Vaccine Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme (ACTIVATe)
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Purpose
RATIONALE: Vaccines made from a peptide may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as GM-CSF, increase the number of white blood cells and platelets found in bone marrow or peripheral blood. Giving vaccine therapy after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This randomized phase II trial is studying how well vaccine therapy works in treating patients with newly diagnosed glioblastoma multiforme.
| Condition | Intervention | Phase |
|---|---|---|
|
Malignant Neoplasms of Brain |
Biological: PEP-3-KLH conjugate vaccine Biological: sargramostim Other: placebo |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Complementary Trial of an Immunotherapy Vaccine Against Tumor-Specific EGFRvIII |
- Humoral and cellular immune response [ Time Frame: 26 months ] [ Designated as safety issue: No ]
- Clinical efficacy of vaccination, in terms of progression-free survival [ Time Frame: From date of surgery/diagnosis to date of progression. ] [ Designated as safety issue: No ]
- Response to vaccination [ Time Frame: 26 months ] [ Designated as safety issue: No ]
- Toxicity [ Time Frame: 26 months ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 48 |
| Study Start Date: | September 2007 |
| Estimated Study Completion Date: | December 2016 |
| Estimated Primary Completion Date: | June 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I (part 1)
Patients receive PEP-3-KLH conjugate vaccine and sargramostim (GM-CSF) intradermally on days 1, 15, and 29 and then monthly in the absence of disease progression or unacceptable toxicity.
|
Biological: PEP-3-KLH conjugate vaccine
Given intradermally
Biological: sargramostim
Given intradermally
|
|
Active Comparator: Arm II (part 1)
Patients receive placebo vaccine intradermally on days 1, 15, and 29. Patients then receive PEP-3-KLH conjugate vaccine and GM-CSF monthly in the absence of disease progression or unacceptable toxicity.
|
Biological: PEP-3-KLH conjugate vaccine
Given intradermally
Biological: sargramostim
Given intradermally
Other: placebo
Given intradermally
|
Detailed Description:
OBJECTIVES:
Primary
- To assess humoral and cellular immune responses to adjuvant PEP-3-KLH conjugate vaccine in patients with newly diagnosed glioblastoma multiforme (GBM).
- To assess the clinical efficacy of the PEP-3-KLH conjugate vaccine, in terms of progression-free survival, in patients with newly diagnosed GBM.
Secondary
- To determine whether patients with GBM, who are known to be at least mildly immunosuppressed, can respond to standard and proven vaccine strategies.
- To assess for any potential toxicity to the PEP-3-KLH conjugate vaccine in patients with newly diagnosed GBM.
OUTLINE: This is a 2-part, multicenter study. Patients are stratified according to participating center.
Part 1: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive PEP-3-KLH conjugate vaccine and sargramostim (GM-CSF) intradermally on days 1, 15, and 29 and then monthly in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive placebo vaccine intradermally on days 1, 15, and 29. Patients then receive PEP-3-KLH conjugate vaccine and GM-CSF monthly in the absence of disease progression or unacceptable toxicity.
- Part 2: Patients receive PEP-3-KLH conjugate vaccine and GM-CSF intradermally on days 1, 15, and 29 and then monthly in the absence of disease progression or unacceptable toxicity. Alternatively, patients receive PEP-3-KLH conjugate vaccine and GM-CSF intradermally on days 1, 8, and 15, followed 1 week later by radiotherapy 5 days a week and oral temozolomide once daily for up to 7 weeks. Patients with no evidence of disease progression after completion of radiotherapy then receive PEP-3-KLH conjugate vaccine and GM-CSF intradermally monthly in the absence of disease progression or unacceptable toxicity. Beginning approximately 4 weeks after the completion of radiotherapy or after the fourth vaccination, all patients receive oral temozolomide on days 1-5 or days 1-21. Treatment with temozolomide repeats every 28 days for at least 6 months.
Patients undergo delayed-type hypersensitivity (DTH) skin testing* at baseline, after the third vaccination, and then monthly thereafter. Patients also undergo leukapheresis to obtain sufficient peripheral blood lymphocytes for immunologic monitoring at baseline, after the third vaccination, and then, if applicable, at the time of positive DTH response, disease progression, or after the sixth course of post-radiotherapy temozolomide. Methods used for immunologic monitoring include ELISPOT assays, cytotoxicity assays, fluorescence activated cell sorting (FACS), and ELISA.
NOTE: *Patients with positive DTH skin testing, also undergo skin punch biopsies.
After completion of study therapy, patients are followed periodically.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
- Histologically confirmed newly diagnosed glioblastoma multiforme
Has undergone prior gross total resection (GTR) followed by conformal radiotherapy* with or without concurrent chemotherapy
- GTR is defined as ≥ 95% volumetric resection of the contrast-enhancing component on the preoperative MRI
- Residual radiographic contrast enhancement on post-resection CT scan or MRI must be ≤ 1 cm in maximal diameter in any two perpendicular axial planes
- No evidence of disease progression after completion of radiotherapy* NOTE: *Patients may enroll in part 2 of the study within 2 weeks after surgery; these patients will receive radiotherapy with concurrent chemotherapy during the study
- EGFRvIII-positive tumor by immunohistochemistry, polymerase chain reaction, or related molecular techniques
- No diffuse leptomeningeal disease
PATIENT CHARACTERISTICS:
- Karnofsky performance status 80-100%
- Curran group status I-IV
- ANC > 1,000/mm³
- Platelet count > 50,000/mm³
- PT/PTT < 1.5 times normal
- Negative hepatitis B surface antigen (HbsAg), antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active infection requiring treatment
- No unexplained febrile illness (T_max > 101.5 F)
- No inflammatory bowel disease, lupus erythematosus, rheumatoid arthritis, or other autoimmune disease
- No known immunosuppressive disease
- No known HIV infection
- No unstable or severe concurrent medical condition, such as severe heart and lung disease or active hepatitis
- No demonstrated allergy to temozolomide or inability to tolerate temozolomide for reasons other than lymphopenia
PRIOR CONCURRENT THERAPY:
- No concurrent corticosteroids (except for nasal or inhaled steroids) at a dose above physiologic levels (> 2 mg of dexamethasone/day)
Contacts and Locations| United States, North Carolina | |
| Duke University Medical Center | |
| Durham, North Carolina, United States, 27710 | |
| United States, Texas | |
| M. D. Anderson Cancer Center at University of Texas | |
| Houston, Texas, United States, 77030-4009 | |
| Principal Investigator: | Duane Mitchell, MD, PhD | Duke University |
More Information
Additional Information:
Publications:
| Responsible Party: | John Sampson, Professor of Neurology, Duke University Medical Center |
| ClinicalTrials.gov Identifier: | NCT00643097 History of Changes |
| Obsolete Identifiers: | NCT00090597 |
| Other Study ID Numbers: | Pro00004040, P50NS020023, CDR0000589632, DUMC-5421 |
| Study First Received: | March 25, 2008 |
| Last Updated: | December 17, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Duke University:
|
adult giant cell glioblastoma adult gliosarcoma adult glioblastoma |
Additional relevant MeSH terms:
|
Brain Neoplasms Neoplasms Glioblastoma Central Nervous System Neoplasms Nervous System Neoplasms Neoplasms by Site Brain Diseases Central Nervous System Diseases Nervous System Diseases |
Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue |
ClinicalTrials.gov processed this record on May 19, 2013