET/CT |
Primary outcome
1. Detection of primary tumor possible: yes/no (primary endpoint)
Time frame: Up to 24 hours
The outcome is evaluated based on the project specified PET/CT compared to conventional diagnostic investigations including CT. - The evaluation of the PET/CT scan, primary tumor/non-primary tumor, is obtained by consensus of two nuclear medicine physicians with experience in PET/CT.
4 secondary outcomes
2. Time frame from inclusion into the study to detection of primary tumor.
Time frame: Up to 1 week
3. Time frame from inclusion into the study to referral to palliative or curative treatment.
Time frame: Up to 4 weeks
4. Time frame from inclusion into the study to end of follow-up or death.
Time frame: 36 months
5. Total score of Quality of Life instrument "SF-36".
Time frame: 36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2011.
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing PET/CT or Conventional diagnostics including CT in people with Metastasising Cancer of Unknown Primary, run by Odense University Hospital at 1 site in Denmark.
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 3 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 10 Nov 2011. 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 Denmark. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Charlotte Rask, Medical Doctor ((+45) 30161459, charlotte.rask@ouh.regionsyddanmark.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1. Detection of primary tumor possible: yes/no (primary endpoint) (time frame: Up to 24 hours). 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 10 Nov 2011; AzTrials last refreshed its copy on 1 Nov 2026.