Colorectal CancerNCT01691391
Early Biomarker With 18F-FDG PET for Treatment Optimization of Anti-EGFR Therapy in Patients With Metastatic Colorectal Cancer.
An observational study of Colorectal Cancer, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
3rd line standard treatment of patients with metastatic colorectal cancer (CRC) harboring K-ras wild type consists of anti-EGFR treatment with either cetuximab or panitumumab. This type of treatment has a modest but significant beneficial activity in this patient group with improved progression-free and overall… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- (Early) Imaging of response with [18F-]-FDG PET-CT and kinase activity profiles
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 46 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2012to 3 Nov 2020
- Phase
- Observational
- 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
Study population: Patients with histopathologically confirmed advanced CRC with K-Ras and BRAF wild type, aged ≥ 18 years, with a life expectancy of at least 12 weeks, who are candidates for anti-EGFR antibody monotherapy (3rd line palliative treatment).
Who may be able to join
- Advanced colorectal adenocarcinoma
- Subjects must have been treated according to standard care with a fluoropyrimidine (e.g. fluorouracil or capecitabine), irinotecan, and oxaliplatin or had contra-indications to treatment with these drugs.
- Age ≥18 years.
- Histological or cytological documentation of cancer is required.
- Tumor material must be tested wild type for the K-Ras gene.
- Subjects have at least one measurable lesion outside the liver. Lesions must be evaluated by CT-scan or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
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- ECOG Performance Status of 0, 1 or 2
- Adequate liver and renal functions as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
- Total bilirubin ≤ 1.5 times the upper limit of normal
- ALT and AST ≤ 2.5 times upper limit of normal (≤ 5 times upper limit of normal for subjects with liver involvement of their cancer)
- Serum creatinin ≤ 1.5 times upper limit of normal or a calculated creatinin clearance ≥ 50 ml/min
- Signed informed consent must be obtained prior to any study specific procedures.
Who cannot join
- Previous exposure to an anti-EGFR therapy
- Significant skin condition interfering with treatment
- Insulin dependency
- Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must agree to use adequate barrier birth control measures (e.g., cervical cap, condom, and diaphragm) during the course of the trial. Oral birth control methods alone will not be considered adequate on this study, because of the potential pharmacokinetic interaction between study drug and oral contraceptives. Concomitant use of oral and barrier contraceptives is advised. Contraception is necessary for at least 6 months after receiving study drug.
- Concurrent anticancer chemotherapy, immunotherapy or investigational drug therapy during the study or within 4 weeks of the start of study drug.
- Radiotherapy to the target lesions during study or within 4 weeks of the start of study drug. Palliative radiotherapy will be allowed.
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- Major surgery within 28 days of start of study drug.
- Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.
- Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
VU University Medical Center
Amsterdam, North Holland, 1081 HV
About this study
Official title: Treatment Optimization of Anti-EGFR Therapy (Cetuximab and Panitumumab) in Patients With Metastatic Colorectal Cancer Based Early 18F-FDG-PET
3rd line standard treatment of patients with metastatic colorectal cancer (CRC) harboring K-ras wild type consists of anti-EGFR treatment with either cetuximab or panitumumab. This type of treatment has a modest but significant beneficial activity in this patient group with improved progression-free and overall survival. Although it is well known that patients with advanced CRC harboring a K-Ras mutation will not respond to anti-EGFR treatment, it is not understood why patients with K-Ras wild type CRC do not all benefit from this type of therapy. In order to optimize treatment of these patients as well as health care costs, it is extremely important to identify those patients who will respond to treatment with an EGFR inhibitor at an early stage.
The investigators hypothesize that the differences in response to treatment with cetuximab are due to variability in the pharmacokinetics and -dynamics of the antibody. Thus, the investigators hypothesize that patients who do not respond to anti-EGFR treatment, have insufficient drug levels in tumor tissue. The investigators hypothesize that this is due to pharmacodynamic processes such as sequestration of cetuximab in the liver which expresses high levels of EGF receptor.
The phase I part of the study was fulfilled after inclusion of 36 patients to evaluate the potential applicability of the 89Zr-cetuximab PET as predictive marker for (absence of) response to cetuximab. Along with this analysis, FDG-PET evaluation before and after 1 administration of cetuximab was being performed. While we observed no correlation of 89Zr-cetuximab tumor uptake with clinical benefit in these 36 patients, we did find a clinical significant predictive value for the absence of response with early 18F-FDG-PET with the lack of clinical benefit at 2 months of treatment in this group of patients. Early 18F-FDG PET response evaluation shows great potential to be a clinically applicable tool to stop an ineffective treatment in a very early phase after one administration of treatment. Such an early predictor is unprecedented in clinical daily practice and will 1) avoid unnecessary toxicity of inactive treatment, 2) will lead to faster prescription of a potentially active alternative treatment and 3) will reduce costs by preventing administration of inactive treatment. In order to provide solid evidence for this new approach, we aim to validate early 18F-FDG-PET as a predictive imaging strategy to identify non-responders in part 2 of the study.
- Conditions
- Colorectal Cancer
- Being tested
- (Early) Imaging of response with [18F-]-FDG PET-CT and kinase activity profiles
- Keywords
- Advanced CRC
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
(Early) Imaging of response with [18F-]-FDG PET-CT and kinase activity profilesBehavioural
Patients will be treated with cetuximab or panitumumab. Two [18F-]-FDG PET-CT will be performed to explore early response. Patients will undergo blood sampling and two skin and tumor biopsies for kinase activity profiles.
| Study group | Role | What they receive |
|---|---|---|
| Advanced CRC, candidates for anti-EGFR antibody monotherapy | Patients with histopathologically confirmed advanced CRC with K-Ras and BRAF wild type, aged ≥ 18 years, with a life expectancy of at least 12 weeks, who are candidates for anti-EGFR antibody monotherapy (3rd line palliative treatment). Receives: Behavioral: (Early) Imaging of response with [18F-]-FDG PET-CT and kinase activity profiles |
What is being measured
The primary outcome is the main question the study is designed to answer.
The predictive value of 18F-FDG-PET for the absence of response compared to the lack of clinical benefit at convential CT at 2 months
The predictive value of 18F-FDG-PET for the absence of response compared to the lack of clinical benefit at convential CT at 2 months
Measured: assessed up to 2 months; date of first CT-scan evaluation
Secondary outcomes (1)
Grade of skin toxicity
Grade of skin toxicity as measured by predefined criteria (see below).
Measured: every 4 weeks until progressive disease
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2012 (estimated)
- Study startJan 2012
- Primary completion3 Nov 2020
- Study completion3 Nov 2020
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 Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Radboud University Medical Center, Jeroen Bosch Ziekenhuis, Leiden University Medical Center, The Netherlands Cancer Institute, Academisch Ziekenhuis Groningen
- Responsible party
- Principal investigator, C. Menke- van der Houven van Oordt, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01691391
- Sponsor's protocol ID
- 2010/323
- Status last verified
- Nov 2020
- First submitted
- 15 May 2012
- Last updated
- 4 Nov 2020
- Results posted
- No
Publications
van Helden EJ, Hoekstra OS, Boellaard R, Roth C, Mulder ER, Verheul HM, Menke-van der Houven van Oordt CW. Early 18F-FDG PET/CT Evaluation Shows Heterogeneous Metabolic Responses to Anti-EGFR Therapy in Patients with Metastatic Colorectal Cancer. PLoS One. 2016 May 19;11(5):e0155178. doi: 10.1371/journal.pone.0155178. eCollection 2016.
PubMed 27196139
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Optimization of Anti-EGFR Therapy (Cetuximab and Panitumumab) in Patients With Metastatic Colorectal Cancer Based Early 18F-FDG-PET
- ClinicalTrials.gov ID
- NCT01691391
- Acronym / sponsor ID
- 2010/323
- Conditions
- Colorectal Cancer
- Keywords
- Advanced CRC
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- Radboud University Medical Center, Jeroen Bosch Ziekenhuis, Leiden University Medical Center, The Netherlands Cancer Institute, Academisch Ziekenhuis Groningen
- Study start
- Jan 2012
- Primary completion
- 3 Nov 2020 (actual)
- Study completion
- 3 Nov 2020 (actual)
- First posted
- 24 Sep 2012 (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.
3rd line standard treatment of patients with metastatic colorectal cancer (CRC) harboring K-ras wild type consists of anti-EGFR treatment with either cetuximab or panitumumab. This type of treatment has a modest but significant beneficial activity in this patient group with improved progression-free and overall survival. Although it is well known that patients with advanced CRC harboring a K-Ras mutation will not respond to anti-EGFR treatment, it is not understood why patients with K-Ras wild type CRC do not all benefit from this type of therapy. In order to optimize treatment of these patients as well as health care costs, it is extremely important to identify those patients who will respond to treatment with an EGFR inhibitor at an early stage.
The investigators hypothesize that the differences in response to treatment with cetuximab are due to variability in the pharmacokinetics and -dynamics of the antibody. Thus, the investigators hypothesize that patients who do not respond to anti-EGFR treatment, have insufficient drug levels in tumor tissue. The investigators hypothesize that this is due to pharmacodynamic processes such as sequestration of cetuximab in the liver which expresses high levels of EGF receptor.
The phase I part of the study was fulfilled after inclusion of 36 patients to evaluate the potential applicability of the 89Zr-cetuximab PET as predictive marker for (absence of) response to cetuximab. Along with this analysis, FDG-PET evaluation before and after 1 administration of cetuximab was being performed. While we observed no correlation of 89Zr-cetuximab tumor uptake with clinical benefit in these 36 patients, we did find a clinical significant predictive value for the absence of response with early 18F-FDG-PET with the lack of clinical benefit at 2 months of treatment in this group of patients. Early 18F-FDG PET response evaluation shows great potential to be a clinically applicable tool to stop an ineffective treatment in a very early phase after one administration of treatment. Such an early predictor is unprecedented in clinical daily practice and will 1) avoid unnecessary toxicity of inactive treatment, 2) will lead to faster prescription of a potentially active alternative treatment and 3) will reduce costs by preventing administration of inactive treatment. In order to provide solid evidence for this new approach, we aim to validate early 18F-FDG-PET as a predictive imaging strategy to identify non-responders in part 2 of the study.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Advanced CRC, candidates for anti-EGFR antibody monotherapy | – | Behavioral: (Early) Imaging of response with [18F-]-FDG PET-CT and kinase activity profilesPatients with histopathologically confirmed advanced CRC with K-Ras and BRAF wild type, aged ≥ 18 years, with a life expectancy of at least 12 weeks, who are candidates for anti-EGFR antibody monotherapy (3rd line palliative treatment). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with histopathologically confirmed advanced CRC with K-Ras and BRAF wild type, aged ≥ 18 years, with a life expectancy of at least 12 weeks, who are candidates for anti-EGFR antibody monotherapy (3rd line palliative treatment).
Key inclusion criteria (12 listed)
- Advanced colorectal adenocarcinoma
- Subjects must have been treated according to standard care with a fluoropyrimidine (e.g. fluorouracil or capecitabine), irinotecan, and oxaliplatin or had contra-indications to treatment with these drugs.
- Age ≥18 years.
- Histological or cytological documentation of cancer is required.
- Tumor material must be tested wild type for the K-Ras gene.
Key exclusion criteria (9 listed)
- Previous exposure to an anti-EGFR therapy
- Significant skin condition interfering with treatment
- Insulin dependency
- Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must agree to use adequate barrier birth control measures (e.g., cervical cap, condom, and diaphragm) during the course of the trial. Oral birth control methods alone will not be considered adequate on this study, because of the potential pharmacokinetic interaction between study drug and oral contraceptives. Concomitant use of oral and barrier contraceptives is advised. Contraception is necessary for at least 6 months after receiving study drug.
- Concurrent anticancer chemotherapy, immunotherapy or investigational drug therapy during the study or within 4 weeks of the start of study drug.
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 |
|---|---|---|
| (Early) Imaging of response with [18F-]-FDG PET-CT and kinase activity profilesPatients will be treated with cetuximab or panitumumab. Two [18F-]-FDG PET-CT will be performed to explore early response. Patients will undergo blood sampling and two skin and tumor biopsies for kinase activity profiles. | Behavioural | Advanced CRC, candidates for anti-EGFR antibody monotherapy |
Primary outcome
The predictive value of 18F-FDG-PET for the absence of response compared to the lack of clinical benefit at convential CT at 2 months
Time frame: assessed up to 2 months; date of first CT-scan evaluation
The predictive value of 18F-FDG-PET for the absence of response compared to the lack of clinical benefit at convential CT at 2 months
1 secondary outcome
Grade of skin toxicity
Time frame: every 4 weeks until progressive disease
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 4 Nov 2020.
- Derived from this study: PubMed 27196139van Helden EJ, Hoekstra OS, Boellaard R, Roth C, Mulder ER, Verheul HM, Menke-van der Houven van Oordt CW. Early 18F-FDG PET/CT Evaluation Shows Heterogeneous Metabolic Responses to Anti-EGFR Therapy in Patients with Metastatic Colorectal Cancer. PLoS One. 2016 May 19;11(5):e0155178. doi: 10.1371/journal.pone.0155178. eCollection 2016.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Colorectal Cancer, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
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 12 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: finished, as of the sponsor's last update on 4 Nov 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 Netherlands. 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.
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?
The predictive value of 18F-FDG-PET for the absence of response compared to the lack of clinical benefit at convential CT at 2 months (time frame: assessed up to 2 months; date of first CT-scan evaluation). 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 NCT01691391, 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 4 Nov 2020.