Nimotuzumab Plus Radiotherapy With Concomitant and Adjuvant Temozolomide for Cerebral Glioblastoma

Study Overview
=================
Brief Summary
-----------------
This study aimed to investigate the clinical benefit contribution and safety of nimotuzumab to the standard combined treatment for patients with newly diagnosed glioblastoma.

Official Title
-----------------
Efficacy and Safety of Nimotuzumab in Addition to Radiotherapy and Temozolomide for Cerebral Glioblastoma

Conditions
-----------------
Glioblastoma

Intervention / Treatment
-----------------
* Biological: Nimotuzumab
* Drug: Temozolomide
* Radiation: Radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Newly diagnosed, histologically proven single supratentorial GBM (WHO grade 4); EGFR positive; >50％ of the gross tumor volume removed by surgery； Karnofsky performance score (KPS) ≥ 60; Adequate renal function (creatinine ≤1.5×upper limit of normal [ULN] or creatinine clearance ≥ 60 mL/min), hepatic function (total bilirubin ≤1.5×ULN and serum transaminases ≤3×ULN), and hematologic function (white blood cell count ≥ 3,000/uL or absolute neutrophil count ≥ 1,500/uL, platelets ≥ 100,000/uL, and hemoglobin ≥ 10 g/dL). Tumor tissue was required for central pathology review and re-checking EGFR and MGMT expression status; An interval of 2 to 6 weeks between surgery and RT was required. Exclusion Criteria: Negative EGFR expression; Prior chemotherapy, anti-EGFR therapy, RT, or a history of malignancy in the previous 5 years; Patients with severe complications or active infection; Continuous vomiting that could interfere with the oral administration of TMZ; Pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nimotuzumab plus RT and temozolomide.<br>Nimotuzumab, administered once a week intravenously in addition to radiotherapy with concomitant and adjuvant temozolomide (TMZ) after surgery. | Biological: Nimotuzumab<br>* Nimotuzumab, 200 mg as 1-hour intravenous infusion once weekly, from first week to last week of RT for a total of 6 times.<br>Drug: Temozolomide<br>* Temozolomide, 75 mg/m2/d was administered orally from the first to the last day of RT. After 4-week break, individualized adjuvant TMZ was given based on MGMT status. The standard 5-day schedule every 4 weeks for six cycles was given for patients with negative MGMT expression. Dose was 150mg/m2 for the first cycle and 200 mg/m2 from the second cycle. The 7-day on/7-day off schedule every 2 weeks for 12 cycles was given for patients with positive MGMT expression. The dose was 100 mg/m2 for the first two cycles and 150 mg/m2 starting from the third cycle.<br>Radiation: Radiotherapy<br>* Fractionated 3D conformal RT was given at 2.0Gy per fraction, 5 daily fractions per week for 6 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | PFS will be calculated as the time from surgery to the date of progression-free. | 2 years | 
| Overall survival (OS) | OS will be calculated as the time from surgery to the date of death. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR: overall response rate (ORR), subjects will be classified according to the RANO criteria, which is a composite of MRI changes, clinical response and changes in steroid use. | 6 months | 
| Incidence of adverse events | Incidence of adverse events.Toxicities will be tabulated and graded according to the NCI Common Toxicity Criteria (CTCAE) version 3. | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
glioma, phase 2, nimotozumab, temozolomide, radiotherapy