Adult Giant Cell GlioblastomaPhase 1NCT01122888
Cilengitide and Sunitinib Malate in Treating Patients With Advanced Solid Tumors or Glioblastoma Multiforme
A Phase 1 study testing Cilengitide, Clinical Observation and Laboratory Biomarker Analysis in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This clinical trial is studying how well giving cilengitide together with sunitinib malate works in treating patients with advanced solid tumors or glioblastoma multiforme. Cilengitide and sunitinib malate may stop the growth of tumor cells by blocking blood flow to the tumor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
- What is being tested?
- Cilengitide, Clinical Observation and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2009to Apr 2015
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed solid tumor or malignant glioblastoma multiforme meeting >= 1 of the following criteria:
- Disease refractory to standard therapy
- No standard therapy exists
- Sunitinib malate monotherapy would be appropriate management
- Measurable disease is not required
- Previously treated brain metastases or primary brain neoplasms allowed provided patient is not receiving concurrent corticosteroids
Show all 71Show fewer
- Karnofsky performance status 70-100%
- Absolute neutrophil count (ANC) >= 1,500/μL
- White blood cell count (WBC) >= 3,000/μL
- Platelet count >= 100,000/μL
- Hemoglobin >= 9 g/dL
- Total bilirubin normal (unless due to documented Gilbert syndrome)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal (ULN) (< 5 times ULN in the presence of liver metastases)
- Creatinine normal OR creatinine clearance >= 60 mL/min
- Serum calcium =< 12.0 mg/dL
- QTc < 500 msec
- Patients with any of the following are allowed provided they have New York Heart Association (NYHA) class I-II cardiac function and undergo a baseline echocardiogram (ECHO)/multiple gated acquisition (MUGA):
- History of class II heart failure and asymptomatic on treatment
- Prior anthracycline exposure
- Previously treated with central thoracic radiotherapy that included the heart in the radiotherapy port
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate
- No concurrent uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness and/or social situation that would limit compliance with study requirements
- No pre-existing thyroid abnormality for which thyroid function cannot be maintained in the normal range with medication
- No documented thrombosis (pulmonary embolism or deep vein thrombosis) within the past 6 months
- No known coagulopathy or thrombophilia
- No proven gastric or duodenal ulcer or clinically significant gastrointestinal (GI) blood loss within the past 6 weeks
- No history of central nervous system (CNS) hemorrhage
- No life-threatening bleeding diathesis within the past 6 months
- No history of serious ventricular arrhythmia (i.e., ventricular fibrillation or ventricular tachycardia >= 3 beats in a row) or other significant electrocardiogram (ECG) abnormalities
- No poorly controlled hypertension (i.e., systolic blood pressure (BP) >= 150 mm Hg or diastolic BP >= 100 mm Hg)
- No condition that would impair the ability to swallow and retain sunitinib malate tablets, including any of the following:
- GI tract disease resulting in an inability to take oral medications or a requirement for IV alimentation
- Prior surgical procedures affecting absorption
- Active peptic ulcer disease
- No gastrostomy, jejunostomy, or other forms of enteral tube feeding modalities
- None of the following conditions:
- Serious or non-healing wound or ulcer
- Abdominal fistula, GI perforation, or intra-abdominal abscess within the past 28 days
- Cerebrovascular accident or transient ischemic attack within the past 12 months
- Myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within the past 12 months
- NYHA class III or IV heart failure
- Radiographically or physiologically diagnosed usual interstitial pneumonitis (UIP) or non-specific interstitial pneumonitis (NSIP)
- No bone fracture within the past 12 months
- No other concurrent anticancer agents or therapies
- More than 4 weeks since prior radiotherapy or systemic antineoplastic therapy (6 weeks for nitrosoureas, mitomycin C, or bevacizumab) and recovered
- More than 2 weeks since prior hormone replacement therapy or hormonal contraceptives
- More than 1 month since prior surgery
- At least 7 days since prior and no concurrent CYP3A4 inhibitors
- At least 12 days since prior and no concurrent CYP3A4 inducers
- Prior luteinizing hormone-releasing hormone agonists for hormone-refractory prostate cancer allowed
- Prior antiangiogenic agents (e.g., sorafenib, pazopanib, AZD2171 [cediranib maleate], PTK787 [vatalanib], or VEGF Trap [ziv-aflibercept]) allowed provided there is no disease progression
- No prior cilengitide or sunitinib malate
- No prior bevacizumab
- No other concurrent investigational agents
- No concurrent combination antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients
- No concurrent agents with proarrhythmic potential (e.g., terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, or flecainide)
- No concurrent palliative radiotherapy
- No other concurrent chemotherapy or biologic agents
- No concurrent medications that may cause QTc prolongation
- No concurrent therapeutic doses of coumarin-derivative anticoagulants (e.g., warfarin)
- Up to 2 mg of daily warfarin for the prophylaxis of thrombosis allowed
- Low-molecular weight heparin allowed provided prothrombin time (PT)/international normalized ratio (INR) =< 1.5
- No concurrent grapefruit juice
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
About this study
Official title: Pilot Biomarker Study of the Integrin AlphavBeta3 Antagonist Cilengitide (EMD121974) in Combination With Sunitinib
This clinical trial is studying how well giving cilengitide together with sunitinib malate works in treating patients with advanced solid tumors or glioblastoma multiforme. Cilengitide and sunitinib malate may stop the growth of tumor cells by blocking blood flow to the tumor. Giving cilengitide together with sunitinib malate may kill more tumor cells. Studying samples of blood in the laboratory from patients receiving cilengitide and sunitinib malate may help doctors understand the effect of these drugs on biomarkers.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the effect of cilengitide on changes in serum VEGFR2, a pharmacodynamic biomarker of sunitinib malate effects on endothelial function, during the withdrawal phase of a course of sunitinib malate in patients with advanced solid tumors or glioblastoma multiforme.
SECONDARY OBJECTIVES:
- Determine the effect of cilengitide exposure on changes in VEGFR2 over the 14-day interval from the end of sunitinib malate administration to the end of course 1 in these patients.
II. Test the safety and efficacy of this regimen in these patients. III. Develop serum collagen c-telopeptide crosslinks (CTx) as a pharmacodynamic marker for cilengitide.
OUTLINE:
COURSE I: Patients receive oral sunitinib malate on days 1-14 (weeks 1-2). Patients are then randomized to 1 of 2 treatment arms.
ARM I: Patients receive cilengitide IV over 1 hour twice in weeks 3 and 4.
ARM II: Patients do not receive treatment in weeks 3 and 4.
COURSE II: Patients in both arms then receive oral sunitinib malate on days 1-14 and cilengitide IV over 1 hour twice in weeks 3 and 4. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up periodically.
- Conditions
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Adult Solid Neoplasm, Recurrent Adult Brain Neoplasm
- Being tested
- Cilengitide, Clinical Observation, Laboratory Biomarker Analysis
- Medical subject headings
- Glioblastoma, Gliosarcoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CilengitideDrug
Also called EMD 121974, EMD-121974
Given IV
Clinical ObservationOther
Patients undergo a 2-week rest period
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (course 1) | Experimental | Patients receive cilengitide IV over 1 hour twice weekly for 2 weeks. Receives: Drug: Cilengitide; Other: Laboratory Biomarker Analysis |
| Arm II (course 1) | Other | Patients do not receive treatment and undergo a 2-week rest period. Receives: Other: Clinical Observation; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in serum VEGFR2
Measured: Over 14 days from the end of sunitinib to the end of course 1
Secondary outcomes (5)
Comparison of the change in serum VEGFR2 in courses 1 and 2
Compared using a paired t-test.
Measured: Over 14 days
Progression-free survival
Estimated using the Kaplan-Meier method. Summarized by type, grade, and attribution and compared using chi-squared tests or Fisher exact tests, as appropriate.
Measured: Assessed up to 30 days after completion of study treatment
Response rate evaluated using RECIST criteria
Summarized by type, grade, and attribution and compared using chi-squared tests or Fisher exact tests, as appropriate.
Measured: Up to 30 days after completion of study treatment
Serum type I collagen c-telopeptide crosslink measurements
Measured: Up to 30 days after completion of study treatment
Toxicity rates, graded using the NCI CTCAE version 4.0
Compared using chi-squared tests or Fisher exact tests, as appropriate.
Measured: Up to 30 days after completion of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2010 (estimated)
- Study startDec 2009
- Primary completionSep 2012
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Giant Cell GlioblastomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Michael Maitland, Principal investigator, University of Chicago Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01122888
- Sponsor's protocol ID
- NCI-2011-01455
- Other IDs
- NCI-2011-01455, CDR0000659080, UCCRC-09-259-A, 09-259-A, 8313, P30CA014599, U01CA069852
- Status last verified
- Apr 2015
- First submitted
- 12 Jan 2010
- Last updated
- 28 Apr 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Biomarker Study of the Integrin AlphavBeta3 Antagonist Cilengitide (EMD121974) in Combination With Sunitinib
- ClinicalTrials.gov ID
- NCT01122888
- Acronym / sponsor ID
- NCI-2011-01455
- Conditions
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Adult Solid Neoplasm, Recurrent Adult Brain Neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 41 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 2009
- Primary completion
- Sep 2012 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 13 May 2010 (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.
This clinical trial is studying how well giving cilengitide together with sunitinib malate works in treating patients with advanced solid tumors or glioblastoma multiforme. Cilengitide and sunitinib malate may stop the growth of tumor cells by blocking blood flow to the tumor. Giving cilengitide together with sunitinib malate may kill more tumor cells. Studying samples of blood in the laboratory from patients receiving cilengitide and sunitinib malate may help doctors understand the effect of these drugs on biomarkers.
Detailed description
PRIMARY OBJECTIVES:
- Determine the effect of cilengitide on changes in serum VEGFR2, a pharmacodynamic biomarker of sunitinib malate effects on endothelial function, during the withdrawal phase of a course of sunitinib malate in patients with advanced solid tumors or glioblastoma multiforme.
SECONDARY OBJECTIVES:
- Determine the effect of cilengitide exposure on changes in VEGFR2 over the 14-day interval from the end of sunitinib malate administration to the end of course 1 in these patients.
II. Test the safety and efficacy of this regimen in these patients. III. Develop serum collagen c-telopeptide crosslinks (CTx) as a pharmacodynamic marker for cilengitide.
OUTLINE:
COURSE I: Patients receive oral sunitinib malate on days 1-14 (weeks 1-2). Patients are then randomized to 1 of 2 treatment arms.
ARM I: Patients receive cilengitide IV over 1 hour twice in weeks 3 and 4.
ARM II: Patients do not receive treatment in weeks 3 and 4.
COURSE II: Patients in both arms then receive oral sunitinib malate on days 1-14 and cilengitide IV over 1 hour twice in weeks 3 and 4. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (course 1) | Experimental | Drug: Cilengitide, Other: Laboratory Biomarker AnalysisPatients receive cilengitide IV over 1 hour twice weekly for 2 weeks. |
| Arm II (course 1) | Other | Other: Clinical Observation, Other: Laboratory Biomarker AnalysisPatients do not receive treatment and undergo a 2-week rest period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (71 listed)
- Histologically confirmed solid tumor or malignant glioblastoma multiforme meeting >= 1 of the following criteria:
- Measurable disease is not required
- Previously treated brain metastases or primary brain neoplasms allowed provided patient is not receiving concurrent corticosteroids
- Karnofsky performance status 70-100%
- Absolute neutrophil count (ANC) >= 1,500/μL
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| CilengitideAlso: EMD 121974, EMD-121974Given IV | Drug | Arm I (course 1) |
| Clinical ObservationPatients undergo a 2-week rest period | Other | Arm II (course 1) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (course 1), Arm II (course 1) |
Primary outcome
Change in serum VEGFR2
Time frame: Over 14 days from the end of sunitinib to the end of course 1
5 secondary outcomes
Comparison of the change in serum VEGFR2 in courses 1 and 2
Time frame: Over 14 days
Progression-free survival
Time frame: Assessed up to 30 days after completion of study treatment
Response rate evaluated using RECIST criteria
Time frame: Up to 30 days after completion of study treatment
Serum type I collagen c-telopeptide crosslink measurements
Time frame: Up to 30 days after completion of study treatment
Toxicity rates, graded using the NCI CTCAE version 4.0
Time frame: Up to 30 days after completion of study treatment
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2015.
Related trials for Adult Giant Cell Glioblastoma
Active, not recruitingPhase 1
Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas
Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma
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.
Michael Maitland principal investigator
University of Chicago Comprehensive Cancer Center
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 Cilengitide, Clinical Observation and Laboratory Biomarker Analysis in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 1 site 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 71 inclusion and 0 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 28 Apr 2015. 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 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 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. 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?
Change in serum VEGFR2 (time frame: Over 14 days from the end of sunitinib to the end of course 1). 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 28 Apr 2015.