Cilengitide Imaging Trial in Glioblastoma

NCT ID: NCT01558687

Last Updated: 2014-02-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2013-02-28

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.

Conditions

Supratentorial Newly Diagnosed Inoperable Gliobastoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Group A = Cilengitide Group

Cilengitide + SoC (Temolozomide + Radiotherapy)

Group Type: EXPERIMENTAL

Drug (including placebo)

Intervention Type: 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.

Group B = Control Group

SoC (Temolozomide + Radiotherapy)

Group Type: ACTIVE_COMPARATOR

Standard therapy

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DRUG

Standard therapy

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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ute Klinkhardt, MD

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

Merck KGaA Communication Center located in

Darmstadt, , Germany

Countries

Germany

Other Identifiers

2011-003794-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EMR062041-017

Identifier Type: -

Identifier Source: org_study_id