Nimotuzumab Plus Radiotherapy With Concomitant and Adjuvant Temozolomide for Cerebral Glioblastoma

Sponsor

Biotech Pharmaceutical Co., Ltd. (Other)

Overall Status

Completed

CT.gov ID

NCT03388372

Collaborator

Sun Yat-sen University (Other)

Enrollment

Locations

Arm

79.1

Actual Duration (Months)

7.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma	Biological: Nimotuzumab Drug: Temozolomide Radiation: Radiotherapy	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

39 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 18, 2010

Actual Primary Completion Date :

Mar 23, 2017

Actual Study Completion Date :

Mar 23, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nimotuzumab plus RT and temozolomide. Nimotuzumab, administered once a week intravenously in addition to radiotherapy with concomitant and adjuvant temozolomide (TMZ) after surgery.	Biological: Nimotuzumab Nimotuzumab, 200 mg as 1-hour intravenous infusion once weekly, from first week to last week of RT for a total of 6 times. Drug: Temozolomide 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. Radiation: Radiotherapy Fractionated 3D conformal RT was given at 2.0Gy per fraction, 5 daily fractions per week for 6 weeks.

Arm

Intervention/Treatment

Experimental: Nimotuzumab plus RT and temozolomide.

Nimotuzumab, administered once a week intravenously in addition to radiotherapy with concomitant and adjuvant temozolomide (TMZ) after surgery.

Biological: Nimotuzumab

Nimotuzumab, 200 mg as 1-hour intravenous infusion once weekly, from first week to last week of RT for a total of 6 times.

Drug: Temozolomide

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.

Radiation: Radiotherapy

Fractionated 3D conformal RT was given at 2.0Gy per fraction, 5 daily fractions per week for 6 weeks.

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) [2 years]
PFS will be calculated as the time from surgery to the date of progression-free.
Overall survival (OS) [2 years]
OS will be calculated as the time from surgery to the date of death.

Secondary Outcome Measures

Objective Response Rate (ORR) [6 months]
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.
Incidence of adverse events [6 months]
Incidence of adverse events.Toxicities will be tabulated and graded according to the NCI Common Toxicity Criteria (CTCAE) version 3.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong	China	510060
2	Guangdong Brain Hospital	Guangdong		China
3	The First Affiliated Hospital/School of Clinical Medicine of Guangdong	Guangdong		China
4	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou		China
5	Shenzhen People's Hospital	Shenzhen		China