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A Phase I Study of CCI-779, and Temozolomide in Combination With Radiation Therapy in Glioblastoma Multiforme


Phase 1
18 Years
N/A
Not Enrolling
Both
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

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Trial Information

A Phase I Study of CCI-779, and Temozolomide in Combination With Radiation Therapy in Glioblastoma Multiforme


PRIMARY OBJECTIVES:

I. 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:

I. 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.


Inclusion Criteria:



- 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

- 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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)

Outcome Time Frame:

Up to 24 weeks

Safety Issue:

Yes

Principal Investigator

Jann Sarkaria

Investigator Role:

Principal Investigator

Investigator Affiliation:

North Central Cancer Treatment Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00642

NCT ID:

NCT00316849

Start Date:

May 2006

Completion Date:

Related Keywords:

  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Glioblastoma
  • Gliosarcoma

Name

Location

Mayo ClinicRochester, Minnesota  55905
Iowa Methodist Medical CenterDes Moines, Iowa  50309
Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Medical Oncology and Hematology AssociatesDes Moines, Iowa  50309
Altru Cancer CenterGrand Forks, North Dakota  58206
Mayo Clinic in FloridaJacksonville, Florida  32224
Medical Oncology and Hematology Associates-West Des MoinesClive, Iowa  50325
Iowa Oncology Research Association CCOPDes Moines, Iowa  50309
Mercy CapitolDes Moines, Iowa  50307
Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des MoinesDes Moines, Iowa  50309