Glioblastoma MultiformePhase 1NCT00768911
CT-322 in Combination With Radiation Therapy and Temozolomide to Treat Newly Diagnosed Glioblastoma Multiforme
A Phase 1 study testing CT-322, Temozolomide and Radiation Therapy in people with Glioblastoma Multiforme, run by Adnexus, A Bristol-Myers Squibb R&D Company at 6 sites in United States.
Trial summary
Rationale: In light of the demonstrated activity of anti-angiogenesis agents in rGBM, it is reasonable to postulate that adding these agents to standard RT and chemotherapy in the up-front management of newly diagnosed GBM may improve the clinical benefit. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- CT-322, Temozolomide and Radiation Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 6 sitesUnited States
- Study dates
- Oct 2008to Jun 2011
- 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
- Informed consent
- 18 years or older
- Newly diagnosed, histologically confirmed GBM (grade IV astrocytoma):
- Subjects will not be eligible if the original histology was a lower grade glioma and a subsequent histological diagnosis of a GBM is made
- Central independent pathology confirmation of GBM, concurrent with subject enrollment
- Subjects with sufficient biopsy material available to perform PCR analysis for MGMT promoter methylation must have tissue submitted to the designated laboratory for analysis. Subjects with insufficient tissue or indeterminate results will remain eligible for enrollment.
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- KPS ≥ 60
- Be able to begin treatment with RT/TMZ within 6 weeks after biopsy or craniotomy with satisfactory wound healing prior to initiating treatment with CT-322
- Be able to undergo serial MRIs:
- Measurable or assessable disease may or may not be present
- CT scanning may not substitute for MRI scanning
- Have adequate bone marrow, liver, renal, and metabolic function as assessed by the following:
- Hemoglobin ≥ 10.0 g/dL (unsupported)
- Absolute neutrophil count (ANC) ≥ 1,500/mm3 (unsupported)
- Platelet count ≥ 100,000/mm3 (unsupported)
- Total bilirubin ≤ 1.5 x ULN, unless due to Gilbert's disease
- ALT and AST ≤ 3 x ULN
- INR < 1.5 or PT within normal limits; and PTT within normal limits
- Serum creatinine ≤ 1.5 x ULN
- Urine protein/creatinine ratio (UPCR) < 1.0
- Serum amylase and lipase ≤ 1.5 x the ULN
- 2-dimensional echo or MUGA scan with LVEF within the institutional normal range
- Stable or decreasing dose of corticosteroids for at least 1 week prior to screening MRI
- Contraceptive measures for male and female participants for the duration of treatment and for 4 weeks following discontinuation of study treatment:
- --Female subjects having reproductive potential must have a negative serum pregnancy test within 72 hours before first administration of CT-322
- Be able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including receiving daily external beam RT in a radiation treatment facility:
- integral to or affiliated with the investigative site and in which the treating radiation therapist is a participating study investigator; and
- that has agreed to follow the radiation treatment guidance and complete the radiation treatment data collection forms
Who cannot join
- Prior CT-322 therapy or prior therapy with another VEGF-modulating agent (marketed or investigational) for malignant glioma
- History of hypersensitivity to TMZ or any of its excipients, or to Dacarbazine (DTIC)
- Prior treatment for GBM, except surgical resection and/or corticosteroid therapy
- Prior radiotherapeutic, or local (intra-tumoral) or systemic medical therapies (including but not limited to: chemotherapy, hormonal therapy, immunotherapy, anti-angiogenic therapy, implantable Gliadel® wafers, and molecularly targeted therapy) for brain tumors
- Current enrollment in another therapeutic clinical trial involving ongoing therapy
- Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study such as:
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- Pleural or pericardial effusion of ≥ grade 2
- Uncontrolled diabetes, despite optimal medical management, according to the opinion of the investigator
- Uncontrolled hypertension (defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management)
- Any active craniotomy-related wound infection
- Active clinically significant infection (> grade 2 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0 (CTCAE) requiring the use of anti-microbial agents, or that would be otherwise, in the opinion of the investigator, interfere with the ability of the subject to participate
- History of clinically significant bleeding diathesis or coagulopathy including platelet function disorder (e.g., known hemophilia or von Willebrand disease) or acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
- Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding untreated or recurring
- Untreated peptic ulcer disease or peptic ulcer disease treated for < 3 months
- Non-healing wound (including craniotomy wound), ulcer, or bone fracture; or
- Glomerulonephritis or other protein-wasting glomerulopathy
- Within 12 months before enrollment had:
- Thrombotic or embolic cerebrovascular accident or transient ischemic attacks
- CNS bleed (other than stable, grade 1)
- Intraocular bleed, or any medical condition, which in the opinion of the investigator increases the risk for intra-ocular bleeding
- Septic endocarditis (unless deemed cured and off all antibiotic therapy for at least 3 months)
- Coronary artery bypass graft, angioplasty, vascular stenting, myocardial infarction, unstable angina; or
- Symptomatic congestive heart failure (New York Heart Association ≥ class II)
- Any intraparenchymal CNS hemorrhage at the time of enrollment except for:
- Grade 1 intraparenchymal hemorrhage in the immediate post-operative period, or
- Grade 1 intraparenchymal hemorrhage that has been stable (no significant change on 2 consecutive MRI scans at least 4 weeks apart) or improved
- Subjects with a history of prior cardiotoxic chemotherapy exposure or subjects with thoracic irradiation involving cardiac tissue
- Other, non-glioma related major surgery, open biopsy, or significant traumatic injury within 4 weeks before the first dose of CT-322
- --Placement of subcutaneous in-dwelling venous access port within 2 weeks before the first dose of CT-322
- Known human immunodeficiency virus infection or known active acute or chronic viral hepatitis
- Prior malignancy within the previous 3 years, except adequately treated basal cell skin cancer or cervical carcinoma in situ; or if the other primary malignancy is not currently clinically significant or requiring active intervention
- Has any other severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that could increase the risks associated with study participation or study drug administration or could interfere with the interpretation of the study results and, in the judgment of the investigator, would make the subject inappropriate for entry in this study or non-compliant with study-related procedures
- Subjects with medical conditions that would not permit, in the judgment of the investigator, the safe discontinuation of medications that are prohibited throughout the course of the study
- Any condition requiring therapeutic anti-coagulation with either oral (e.g., warfarin type) or injectable anti-coagulants; however, low-dose (i.e., 1 mg daily [QD]) warfarin is permitted for venous port patency maintenance
- Females who are pregnant or breast feeding.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
University of Chicago Medical Center
Chicago, Illinois, 60637
Duke University Medical Center
Durham, North Carolina, 27710
University of Kentucky Hospital
Lexington, Kentucky, 40536
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Washington University Cancer Center
St Louis, Missouri, 63110
SUNY Upstate Medical University
Syracuse, New York, 13210
About this study
Official title: Phase 1, Open Label, Multi-Center Study To Evaluate The Safety And Tolerability of CT-322 Administered In Combination With Focal Brain Radiotherapy And Temozolomide To Subjects With Newly Diagnosed Glioblastoma Multiforme
Rationale:
In light of the demonstrated activity of anti-angiogenesis agents in rGBM, it is reasonable to postulate that adding these agents to standard RT and chemotherapy in the up-front management of newly diagnosed GBM may improve the clinical benefit. This study will examine the safety and tolerability of adding CT-322 to the standard radiation therapy/temozolomide (RT/TMZ) backbone of treatment for newly diagnosed GBM
- Conditions
- Glioblastoma Multiforme
- Being tested
- CT-322, Temozolomide, Radiation Therapy
- Keywords
- glioblastoma, Glioblastoma multiforme (newly diagnosed)
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CT-322Drug
Intravenous solution, intravenous administration, starting dose level of 0.5 mg/kg/week
Dose levels: 0.5 mg/kg/week, 1.0 mg/kg/week, 2.0 mg/kg/week
TemozolomideDrug
Also called Temodar
75 mg/M2/day p.o. continuously 7 days per week during concurrent RT (max: 49 days)
150 mg/M2/day X 5 days; adjuvant cycle #1
200 mg/M2/day X 5 days; subsequent adjuvant cycles (# 2-12) if tolerability criteria met
Radiation TherapyProcedure or surgery
RT will consist of fractionated focal irradiation administered using 2 Gy/fraction, QD x 5 days/week for 6 weeks, for a total dose of 60 Gy
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: CT-322; Drug: Temozolomide; Procedure: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety and tolerability of CT-322 administered in combination with standard focal brain RT/TMZ to subjects with newly diagnosed GBM
Measured: 15 ± 5 days post the last dose of study drug
Establish the recommended Phase 2 dose for the QW schedule of CT-322 for use in this combination
Measured: Every 4 weeks until MTD or 2.0 mg/kg dose level is reached
Secondary outcomes (4)
To describe the PK of TMZ and its active metabolite (MTIC) when TMZ is administered alone and when it is co-administered with CT-322 to a subset of approximately 12 subjects with newly diagnosed GBM
Measured: Cycle 1, day 1 of RT phase of treatment
To describe the peak and trough concentrations of CT-322 when administered alone and when co-administered with TMZ
Measured: RT phase treatment weeks 1-3, 5, 7-10, day 1. Post RT phase cycles 1-3, day 1; then day 1 every 3 cycles thereafter; EOS visit
To evaluate the immunogenicity of CT-322 when administered in combination with standard focal brain RT/TMZ to subjects with newly diagnosed GBM
Measured: RT phase treatment weeks 1, 5, 7-8, day 1. Post RT phase cycles 1 and 3, day 1; then day 1 every 3 cycles thereafter; EOS visit
To characterize the plasma biomarker response to CT-322 when administered in combination with standard focal brain RT/TMZ to subjects with newly diagnosed GBM
Measured: RT phase treatment weeks 1-3, 5, 7-8, day 1. Post RT phase cycles 1-3, day 1, then day 1 every 3 cycles thereafter; EOS visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionOct 2010 (estimated)
- Study completionJun 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma MultiformeStudies 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Adnexus, A Bristol-Myers Squibb R&D Company
- Sponsor type
- Industry (pharma, biotech, devices)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00768911
- Sponsor's protocol ID
- CT-322.003
- Status last verified
- Oct 2010
- First submitted
- 7 Oct 2008
- Last updated
- 27 Oct 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Open Label, Multi-Center Study To Evaluate The Safety And Tolerability of CT-322 Administered In Combination With Focal Brain Radiotherapy And Temozolomide To Subjects With Newly Diagnosed Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT00768911
- Acronym / sponsor ID
- CT-322.003
- Conditions
- Glioblastoma Multiforme
- Keywords
- glioblastoma, Glioblastoma multiforme (newly diagnosed)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Adnexus, A Bristol-Myers Squibb R&D CompanyIndustry (pharma, biotech, devices)
- Study start
- Oct 2008
- Primary completion
- Oct 2010 (estimated)
- Study completion
- Jun 2011 (estimated)
- First posted
- 8 Oct 2008 (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.
Rationale:
In light of the demonstrated activity of anti-angiogenesis agents in rGBM, it is reasonable to postulate that adding these agents to standard RT and chemotherapy in the up-front management of newly diagnosed GBM may improve the clinical benefit. This study will examine the safety and tolerability of adding CT-322 to the standard radiation therapy/temozolomide (RT/TMZ) backbone of treatment for newly diagnosed GBM
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: CT-322, Drug: Temozolomide, Procedure: Radiation Therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Informed consent
- 18 years or older
- Newly diagnosed, histologically confirmed GBM (grade IV astrocytoma):
- KPS ≥ 60
- Be able to begin treatment with RT/TMZ within 6 weeks after biopsy or craniotomy with satisfactory wound healing prior to initiating treatment with CT-322
Key exclusion criteria (35 listed)
- Prior CT-322 therapy or prior therapy with another VEGF-modulating agent (marketed or investigational) for malignant glioma
- History of hypersensitivity to TMZ or any of its excipients, or to Dacarbazine (DTIC)
- Prior treatment for GBM, except surgical resection and/or corticosteroid therapy
- Prior radiotherapeutic, or local (intra-tumoral) or systemic medical therapies (including but not limited to: chemotherapy, hormonal therapy, immunotherapy, anti-angiogenic therapy, implantable Gliadel® wafers, and molecularly targeted therapy) for brain tumors
- Current enrollment in another therapeutic clinical trial involving ongoing 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 |
|---|---|---|
| CT-322Intravenous solution, intravenous administration, starting dose level of 0.5 mg/kg/week Dose levels: 0.5 mg/kg/week, 1.0 mg/kg/week, 2.0 mg/kg/week | Drug | 1 |
| TemozolomideAlso: Temodar75 mg/M2/day p.o. continuously 7 days per week during concurrent RT (max: 49 days) 150 mg/M2/day X 5 days; adjuvant cycle #1 200 mg/M2/day X 5 days; subsequent adjuvant cycles (# 2-12) if tolerability criteria met | Drug | 1 |
| Radiation TherapyRT will consist of fractionated focal irradiation administered using 2 Gy/fraction, QD x 5 days/week for 6 weeks, for a total dose of 60 Gy | Procedure or surgery | 1 |
Primary outcome
Evaluate the safety and tolerability of CT-322 administered in combination with standard focal brain RT/TMZ to subjects with newly diagnosed GBM
Time frame: 15 ± 5 days post the last dose of study drug
Establish the recommended Phase 2 dose for the QW schedule of CT-322 for use in this combination
Time frame: Every 4 weeks until MTD or 2.0 mg/kg dose level is reached
4 secondary outcomes
To describe the PK of TMZ and its active metabolite (MTIC) when TMZ is administered alone and when it is co-administered with CT-322 to a subset of approximately 12 subjects with newly diagnosed GBM
Time frame: Cycle 1, day 1 of RT phase of treatment
To describe the peak and trough concentrations of CT-322 when administered alone and when co-administered with TMZ
Time frame: RT phase treatment weeks 1-3, 5, 7-10, day 1. Post RT phase cycles 1-3, day 1; then day 1 every 3 cycles thereafter; EOS visit
To evaluate the immunogenicity of CT-322 when administered in combination with standard focal brain RT/TMZ to subjects with newly diagnosed GBM
Time frame: RT phase treatment weeks 1, 5, 7-8, day 1. Post RT phase cycles 1 and 3, day 1; then day 1 every 3 cycles thereafter; EOS visit
To characterize the plasma biomarker response to CT-322 when administered in combination with standard focal brain RT/TMZ to subjects with newly diagnosed GBM
Time frame: RT phase treatment weeks 1-3, 5, 7-8, day 1. Post RT phase cycles 1-3, day 1, then day 1 every 3 cycles thereafter; EOS visit
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2010.
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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.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CT-322, Temozolomide and Radiation Therapy in people with Glioblastoma Multiforme, run by Adnexus, A Bristol-Myers Squibb R&D Company at 6 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 28 inclusion and 35 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: status not confirmed, as of the sponsor's last update on 27 Oct 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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 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?
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?
Evaluate the safety and tolerability of CT-322 administered in combination with standard focal brain RT/TMZ to subjects with newly diagnosed GBM (time frame: 15 ± 5 days post the last dose of study drug). The study lists 2 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 27 Oct 2010.