Phase III Study of Rindopepimut/GM-CSF in Patients With Newly Diagnosed Glioblastoma (ACT IV)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Celldex Therapeutics
Sponsor:
Information provided by (Responsible Party):
Celldex Therapeutics
ClinicalTrials.gov Identifier:
NCT01480479
First received: November 21, 2011
Last updated: July 22, 2014
Last verified: July 2014
  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:


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: 700
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.

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:

  1. Adult patients, ≥ 18 years old
  2. Newly diagnosed glioblastoma
  3. Attempted surgical resection followed by conventional chemoradiation
  4. Documented EGFRvIII positive tumor status by a Sponsor designated laboratory
  5. No evidence of progressive disease from the post-operative period to the post-chemoradiation period
  6. Candidate for, and agrees to receive, adjuvant (maintenance) temozolomide therapy
  7. Systemic corticosteroid therapy at ≤2 mg of dexamethasone or equivalent per day for at least 3 days prior to randomization
  8. WHO-ECOG Performance Status ≤ 2
  9. Patients of childbearing/reproductive potential will be instructed to use birth control as defined by your doctor.

Exclusion Criteria-

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

  1. Stereotactic biopsy only (without further surgical resection)
  2. Presence of diffuse leptomeningeal disease, gliomatosis cerebri, or infratentorial disease.
  3. History, presence, or suspicion of metastatic disease
  4. Patients who have received any additional treatment for glioblastoma, aside from surgical resection and chemoradiation with temozolomide
  5. Active systemic infection requiring treatment
  6. 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, cured, early-stage prostate cancer in a patient with PSA level less than ULN,or other carcinoma in situ that has been adequately treated and cured.
  7. Planned major surgery
  8. Evidence of current drug or alcohol abuse
  9. 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
  10. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with participating in a clinical trial
  11. Women who are pregnant or lactating
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: Celldex Therapeutics Info@celldextherapeutics.com

  Show 227 Study Locations
Sponsors and Collaborators
Celldex Therapeutics
  More Information

Additional Information:
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: July 22, 2014
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
Brain Cancer
Brain Tumor
radiotherapy
chemoradiation
Tumor
temozolomide
EGFR variant III

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 August 01, 2014