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

• ClinicalTrials.gov Identifier: NCT01480479
• Recruitment Status: Completed
• Last Update Posted: January 16, 2018
• Sponsor: Celldex Therapeutics
• Information provided by (Responsible Party): Celldex Therapeutics

Tracking Information

• First Submitted Date: November 21, 2011
• First Posted Date: November 29, 2011
• Last Update Posted Date: January 16, 2018
• Study Start Date: November 2011
• Actual Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 28, 2011)

Overall Survival [ Time Frame: During treatment and every three months from end of treatment through end of study or approximately up to 5 years. ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 28, 2011)

• Progression-free survival [ Time Frame: Every 12 weeks from Day 1 through progression or initiation of other anti-cancer therapy ]
  Compare progression-free survival between the two treatment arms
• Safety and Tolerability [ Time Frame: Until day 28 of follow up ]
  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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase III Study of Rindopepimut/GM-CSF in Patients With Newly Diagnosed Glioblastoma
• 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

Brief Summary

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.

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment

Condition

• Glioblastoma
• Small Cell Glioblastoma
• Giant Cell Glioblastoma
• Gliosarcoma
• Glioblastoma With Oligodendroglial Component

Intervention

• 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
• 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.

Study Arms

• Experimental: Rindopepimut/GM-CSF plus Temozolomide
  Interventions:

  • Drug: Rindopepimut (CDX-110) with GM-CSF
  • Drug: Temozolomide
• Active Comparator: KLH plus Temozolomide
  Interventions:

  • Drug: Temozolomide
  • Drug: KLH

• Publications *: Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, Ashby L, Mechtler L, Goldlust SA, Iwamoto F, Drappatz J, O'Rourke DM, Wong M, Hamilton MG, Finocchiaro G, Perry J, Wick W, Green J, He Y, Turner CD, Yellin MJ, Keler T, Davis TA, Stupp R, Sampson JH; ACT IV trial investigators. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1373-1385. doi: 10.1016/S1470-2045(17)30517-X. Epub 2017 Aug 23.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 14, 2016): 745
• Original Estimated Enrollment (submitted: November 28, 2011): 440
• Actual Study Completion Date: November 2016
• Actual Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Brazil, Canada, Colombia, Czechia, France, Germany, Greece, Hungary, India, Israel, Italy, Mexico, Netherlands, New Zealand, Peru, Spain, Switzerland, Taiwan, Thailand, United Kingdom, United States
• Removed Location Countries: Argentina, Czech Republic, Korea, Republic of, Poland

Administrative Information

• NCT Number: NCT01480479
• Other Study ID Numbers: CDX110-04
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Celldex Therapeutics
• Study Sponsor: Celldex Therapeutics
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Celldex Therapeutics
• Verification Date: April 2017