Bevacizumab Alone Versus Dose-dense Temozolomide Followed by Bevacizumab for Recurrent Glioblastoma, Phase III

NCT02761070 | Unknown Phase 3 DMC

• 1 other identifier: JCOG1308C
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 37

Brief Summary

The aim of this Phase III study is to evaluate the superiority of dose-dense temozolomide (ddTMZ) followed by bevacizumab at ddTMZ failure for glioblastoma at first recurrence or progression, comparing to bevacizumab alone.

Conditions

Glioblastoma; Recurrence; Progression

Keywords

glioblastoma; recurrent; dose-dense temozolomide; bevacizumab

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Overall survival will be measured from registration until death for any reason. If the patient is alive at last follow-up, the patient will be censored at the last time of confirmation of survival.

  Time to event. Up to 2 years from the last patient in.

Secondary Outcomes (11)

• Progression-free survival (PFS)

  Time to event. Up to 2 years from the last patient in.

• 6-month progression-free survival (6m-PFS)

  6 months from registration

• Complete response rate

  Through study completion, an average of 1 year

• Response rate

  Through study completion, an average of 1 year

• Adverse events

  Up to 1 year after completion/termination of the protocol treatment.

Study Arms (2)

Bevacizumab (BEV) alone

ACTIVE COMPARATOR

Bevacizumab 10 mg/kg, day 1 div, every 2 weeks

Drug: Bevacizumab

Dose Dense Temozolomide Followed by BEV

EXPERIMENTAL

Temozolomide (120 mg/m2, po, 7 days on/7 days off, every 2 weeks per cycle) up to 48 cycles. The dose will be escalated to 150 mg/m2 at 3rd cycle if the defined conditions are met throughout the first 2 cycles. At recurrence or progression, bevacizumab alone(10 mg/kg, day 1 div, every 2 weeks)

Drug: Temozolomide; Drug: Bevacizumab

Interventions

Temozolomide DRUG

Also known as: Temodar, Temodal

Dose Dense Temozolomide Followed by BEV

Bevacizumab DRUG

Also known as: Avastin

Bevacizumab (BEV) alone; Dose Dense Temozolomide Followed by BEV

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven diagnosis of glioblastoma (including giant cell glioblastoma and gliosarcoma) by WHO2007 criteria.
• For patients who did not undergo surgery for recurrent disease; pre-registration contrast MRI should confirm; (i)progressive or recurrent glioblastoma; (ii)no evidence of acute or subacute cerebral hemorrhage at enrolment; (iii)presence of a measurable lesion.
• For patients who underwent surgery for recurrent disease; (i)progressive or recurrent glioblastoma must be confirmed on contrast MRI before reoperation; (ii)glioblastoma or anaplastic astrocytoma must be histologically identified in the tissue resected at reoperation; (iii)presence of measurable lesions is not mandatory on pre-registration contrast MRI (more than 4 days after reoperation); (iv)no MRI evidence of aggravating cerebral hemorrhage.
• No evidence of tumors in the cerebellum, brain stem, optic nerve, olfactory nerve, and pituitary gland.
• No evidence of meningeal dissemination or gliomatosis cerebri.
• Prior treatment for newly-diagnosed glioblastoma (or diffuse astrocytoma (Grade II) or anaplastic astrocytoma (Grade III)) with postoperative TMZ administered concomitantly with radiotherapy (\>=54 Gy for \<=69 years old; \>=30 Gy for \>=70 years old) and at least for two cycles (5/28d) as an adjuvant treatment have been given.
• No history of prior treatment with stereotactic radiotherapy (ex. Gamma-knife/Cyberknife), proton beam irradiation, neutron capture therapy, and chemotherapies except standard dose TMZ and immunotherapy (vaccines, immune checkpoint inhibitors, antibodies etc.), bevacizumab (12 weeks or more after termination of prior upfront bevacizumab use) that were combined with TMZ, and intraoperative placement of carmustine wafers, for glioblastoma (including diffuse astrocytoma (Grade II) and anaplastic astrocytoma (Grade III) at onset) diagnosed with WHO2007 criteria.
• Time periods required from the last day of the prior treatment indicated at registration.
• ①Peptide vaccination, immune checkpoint inhibitors, antibodies: 4 weeks.
• ②Bevacizumab: 12 weeks.
• More than 90 days after completion of radiotherapy. For those who underwent reoperation, between 21 and 28 days postoperatively.
• Age between 20 and 75 years at enrolment.
• Karnofsky Performance Status \>= 60 within 14 days before enrolment.
• No prior treatment with chemotherapy, molecular targeted therapy, or radiotherapy to head and neck area for other malignancies.
• Adequate organ function.

You may not qualify if:

• Synchronous or metachronous (within 5 years) malignancy, except for carcinoma in situ or mucosal tumors curatively treated with local therapy
• Active infection requiring systemic therapy
• Body temperature \>= 38 degrees Celsius at registration
• Women during pregnancy, possible pregnancy, within 28 days after delivery, or breast-feeding
• Psychosis or with psychotic symptom
• Continuous systemic use of immunosuppressant except for steroid
• Uncontrolled diabetes mellitus
• Unstable angina within 3 weeks, with a history of myocardial infarction within 6 months, or New York Heart Association (NYHA) class II or greater congestive heart failure
• Inadequately controlled hypertension (cannot be controlled to a systolic pressure of \>= 150 mmHg and a diastolic pressure of \>= 100 mmHg)
• History of symptomatic cerebrovascular disorder (including subarachnoid hemorrhage, cerebral infarction and transient ischemic attack) within 6 months or history of vascular disorder requiring intervention (including venous/arterial thrombosis or embolism and aortic aneurysm) within 6 moths
• History of grade \>= 2 hemoptysis within 28 days
• History of hemorrhagic tendency (e.g., coagulation disorder) or any grade \>= 3 hemorrhage within 28 days
• History of gastrointestinal perforation, fistula, abdominal abscess or uncontrolled peptic ulcer within 6 months
• Interstitial pneumonia, pulmonary fibrosis, or severe lung emphysema
• Severe non-healing wound or traumatic fracture at enrolment

Sponsors & Collaborators

• Kyorin University: lead
• Japan Clinical Oncology Group: collaborator

Study Sites (37)

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

Location

Fujita Health University Hospital

Toyoake, Aichi-ken, 470-1192, Japan

Location

Hirosaki University School of Medicine

Hirosaki, Aomori, 036-8563, Japan

Location

Ehime University Graduate School of Medicine

Shizukawa, Ehime, 791-0295, Japan

Location

Kurume University Hospital

Kurume-shi, Fukuoka, 830-0011, Japan

Location

Sapporo Medical University Hospital

Sapporo, Hokkaido, 060-8543, Japan

Location

Kobe University Hospital

Kobe, Hyōgo, 650-0017, Japan

Location

University of Tsukuba Hospital

Tsukuba, Ibaraki, 305-8576, Japan

Location

Iwate Medical University

Morioka, Iwate, 020-8505, Japan

Location

Tohoku University Graduate School of Medicine

Sendai, Miyagi, 980-8574, Japan

Location

Nagasaki University Hospital

Nagasaki, Nagasaki, 852-8501, Japan

Location

Kansai Medical University

Hirakata, Osaka, 573-1191, Japan

Location

Osaka University Graduate School of Medicine

Suita, Osaka, 565-0871, Japan

Location

Saga University Hospital

Saga, Saga-ken, 849-8501, Japan

Location

Saitama Medical University International Medical Center

Hidaka, Saitama, 350-1298, Japan

Location

Dokkyo Medical University

Shimotsuge, Tochigi, 321-0293, Japan

Location

Tokyo Medical And Dental University, Medical Hospital

Bunkyō-Ku, Tokyo, 113-8519, Japan

Location

University of Yamanashi

Chuo-shi, Yamanashi, 400-8510, Japan

Location

Chiba University Hospital

Chiba, 260-8677, Japan

Location

Kusyu University Graduate School of Medical Sciences

Fukuoka, 812-8582, Japan

Location

Hiroshima University Hospital

Hiroshima, 734-8551, Japan

Location

Kagoshima University Graduate School of Medical and Dental Sciences

Kagoshima, 890-8520, Japan

Location

Kitasato University School of Medicine

Kanagawa, 252-0374, Japan

Location

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

Location

Kyoto University Graduate School of Medicine

Kyoto, 606-8507, Japan

Location

Niigata University Medical & Dental Hospital

Niigata, 951-8520, Japan

Location

Okayama University Hospital

Okayama, 700-8558, Japan

Location

Osaka International Cancer Institute

Osaka, 541-8567, Japan

Location

Nakamura Memorial Hospital

Sapporo, 060-8570, Japan

Location

Hokkaido University Graduate School of Medicine

Sapporo, 060-8648, Japan

Location

Shizuoka Canser Center Hospital

Shizuoka, 411-8777, Japan

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

The University of Tokyo Hospital

Tokyo, 113-8655, Japan

Location

Keio University Hospital

Tokyo, 160-8582, Japan

Location

Nihon University School of Medicine Itabashi Hospital

Tokyo, 173-0032, Japan

Location

Kyorin University Faculty of Medicine, Department of Neurosurgery

Tokyo, 181-8611, Japan

Location

Yamagata University Hospital

Yamagata, 990-9585, Japan

Location

MeSH Terms

Conditions

Glioblastoma; Recurrence; Disease Progression

Interventions

Temozolomide; Bevacizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Motoo Nagane, M.D., Ph.D.

  Kyorin University Faculty of Medicine, Department of Neurosurgery

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 28, 2016
• First Posted: May 4, 2016
• Study Start: July 11, 2016
• Primary Completion: November 10, 2025
• Study Completion: November 10, 2025
• Last Updated: March 8, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

JP (37)