Phase III Study of Rindopepimut/GM-CSF in Patients With Newly Diagnosed Glioblastoma - Full Text View

Sponsor:	Celldex Therapeutics
Information provided by (Responsible Party):	Celldex Therapeutics
ClinicalTrials.gov Identifier:	NCT01480479

Purpose

This 2-arm, randomized, phase III study will investigate the efficacy and safety of the addition of rindopepimut (an experimental cancer vaccine that may act to promote anti-cancer effects in patients who have tumors that express the EGFRvIII protein) to the current standard of care (temozolomide) in patients with recently diagnosed glioblastoma, a type of brain cancer.

All patients will be administered temozolomide, the standard treatment for glioblastoma. Half the patients will be randomly assigned to receive rindopepimut and half the patients will be randomly assigned to receive a control called keyhole limpet hemocyanin.

Patients will be treated in a blinded fashion (neither the patient or the doctor will know which arm of the study the patient is on). Patients will be treated until disease progression or intolerance to therapy and all patients will be followed for survival.

Condition	Intervention	Phase
Glioblastoma Small Cell Glioblastoma Giant Cell Glioblastoma Gliosarcoma Glioblastoma With Oligodendroglial Component	Drug: Rindopepimut (CDX-110) with GM-CSF Drug: Temozolomide Drug: KLH	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	An International, Randomized, Double-Blind, Controlled Study of Rindopepimut/GM-CSF With Adjuvant Temozolomide in Patients With Newly Diagnosed, Surgically Resected, EGFRvIII-positive Glioblastoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide Sargramostim

U.S. FDA Resources

Further study details as provided by Celldex Therapeutics:

Primary Outcome Measures:

Overall Survival [ Time Frame: During treatment and every three months from end of treatment through end of study or approximately up to 5 years. ] [ Designated as safety issue: No ]
The primary efficacy endpoint of Overall Survival is defined as the number of months from randomization to the date of death (whatever the cause), and will be censored for patients who remain alive at completion of the study for patients with a gross total resection (~n=374). The overall survival of patients will be monitored and compared between the two study arms until the end of the study.

Secondary Outcome Measures:

Progression-free survival [ Time Frame: Every 12 weeks from Day 1 through progression or initiation of other anti-cancer therapy ] [ Designated as safety issue: No ]
Compare progression-free survival between the two treatment arms
Safety and Tolerability [ Time Frame: Until day 28 of follow up ] [ Designated as safety issue: Yes ]
Safety and tolerability will be measured by comparing the two arms in regards to vital sign measurement, physical and neurological examination, adverse events reporting, ECOG performance status, and EORTC core Quality of Life Questionnaire

Estimated Enrollment:	440
Study Start Date:	November 2011
Estimated Primary Completion Date:	November 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Rindopepimut/GM-CSF plus Temozolomide	Drug: Rindopepimut (CDX-110) with GM-CSF Two intradermal injections two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8 mL containing approximately 500 mcg CDX-110 and 150 mcg GM CSF. Other Name: CDX-110 with sargramostim (GM-CSF) (Leukine®) Drug: Temozolomide 150 to 200 mg/m2 for 5 days during each 28-day cycle for a minimum of six cycles or a maximum of 12 cycles, or until intolerance or progression. Other Names: Temodar Temodal
Active Comparator: KLH plus Temozolomide	Drug: Temozolomide 150 to 200 mg/m2 for 5 days during each 28-day cycle for a minimum of six cycles or a maximum of 12 cycles, or until intolerance or progression. Other Names: Temodar Temodal Drug: KLH Two intradermal injections two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8mL containing approximately 100mcg of KLH.

Arms

Assigned Interventions

Experimental: Rindopepimut/GM-CSF plus Temozolomide

Drug: Rindopepimut (CDX-110) with GM-CSF

Two intradermal injections two weeks apart, followed by monthly injections until tumor progression or intolerance.

Each dose will be 0.8 mL containing approximately 500 mcg CDX-110 and 150 mcg GM CSF.

Other Name: CDX-110 with sargramostim (GM-CSF) (Leukine®)

Drug: Temozolomide

150 to 200 mg/m2 for 5 days during each 28-day cycle for a minimum of six cycles or a maximum of 12 cycles, or until intolerance or progression.

Other Names:

Temodar
Temodal

Active Comparator: KLH plus Temozolomide

Drug: Temozolomide

150 to 200 mg/m2 for 5 days during each 28-day cycle for a minimum of six cycles or a maximum of 12 cycles, or until intolerance or progression.

Other Names:

Temodar
Temodal

Drug: KLH

Two intradermal injections two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8mL containing approximately 100mcg of KLH.

Detailed Description:

The purpose of this research study is to find out whether adding an experimental vaccine called rindopepimut (also known as CDX-110) to the commonly used chemotherapy drug temozolomide can help improve the life expectancy of patients with newly diagnosed, resected EGFRvIII positive glioblastoma.

The duration of participation in this study may be up to 5 years. After you are screened and enrolled in the study, you will be administered temozolomide and either rindopepimut/GM-CSF or KLH until either disease progression or intolerance to the medications. If your tumor progresses while on this study, your doctor may treat you with other therapies that are not part of the study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Among other criteria, patients must meet the following conditions to be eligible for the study:

Adult patients, ≥ 18 years old
Newly diagnosed glioblastoma
Attempted surgical resection followed by conventional chemoradiation
Documented EGFRvIII positive tumor status by a Sponsor designated laboratory
No evidence of progressive disease from the post-operative period to the post-chemoradiation period
Candidate for, and agrees to receive, adjuvant (maintenance) temozolomide therapy
Systemic corticosteroid therapy at ≤2 mg of dexamethasone or equivalent per day for at least 3 days prior to randomization
WHO-ECOG Performance Status ≤ 2

Exclusion Criteria:

Among other criteria, patients who meet the following conditions are NOT eligible for the study:

Stereotactic biopsy only (without further surgical resection)
Presence of diffuse leptomeningeal disease or gliomatosis cerebri
History, presence, or suspicion of metastatic disease
Patients who have received any additional treatment for glioblastoma, aside from surgical resection and chemoradiation with temozolomide
Active systemic infection requiring treatment
History of any malignancy (other than glioblastoma) during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer or cured, early-stage prostate cancer in a patient with PSA level less than the upper limit of normal
Planned major surgery
Evidence of current drug or alcohol abuse
Known allergy or hypersensitivity to keyhole limpet hemocyanin (KLH), GM-CSF (sargramostim; LEUKINE®), polysorbate 80 or yeast derived products, or a history of anaphylactic reactions to shellfish proteins

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01480479

Contacts

Contact: Celldex Therapeutics

Info@celldextherapeutics.com

Show 111 Study Locations

Sponsors and Collaborators

Celldex Therapeutics

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Celldex Therapeutics
ClinicalTrials.gov Identifier:	NCT01480479 History of Changes
Other Study ID Numbers:	CDX110-04
Study First Received:	November 21, 2011
Last Updated:	May 23, 2012
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by Celldex Therapeutics:

EGFRvIII
Glioblastoma
Small cell
Giant cell
Gliosarcoma

oligodendroglial
radiotherapy
chemoradiation
Tumor
temozolomide

Additional relevant MeSH terms:

Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2012