Adult Giant Cell GlioblastomaPhase 1NCT00316849
Temsirolimus, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
A Phase 1 study testing pharmacological study, adjuvant therapy and 3-dimensional conformal radiation therapy in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 11 sites in United States.
Trial summary
This phase I trial is studying the side effects and best dose of temsirolimus when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma multiforme. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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?
- pharmacological study, adjuvant therapy and 3-dimensional conformal radiation therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 11 sitesUnited States
- Study dates
- May 2006to Nov 2010
- 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 glioblastoma multiforme (GBM)
- Gliosarcoma and other grade 4 astrocytoma variants (e.g., giant cell glioblastoma) allowed
- Newly diagnosed disease
- Has undergone surgical resection or biopsy of the tumor at least 1 week but no more than 6 weeks ago
- ECOG performance status 0-2
- Absolute neutrophil count ≥ 1,500/mm^3
Show all 42Show fewer
- Hemoglobin ≥ 9.0 g/dL
- Platelet count ≥ 100,000/mm^3
- Total bilirubin ≤ 2.5 times upper limit of normal (ULN)
- Cholesterol < 350 mg/dL
- Triglycerides < 400 mg/dL
- AST ≤ 2.5 times ULN
- Creatinine ≤ 1.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergy or intolerance to dacarbazine
- No ongoing or active infection
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
- No gastrointestinal tract disease affecting ability to take oral medication or requiring IV alimentation
- No significant traumatic injury within the past 21 days
- No active, uncontrolled peptic ulcer disease
- No other active cancers requiring therapy
- No concurrent combination antiretroviral therapy for HIV-positive patients
- Willing and able to comply with antibiotic prophylaxis with either trimethoprim/sulfamethoxazole (daily or 3 times per week) or monthly IV pentamidine combined with daily levofloxacin
- No prior chemotherapy for any brain tumor
- No prior temozolomide or mTOR inhibitor therapies
- No prior cranial radiotherapy
- More than 21 days since prior major surgery (excluding neurosurgical biopsy or resection of GBM)
- No prior surgical procedures affecting absorption
- No concurrent enzyme-inducing anticonvulsants, including any of the following:
- Carbamazepine
- Phenytoin
- Phenobarbital
- Primidone
- No other concurrent investigational agents
- Not receiving warfarin prior to study registration
- Concurrent warfarin allowed if patients develop an indication for it while enrolled on the protocol
Who cannot join
None listed.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Medical Oncology and Hematology Associates-West Des Moines
Clive, Iowa, 50325
Mercy Capitol
Des Moines, Iowa, 50307
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
Iowa Oncology Research Association CCOP
Des Moines, Iowa, 50309
Medical Oncology and Hematology Associates-Des Moines
Des Moines, Iowa, 50309
Medical Oncology and Hematology Associates
Des Moines, Iowa, 50314
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314
Iowa Lutheran Hospital
Des Moines, Iowa, 50316
Altru Cancer Center
Grand Forks, North Dakota, 58201
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: A Phase I Study of CCI-779, and Temozolomide in Combination With Radiation Therapy in Glioblastoma Multiforme
This phase I trial is studying the side effects and best dose of temsirolimus when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma multiforme. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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 kill tumor cells. Giving temsirolimus together with temozolomide and radiation therapy may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose of temsirolimus when administered with temozolomide in combination with radiotherapy followed by adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.
II. Assess and describe the adverse events associated with this regimen in these patients.
III. Evaluate the early response to therapy in these patients using an automated morphological MRI change detector and physiological MRI techniques, including diffusion-weighted imaging, perfusion-weighted imaging, and chemical shift imaging.
SECONDARY OBJECTIVES:
- Determine the inhibition status of mTOR signaling pathways in peripheral blood mononuclear cells in patients treated with this regimen.
II. Identify potential pharmacokinetic interactions between temozolomide and temsirolimus.
III. Correlate, preliminarily, survival, progression-free survival, and response with pre-treatment tumor tissue molecular markers in these patients.
OUTLINE: This is a multicenter, dose-escalation study of temsirolimus. Patients are assigned to 1 of 2 treatment groups.
GROUP 1: (temsirolimus with radiation and temozolomide) Patients receive temsirolimus IV over 30 minutes once weekly. Beginning 7-10 days later, patients also receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients are evaluated 4-6 weeks after completion of chemoradiotherapy. Patients with stable or responding disease proceed to adjuvant therapy. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience a dose-limiting toxicity. At least 6 patients are treated at the MTD.
GROUP 2: (radiation and temozolomide) Patients receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients are evaluated 4-6 weeks after completion of chemoradiotherapy. Patients with stable or responding disease proceed to adjuvant therapy.
ADJUVANT THERAPY: Beginning 4-6 weeks after the completion of chemoradiotherapy patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Some patients undergo blood collection for immune monitoring and translational/pharmacologic studies. After completion of study treatment, patients are followed periodically for 5 years.
- Being tested
- pharmacological study, adjuvant therapy, 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, temsirolimus
- Medical subject headings
- Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called pharmacological studies
adjuvant therapyProcedure or surgery
3-dimensional conformal radiation therapyRadiation
Also called 3D conformal radiation therapy, 3D-CRT
intensity-modulated radiation therapyRadiation
Also called IMRT
temsirolimusDrug
Also called CCI-779, cell cycle inhibitor 779, Torisel
Given IV
temozolomideDrug
Also called SCH 52365, Temodal, Temodar, TMZ
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Treatment (temsirolimus, temozolomide, radiation therapy) | Experimental | GROUP 1: (temsirolimus with radiation and temozolomide) Patients receive temsirolimus IV over 30 minutes once weekly. Beginning 7-10 days later, patients also receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. GROUP 2: (radiation and temozolomide) Patients receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. ADJUVANT THERAPY: Beginning 4-6 weeks after the completion of chemoradiotherapy patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Receives: Other: pharmacological study; Procedure: adjuvant therapy; Radiation: 3-dimensional conformal radiation therapy; Radiation: intensity-modulated radiation therapy; Drug: temsirolimus; Drug: temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximally tolerated dose (MTD), determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
Measured: Up to 24 weeks
Time to treatment related toxicity as assessed by hematologic measures and CTCAE v3.0
Measured: From registration to documentation of toxicity, up to 5 years
Time to treatment related toxicity greater than grade 3, assessed by CTCAE v3.0
Measured: From registration to documentation of toxicity, up to 5 years
Time to progression
Measured: From registration to documentation of progression, up to 5 years
Time to treatment failure
Simple summary statistics will be supplemented with Kaplan-Meier survival estimates and related confidence intervals.The effect of dose and ancillary dichotomized covariates such as gender or age (<50 years versus 50+ years) will be explored using logrank testing involving one covariate at a time.
Measured: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by patient, up to 5 years
Response to therapy associated with patient outcome, as assessed by automated morphological MRI change detector and physiological MRI techniques, including diffusion-weighted imaging, perfusion-weighted imaging, and chemical shift imaging
Logistic regression and Cox proportional hazards models will be used to determine the association between changes in tumor volume (as assessed by a software package) and tumor response and 12-month survival (logistic regression) and progression-free and overall survival (Cox proportional hazards models).
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2006 (estimated)
- Study startMay 2006
- Primary completionNov 2010
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jann Sarkaria, Principal investigator, North Central Cancer Treatment Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00316849
- Sponsor's protocol ID
- NCI-2009-00642
- Other IDs
- N027D, CDR0000467232, NCCTG-N027D, U10CA025224
- Status last verified
- Apr 2013
- First submitted
- 19 Apr 2006
- Last updated
- 10 Apr 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of CCI-779, and Temozolomide in Combination With Radiation Therapy in Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT00316849
- Acronym / sponsor ID
- NCI-2009-00642
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- May 2006
- Primary completion
- Nov 2010 (actual)
- First posted
- 21 Apr 2006 (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 phase I trial is studying the side effects and best dose of temsirolimus when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma multiforme. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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 kill tumor cells. Giving temsirolimus together with temozolomide and radiation therapy may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose of temsirolimus when administered with temozolomide in combination with radiotherapy followed by adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.
II. Assess and describe the adverse events associated with this regimen in these patients.
III. Evaluate the early response to therapy in these patients using an automated morphological MRI change detector and physiological MRI techniques, including diffusion-weighted imaging, perfusion-weighted imaging, and chemical shift imaging.
SECONDARY OBJECTIVES:
- Determine the inhibition status of mTOR signaling pathways in peripheral blood mononuclear cells in patients treated with this regimen.
II. Identify potential pharmacokinetic interactions between temozolomide and temsirolimus.
III. Correlate, preliminarily, survival, progression-free survival, and response with pre-treatment tumor tissue molecular markers in these patients.
OUTLINE: This is a multicenter, dose-escalation study of temsirolimus. Patients are assigned to 1 of 2 treatment groups.
GROUP 1: (temsirolimus with radiation and temozolomide) Patients receive temsirolimus IV over 30 minutes once weekly. Beginning 7-10 days later, patients also receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients are evaluated 4-6 weeks after completion of chemoradiotherapy. Patients with stable or responding disease proceed to adjuvant therapy. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience a dose-limiting toxicity. At least 6 patients are treated at the MTD.
GROUP 2: (radiation and temozolomide) Patients receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients are evaluated 4-6 weeks after completion of chemoradiotherapy. Patients with stable or responding disease proceed to adjuvant therapy.
ADJUVANT THERAPY: Beginning 4-6 weeks after the completion of chemoradiotherapy patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Some patients undergo blood collection for immune monitoring and translational/pharmacologic studies. After completion of study treatment, patients are followed periodically for 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (temsirolimus, temozolomide, radiation therapy) | Experimental | Other: pharmacological study, Procedure: adjuvant therapy, Radiation: 3-dimensional conformal radiation therapy, Radiation: intensity-modulated radiation therapy, Drug: temsirolimus, Drug: temozolomideGROUP 1: (temsirolimus with radiation and temozolomide) Patients receive temsirolimus IV over 30 minutes once weekly. Beginning 7-10 days later, patients also receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. GROUP 2: (radiation and temozolomide) Patients receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. ADJUVANT THERAPY: Beginning 4-6 weeks after the completion of chemoradiotherapy patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (42 listed)
- Histologically confirmed glioblastoma multiforme (GBM)
- Newly diagnosed disease
- ECOG performance status 0-2
- Absolute neutrophil count ≥ 1,500/mm^3
- Hemoglobin ≥ 9.0 g/dL
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 |
|---|---|---|
| pharmacological studyAlso: pharmacological studies | Other | Treatment (temsirolimus, temozolomide, radiation therapy) |
| adjuvant therapy | Procedure or surgery | Treatment (temsirolimus, temozolomide, radiation therapy) |
| 3-dimensional conformal radiation therapyAlso: 3D conformal radiation therapy, 3D-CRT | Radiation | Treatment (temsirolimus, temozolomide, radiation therapy) |
| intensity-modulated radiation therapyAlso: IMRT | Radiation | Treatment (temsirolimus, temozolomide, radiation therapy) |
| temsirolimusAlso: CCI-779, cell cycle inhibitor 779, ToriselGiven IV | Drug | Treatment (temsirolimus, temozolomide, radiation therapy) |
| temozolomideAlso: SCH 52365, Temodal, Temodar, TMZGiven orally | Drug | Treatment (temsirolimus, temozolomide, radiation therapy) |
Primary outcome
Maximally tolerated dose (MTD), determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
Time frame: Up to 24 weeks
Time to treatment related toxicity as assessed by hematologic measures and CTCAE v3.0
Time frame: From registration to documentation of toxicity, up to 5 years
Time to treatment related toxicity greater than grade 3, assessed by CTCAE v3.0
Time frame: From registration to documentation of toxicity, up to 5 years
Time to progression
Time frame: From registration to documentation of progression, up to 5 years
Time to treatment failure
Time frame: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by patient, up to 5 years
Simple summary statistics will be supplemented with Kaplan-Meier survival estimates and related confidence intervals.The effect of dose and ancillary dichotomized covariates such as gender or age (<50 years versus 50+ years) will be explored using logrank testing involving one covariate at a time.
Response to therapy associated with patient outcome, as assessed by automated morphological MRI change detector and physiological MRI techniques, including diffusion-weighted imaging, perfusion-weighted imaging, and chemical shift imaging
Time frame: Up to 5 years
Logistic regression and Cox proportional hazards models will be used to determine the association between changes in tumor volume (as assessed by a software package) and tumor response and 12-month survival (logistic regression) and progression-free and overall survival (Cox proportional hazards models).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2013.
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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.
Jann Sarkaria principal investigator
North Central Cancer Treatment Group
11 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 pharmacological study, adjuvant therapy and 3-dimensional conformal radiation therapy in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 11 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 42 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: finished, as of the sponsor's last update on 10 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximally tolerated dose (MTD), determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) (time frame: Up to 24 weeks). The study lists 6 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 10 Apr 2013.