Supratentorial Newly Diagnosed Inoperable GliobastomaPhase 1NCT01558687
Cilengitide Imaging Trial in Glioblastoma
A Phase 1 study testing Standard therapy in people with Supratentorial Newly Diagnosed Inoperable Gliobastoma, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.
Trial summary
The main purpose of this clinical trial is to find out if cilengitide has an effect on brain tumor cells but also particularly on the blood vessels supplying the tumor with nutrient and oxygen in patients newly diagnosed with non-resectable (inoperable) glioblastoma. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Supratentorial Newly Diagnosed Inoperable Gliobastoma
- What is being tested?
- Standard therapy
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2012to Feb 2013
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subject aged ≥ 18 to ≤ 70 years at the time of informed consent signature
- Tumor tissue specimens taken from multimodal imaging-guided stereotactic biopsy must be available for histopathological confirmation of GBM and potential subsequent analysis of tissue molecular markers
- Newly diagnosed histologically proven supratentorial GBM (World Health Organization [WHO] Grade IV)
- Subject with non-resectable GBM
- Available dynamic MRI and FET-PET scan prior to randomization
- Available Gd-MRI performed prior randomization
Show all 9Show fewer
- ECOG Performance status of 0-2
- Stable or decreasing dose of steroids for >= 5 days prior to randomization
- Given written informed consent
Who cannot join
- Prior chemotherapy within the last 5 years
- Prior RTX of the head (except for low-dose radiotherapy for Tinea capitis)
- Gross total resection/partial resection (GBM surgery), placement of Gliadel® wafer
- Receiving concurrent investigational agents or receipt of an investigational agent within the past 30 days prior to the first day of intensified imaging (W1D1)
- Prior systemic antiangiogenic therapy
- Inability to undergo dynamic MR or FET-PET imaging
Show all 12Show fewer
- History of allergic reactions attributed to Gadolinium-based contrast agents for MRI, compounds of similar chemical or biological composition
- Planned major surgery for other diseases
- History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months prior to enrollment
- History of other malignant disease or acute malignant disease. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for ≥ 5 years are eligible for this study
- Current or history of bleeding disorders and/or history of thromboembolic events
- Clinically manifest myocardial insufficiency (NYHA III, IV) or history of myocardial infarction during the past 6 months prior to enrollment, uncontrolled arterial hypertension
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multi-center, Open-label, Randomized, Controlled Phase I Trial to Investigate the Effects of Cilengitide (EMD 121974) Using Dynamic MR and FET-PET Imaging as a Pharmacodynamic Measure of Response in Subjects With Newly Diagnosed Glioblastoma
The main purpose of this clinical trial is to find out if cilengitide has an effect on brain tumor cells but also particularly on the blood vessels supplying the tumor with nutrient and oxygen in patients newly diagnosed with non-resectable (inoperable) glioblastoma.
In addition, this clinical trial will investigate if the addition of cilengitide in combination with standard treatment prolongs life in patients with non-resectable glioblastoma. Similarly, the duration of response of the cancer to this treatment and the side effects of the therapy will be analyzed. Furthermore, additional data on how the body deals with this substance will be collected (this is called pharmacokinetics or pharmacokinetic (PK) analysis). In this clinical trial the investigators would also like to learn more about the disease and the response to the experimental medication by measuring certain "markers".
Read more
This imaging trial will investigate the biological effects of cilengitide monotherapy on the tumor microvascular function and tumor viability in a homogenous non-pretreated subject population with newly diagnosed Gliobastoma (GBM). The purpose of this clinical trial is to study the effect that cilengitide may have on certain markers of cancer in your tumor and/or blood and to learn if there are any disease-related markers that could help in predicting how subjects respond to the administration of cilengitide.
The investigators anticipate that approximately 30 subjects will participate in this clinical trial. The clinical trial will be conducted in approximately 4 medical centers in the following countries: Germany, Poland, and Switzerland. The investigators anticipate the clinical trial will last until the end of 2013. Your participation in the trial may last up to 86 weeks.
- Being tested
- Drug (including placebo), Standard therapy
- Keywords
- Oncology, newly diagnosed inoperable glioblastoma, temolozomide, radiotherapy, dynamic MRI, Positron emission tomography, [18]FET tracer, cilengitide, World Health Organization [WHO] Grade IV
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drug (including placebo)Drug
Subjects will receive cilengitide monotherapy for 2 weeks (Weeks 1 and 2); thereafter, cilengitide will be given in combination with the standard treatment regimen during Weeks 3 to 36. The standard combination treatment of radiotherapy (RTX) plus Temolozomide (TMZ) will be administered for a maximum of 6 weeks (Weeks 3 to 8), followed by TMZ maintenance treatment starting 4 weeks after RTX (i.e., Week 13) for up to 6 cycles, 4 weeks per cycle.
Cilengitide monotherapy treatment will be given to subjects in Group A for another 10 months as maintenance treatment (Weeks 37 to 78). Subjects in Group A may continue to receive cilengitide maintenance treatment beyond 10 months (beyond Week 78) until occurrence of progressive disease (PD) or unacceptable toxicity, or withdrawal for any other reason. A 28-day safety follow-up will be performed after the last dose of cilengitide.
Standard therapyOther
In the first two weeks, treatment of subjects in Group B will be in line with the SoC. Thereafter the standard combination treatment of radiotherapy (RTX) plus Temolozomide (TMZ) will be administered for a maximum of 6 weeks (Weeks 3 to 8), followed by TMZ maintenance treatment starting 4 weeks after RTX (i.e., Week 13) for up to 6 cycles, 4 weeks per cycle.
| Study group | Role | What they receive |
|---|---|---|
| Group A = Cilengitide Group | Experimental | Cilengitide + SoC (Temolozomide + Radiotherapy) Receives: Drug: Drug (including placebo) |
| Group B = Control Group | Active comparator | SoC (Temolozomide + Radiotherapy) Receives: Other: Standard therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate constant for passive contrast agent plasma/interstitium transfer (ktrans)
Any change in tumor kinetic model parameter (maximum increase in ktrans) to assess the tumor microvasculature structure and function
Measured: 2 weeks
Fractional blood plasma volume (vp)
Any change in tumor kinetic model parameter (maximum change in vp) to assess the tumor microvasculature structure and function
Measured: 2 weeks
Maximum tumor to brain ratio (TBRmax)
Assessment of tumor amino acid (FET) uptake (tumor viability)
Measured: 2 weeks
Secondary outcomes (6)
Total tumor volume and enhancing tumor volume
Change in total tumor volume and enhancing tumor volume as a measure of the overall level of tumor perfusion during the first 2 weeks of treatment with Cilengitide monotherapy
Measured: 2 weeks
Interstitial space volume fraction (putative contrast agent distribution volume) (=ve)
Change in the tumor extravascular extracellular space volume during the first 2 weeks of treatment with Cilengitide monotherapy
Measured: 2 weeks
Apparent Diffusion coefficient (ADC)
Change in perfusion parameter ADC during the first 2 weeks of treatment with Cilengitide monotherapy
Measured: 2 weeks
Fractional anisotropy (FA)
Change in FA during the first 2 weeks of treatment with Cilengitide monotherapy
Measured: 2 weeks
Kinetic behavior of [18F]FET uptake
Change in tumor amino acid (FET) uptake kinetics during the first 2 weeks of treatment with Cilengitide monotherapy
Measured: 2 weeks
Mean spin-lattice relaxation time of unbound protons in water
Change in Absolute T1(mean spin-lattice relaxation time of unbound protons in water) during the first 2 weeks of treatment with Cilengitide monotherapy
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2012 (estimated)
- Study startAug 2012
- Primary completionFeb 2013
- Study completionFeb 2013
Why it stopped: Discontinuation of development program
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Supratentorial Newly Diagnosed Inoperable GliobastomaStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ute Klinkhardt, MD, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01558687
- Sponsor's protocol ID
- EMR062041-017
- Other IDs
- 2011-003794-29
- Status last verified
- Feb 2014
- First submitted
- 16 Mar 2012
- Last updated
- 4 Feb 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Open-label, Randomized, Controlled Phase I Trial to Investigate the Effects of Cilengitide (EMD 121974) Using Dynamic MR and FET-PET Imaging as a Pharmacodynamic Measure of Response in Subjects With Newly Diagnosed Glioblastoma
- ClinicalTrials.gov ID
- NCT01558687
- Acronym / sponsor ID
- EMR062041-017
- Keywords
- Oncology, newly diagnosed inoperable glioblastoma, temolozomide, radiotherapy, dynamic MRI, Positron emission tomography, [18]FET tracer, cilengitide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Discontinuation of development program
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- Aug 2012
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 20 Mar 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.
The main purpose of this clinical trial is to find out if cilengitide has an effect on brain tumor cells but also particularly on the blood vessels supplying the tumor with nutrient and oxygen in patients newly diagnosed with non-resectable (inoperable) glioblastoma.
In addition, this clinical trial will investigate if the addition of cilengitide in combination with standard treatment prolongs life in patients with non-resectable glioblastoma. Similarly, the duration of response of the cancer to this treatment and the side effects of the therapy will be analyzed. Furthermore, additional data on how the body deals with this substance will be collected (this is called pharmacokinetics or pharmacokinetic (PK) analysis). In this clinical trial the investigators would also like to learn more about the disease and the response to the experimental medication by measuring certain "markers".
This imaging trial will investigate the biological effects of cilengitide monotherapy on the tumor microvascular function and tumor viability in a homogenous non-pretreated subject population with newly diagnosed Gliobastoma (GBM). The purpose of this clinical trial is to study the effect that cilengitide may have on certain markers of cancer in your tumor and/or blood and to learn if there are any disease-related markers that could help in predicting how subjects respond to the administration of cilengitide.
The investigators anticipate that approximately 30 subjects will participate in this clinical trial. The clinical trial will be conducted in approximately 4 medical centers in the following countries: Germany, Poland, and Switzerland. The investigators anticipate the clinical trial will last until the end of 2013. Your participation in the trial may last up to 86 weeks.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A = Cilengitide Group | Experimental | Drug: Drug (including placebo)Cilengitide + SoC (Temolozomide + Radiotherapy) |
| Group B = Control Group | Active comparator | Other: Standard therapySoC (Temolozomide + Radiotherapy) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female subject aged ≥ 18 to ≤ 70 years at the time of informed consent signature
- Tumor tissue specimens taken from multimodal imaging-guided stereotactic biopsy must be available for histopathological confirmation of GBM and potential subsequent analysis of tissue molecular markers
- Newly diagnosed histologically proven supratentorial GBM (World Health Organization [WHO] Grade IV)
- Subject with non-resectable GBM
- Available dynamic MRI and FET-PET scan prior to randomization
Key exclusion criteria (12 listed)
- Prior chemotherapy within the last 5 years
- Prior RTX of the head (except for low-dose radiotherapy for Tinea capitis)
- Gross total resection/partial resection (GBM surgery), placement of Gliadel® wafer
- Receiving concurrent investigational agents or receipt of an investigational agent within the past 30 days prior to the first day of intensified imaging (W1D1)
- Prior systemic antiangiogenic therapy
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 |
|---|---|---|
| Drug (including placebo)Subjects will receive cilengitide monotherapy for 2 weeks (Weeks 1 and 2); thereafter, cilengitide will be given in combination with the standard treatment regimen during Weeks 3 to 36. The standard combination treatment of radiotherapy (RTX) plus Temolozomide (TMZ) will be administered for a maximum of 6 weeks (Weeks 3 to 8), followed by TMZ maintenance treatment starting 4 weeks after RTX (i.e., Week 13) for up to 6 cycles, 4 weeks per cycle. Cilengitide monotherapy treatment will be given to subjects in Group A for another 10 months as maintenance treatment (Weeks 37 to 78). Subjects in Group A may continue to receive cilengitide maintenance treatment beyond 10 months (beyond Week 78) until occurrence of progressive disease (PD) or unacceptable toxicity, or withdrawal for any other reason. A 28-day safety follow-up will be performed after the last dose of cilengitide. | Drug | Group A = Cilengitide Group |
| Standard therapyIn the first two weeks, treatment of subjects in Group B will be in line with the SoC. Thereafter the standard combination treatment of radiotherapy (RTX) plus Temolozomide (TMZ) will be administered for a maximum of 6 weeks (Weeks 3 to 8), followed by TMZ maintenance treatment starting 4 weeks after RTX (i.e., Week 13) for up to 6 cycles, 4 weeks per cycle. | Other | Group B = Control Group |
Primary outcome
Rate constant for passive contrast agent plasma/interstitium transfer (ktrans)
Time frame: 2 weeks
Any change in tumor kinetic model parameter (maximum increase in ktrans) to assess the tumor microvasculature structure and function
Fractional blood plasma volume (vp)
Time frame: 2 weeks
Any change in tumor kinetic model parameter (maximum change in vp) to assess the tumor microvasculature structure and function
Maximum tumor to brain ratio (TBRmax)
Time frame: 2 weeks
Assessment of tumor amino acid (FET) uptake (tumor viability)
6 secondary outcomes
Total tumor volume and enhancing tumor volume
Time frame: 2 weeks
Interstitial space volume fraction (putative contrast agent distribution volume) (=ve)
Time frame: 2 weeks
Apparent Diffusion coefficient (ADC)
Time frame: 2 weeks
Fractional anisotropy (FA)
Time frame: 2 weeks
Kinetic behavior of [18F]FET uptake
Time frame: 2 weeks
Mean spin-lattice relaxation time of unbound protons in water
Time frame: 2 weeks
Results and safety
The study was stopped early (reason given: Discontinuation of development program). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2014.
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.
Ute Klinkhardt, MD study director
Merck KGaA, Darmstadt, Germany
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 Standard therapy in people with Supratentorial Newly Diagnosed Inoperable Gliobastoma, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.
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 9 inclusion and 12 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: stopped early, as of the sponsor's last update on 4 Feb 2014. 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 Germany. 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 was stopped early (reason given: Discontinuation of development program). Results are not available in the source record.
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?
Rate constant for passive contrast agent plasma/interstitium transfer (ktrans) (time frame: 2 weeks). The study lists 3 primary outcomes in all. 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 4 Feb 2014.