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Adult Giant Cell GlioblastomaPhase 1/2NCT00085254

Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

A Phase 1/2 study testing cilengitide, temozolomide and radiation therapy in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Cilengitide may stop the growth of cancer by stopping blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to damage tumor cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
cilengitide, temozolomide and radiation therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
112 participants
Where
8 sitesUnited States
Study dates
Apr 2005to Nov 2012
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme)
  • Patients must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed
  • Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
  • Absolute neutrophil count >= 1500/mm^3
  • Platelets >= 100,000/mm^3
  • Creatinine =< 1.5 mg/dl or creatinine clearance >= 60 mL/min
Show all 13Show fewer
  • Total bilirubin =< 1.5 mg/dl
  • Transaminases =< 4 times above the upper limits of the institutional normal
  • Patients must be able to provide written informed consent
  • Patients must have recovered from the immediate post-operative period and be maintained on a stable corticosteroid regimen (no increase for 5 days) prior to the start of treatment
  • Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception; women of childbearing potential must have a negative pregnancy test
  • Patients must have a Mini Mental State Exam score of >= 15
  • Patients must have tumor tissue form completed and signed by a pathologist

Who cannot join

  • Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety
  • Patients who are pregnant or breast-feeding
  • Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents)
  • Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin; patients who have been free of disease (any prior malignancy) for >= five years are eligible for this study
  • Patients who are unable to undergo an MRI evaluation
  • Patients with a history of wound-healing disorders, advanced coronary disease, or with a recent history (# 1 year) of peptic ulcer disease are ineligible

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites
  • Emory University

    Atlanta, Georgia, 30322

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: A Safety Run-in/Randomized Phase II Trial of EMD 121974 in Conjunction With Concomitant and Adjuvant Temozolomide With Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme

Cilengitide may stop the growth of cancer by stopping blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving cilengitide together with temozolomide and radiation therapy may kill more tumor cells. This randomized phase I/II trial is studying the side effects and best dose of cilengitide when given together with temozolomide and radiation therapy and to compare how well they work in treating patients with newly diagnosed glioblastoma multiforme

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety profile of EMD 121974 (cilengitide) when administered as a one-hour infusion twice a week concurrently with concomitant and adjuvant temozolomide with radiation therapy for newly diagnosed glioblastoma multiforme. (Safety Run-In)

II. To estimate overall survival in newly diagnosed patients with glioblastoma multiforme treated with EMD 121974 concurrently with concomitant and adjuvant temozolomide with radiation therapy. (Phase II)

SECONDARY OBJECTIVES:

  1. To estimate and compare overall survival between a low dose treatment group and a high dose treatment group in newly diagnosed patients with glioblastoma multiforme treated with EMD 121974 concurrently with concomitant and adjuvant temozolomide with radiation therapy. (Phase II)

II. To determine the toxicity of EMD 121974 (cilengitide) when it is administered in conjunction with concomitant and adjuvant temozolomide with radiation therapy in patients with newly diagnosed glioblastoma multiforme. (Phase II)

III. To evaluate the molecular profile of individual patients and correlate molecular expression profiles with clinical outcomes. (Phase II)

IV. To characterize tumor blood volume, tumor blood flow, and permeability ratios using perfusion MR in newly diagnosed glioblastoma multiforme and follow these parameters during treatment with EMD 121974 (cilengitide). (Phase II)

OUTLINE: This is an open-label, multicenter, safety run-in study of cilengitide followed by a randomized phase II study.

Safety Run-In:

INITIATION COURSE: Patients receive cilengitide IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.

MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of cilengitide (3 Pre-defined study dose levels are defined as: 500, 1000 and 2000mg). The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity. If no MTD (maximum tolerable dose) is defined through three steps of the dose escalation process, we will pursue the phase II safety/efficacy study with randomized treatment allocation. Patients will be randomized into one of two pre-specified treatment dosage arms, 500mg group or 2000mg group.

PHASE II:

Patients are stratified according to age (50 and under vs over 50), Karnofsky performance score (60%-80% vs 90%-100%), and tumor status (measurable vs nonmeasurable). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive radiotherapy and temozolomide as in safety run-in initiation course and cilengitide at the lower dose as in safety run-in initiation and maintenance courses.

ARM II: Patients receive radiotherapy and temozolomide as in safety run-in initiation course and cilengitide at the higher dose as in safety run-in initiation and maintenance courses.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 9-112 patients (9-18 for safety run-in and 94 [47 per treatment arm] for phase II) will be accrued for this study within 1.5-37 months

Being tested
cilengitide, temozolomide, radiation therapy, laboratory biomarker analysis, pharmacological study
Medical subject headings
Glioblastoma, Gliosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cilengitideDrug

    Also called EMD 121974

    Given IV

  • temozolomideDrug

    Also called SCH 52365, Temodal, Temodar, TMZ

    Given orally

  • radiation therapyRadiation

    Also called irradiation, radiotherapy, therapy, radiation

    Undergo radiotherapy

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00085254
Study groupRoleWhat they receive
Arm 1 (Safety Run In)ExperimentalINITIATION COURSE: Patients receive cilengitide IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6. MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Doses of cilengitide: 500mg, 1000mg and 2000mg Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
Receives: Drug: cilengitide; Drug: temozolomide; Radiation: radiation therapy; Other: laboratory biomarker analysis; Other: pharmacological study
Phase II (Arm1-500mg)ExperimentalINITIATION COURSE: Patients receive cilengitide (500mg) IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6. MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV (500mg) on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cilengitide, Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
Receives: Drug: cilengitide; Drug: temozolomide; Radiation: radiation therapy; Other: laboratory biomarker analysis; Other: pharmacological study
Phase II (Arm 2 -2000mg)ExperimentalINITIATION COURSE: Patients receive cilengitide (2000mg) IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6. MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV (2000mg) on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cilengitide,Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
Receives: Drug: cilengitide; Drug: temozolomide; Radiation: radiation therapy; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicities of EMD + RT and TMZ

    pts will be evaluated from first dose through end of initiation cycle. (6 weeks of RT+TMZ +EMD and 4 weeks of EMD alone) to review dose limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)

    DLT defined as: Known TMZ hematological toxicities will not be considered dose limiting.

    Nonhematological toxicities Grades 3-4 severity (except nausea and vomiting without sufficient antiemetic prophylaxis)

    Measured: 10 weeks

  2. Maximum Tolerated or Tolerable Dose (MTD) - 3 Pre-defined Doses

    pts will be evaluated from first dose through end of initiation cycle. (6 weeks of RT+TMZ +EMD and 4 weeks of EMD alone) to review any dose limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (safety run-in)

    DLT defined as: Known TMZ hematological toxicities will not be considered dose limiting.

    cohorts at these 3 defined doses: 500mg, 1000mg and 2000mg MTD defined as: dose producing DLT in 2 out of 6 patients or dose level below the dose which produced DLT in >/= 2 out of 3 patients, or in >/= 3 out of 6 patients If no MTD (maximum tolerable dose) was defined through 3 steps of dose escalation, phase 2 will proceed with a randomized treatment allocation of the two pre-specified dosage arms: low dose; 500mg and high dose; 2000mg

    Measured: 10 weeks

  3. Overall Survival (Phase II)

    The overall survival is calculated from time of histological diagnosis to death occurance - median based on all 112 patients, all dose levels

    Measured: up to 36 months

Secondary outcomes (2)
  1. Overall Survival Based on Dose Level - Phase 2

    survival calculated from date of initial histologic diagnosis and occurence of death. Pts at 500mg dose compared against Pts treated at 2000mg dose. Calculated using median

    Measured: Up to 3 years

  2. Frequency of Hematologic and Nonhematologic Adverse Events

    The proportion of patients with grade 3 and grade 4 hematologic and non hematologic adverse events per CTCAE 4.0

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jun 2004 (estimated)
  2. Study startApr 2005
  3. Primary completionNov 2012
  4. Study completionNov 2012

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
112 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00085254
Sponsor's protocol ID
NCI-2012-02932
Other IDs
NABTT 0306, CDR0000368451, U01CA062475
Status last verified
Oct 2015
First submitted
10 Jun 2004
Last updated
25 Feb 2016
Data monitoring committee
Yes

Publications

  • Nabors LB, Mikkelsen T, Hegi ME, Ye X, Batchelor T, Lesser G, Peereboom D, Rosenfeld MR, Olsen J, Brem S, Fisher JD, Grossman SA; New Approaches to Brain Tumor Therapy (NABTT) Central Nervous System Consortium. A safety run-in and randomized phase 2 study of cilengitide combined with chemoradiation for newly diagnosed glioblastoma (NABTT 0306). Cancer. 2012 Nov 15;118(22):5601-7. doi: 10.1002/cncr.27585. Epub 2012 Apr 19.

    PubMed 22517399

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing cilengitide, temozolomide and radiation therapy in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 8 sites in United States.

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 13 inclusion and 6 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 25 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Dose Limiting Toxicities of EMD + RT and TMZ (time frame: 10 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?

On the ClinicalTrials.gov record for NCT00085254, 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 25 Feb 2016.

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