Back to resultsCilengitide Imaging Trial in Glioblastoma
Primary Purpose
Supratentorial Newly Diagnosed Inoperable Gliobastoma
Status
Terminated
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Drug (including placebo)
Standard therapy
Sponsored by
About this trial
This is an interventional basic science trial for Supratentorial Newly Diagnosed Inoperable Gliobastoma focused on measuring Oncology, newly diagnosed inoperable glioblastoma, temolozomide, radiotherapy, dynamic MRI, Positron emission tomography, [18]FET tracer, cilengitide, World Health Organization [WHO] Grade IV
Eligibility Criteria
Inclusion Criteria:
- 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
- ECOG Performance status of 0-2
- Stable or decreasing dose of steroids for >= 5 days prior to randomization
- Given written informed consent
Exclusion Criteria:
- 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
- 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
Sites / Locations
- Merck KGaA Communication Center located in
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Group A = Cilengitide Group
Group B = Control Group
Arm Description
Cilengitide + SoC (Temolozomide + Radiotherapy)
SoC (Temolozomide + Radiotherapy)
Outcomes
Primary Outcome Measures
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
Fractional blood plasma volume (vp)
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)
Assessment of tumor amino acid (FET) uptake (tumor viability)
Secondary Outcome Measures
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
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
Apparent Diffusion coefficient (ADC)
Change in perfusion parameter ADC during the first 2 weeks of treatment with Cilengitide monotherapy
Fractional anisotropy (FA)
Change in FA during the first 2 weeks of treatment with Cilengitide monotherapy
Kinetic behavior of [18F]FET uptake
Change in tumor amino acid (FET) uptake kinetics during the first 2 weeks of treatment with Cilengitide monotherapy
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
Full Information
NCT ID
NCT01558687
First Posted
March 16, 2012
Last Updated
February 3, 2014
Sponsor
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT01558687
Brief Title
Cilengitide Imaging Trial in Glioblastoma
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Terminated
Why Stopped
Discontinuation of development program
Study Start Date
August 2012 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
February 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Supratentorial Newly Diagnosed Inoperable Gliobastoma
Keywords
Oncology, newly diagnosed inoperable glioblastoma, temolozomide, radiotherapy, dynamic MRI, Positron emission tomography, [18]FET tracer, cilengitide, World Health Organization [WHO] Grade IV
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A = Cilengitide Group
Arm Type
Experimental
Arm Description
Cilengitide + SoC (Temolozomide + Radiotherapy)
Arm Title
Group B = Control Group
Arm Type
Active Comparator
Arm Description
SoC (Temolozomide + Radiotherapy)
Intervention Type
Drug
Intervention Name(s)
Drug (including placebo)
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Standard therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Rate constant for passive contrast agent plasma/interstitium transfer (ktrans)
Description
Any change in tumor kinetic model parameter (maximum increase in ktrans) to assess the tumor microvasculature structure and function
Time Frame
2 weeks
Title
Fractional blood plasma volume (vp)
Description
Any change in tumor kinetic model parameter (maximum change in vp) to assess the tumor microvasculature structure and function
Time Frame
2 weeks
Title
Maximum tumor to brain ratio (TBRmax)
Description
Assessment of tumor amino acid (FET) uptake (tumor viability)
Time Frame
2 weeks
Secondary Outcome Measure Information:
Title
Total tumor volume and enhancing tumor volume
Description
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
Time Frame
2 weeks
Title
Interstitial space volume fraction (putative contrast agent distribution volume) (=ve)
Description
Change in the tumor extravascular extracellular space volume during the first 2 weeks of treatment with Cilengitide monotherapy
Time Frame
2 weeks
Title
Apparent Diffusion coefficient (ADC)
Description
Change in perfusion parameter ADC during the first 2 weeks of treatment with Cilengitide monotherapy
Time Frame
2 weeks
Title
Fractional anisotropy (FA)
Description
Change in FA during the first 2 weeks of treatment with Cilengitide monotherapy
Time Frame
2 weeks
Title
Kinetic behavior of [18F]FET uptake
Description
Change in tumor amino acid (FET) uptake kinetics during the first 2 weeks of treatment with Cilengitide monotherapy
Time Frame
2 weeks
Title
Mean spin-lattice relaxation time of unbound protons in water
Description
Change in Absolute T1(mean spin-lattice relaxation time of unbound protons in water) during the first 2 weeks of treatment with Cilengitide monotherapy
Time Frame
2 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
ECOG Performance status of 0-2
Stable or decreasing dose of steroids for >= 5 days prior to randomization
Given written informed consent
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ute Klinkhardt, MD
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Merck KGaA Communication Center located in
City
Darmstadt
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
Cilengitide Imaging Trial in Glioblastoma
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