Nimotuzumab in Combination With Radio-chemotherapy for the Treatment of Brainstem Tumor in Children

Sponsor

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (Other)

Overall Status

Unknown status

CT.gov ID

NCT02672241

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of nimotuzumab in combination of radio-chemotherapy for the treatment of brainstem tumor in children.

Condition or Disease	Intervention/Treatment	Phase
Childhood Brain Stem Neoplasm	Drug: Nimotuzumab Drug: Temozolomide	Phase 2

Detailed Description

Nimotuzumab (h-R3), a recombinant humanized monoclonal immunoglobulin G1 antibody that binds to the extracellular domain of EGFR, which blocks the binding of EGF and transforming growth factor-α to EGFR. High expression of EGFR protein in glioma has been associated with tumor progression and enhanced tumorigenicity. Several clinical trials have demonstrated the anti-tumor effects of nimotuzumab, such as head and neck cancer and esophageal cancer15. The purpose of this study was to evaluate the efficacy of nimotuzumab in combination of radio-chemotherapy for the treatment of brainstem tumors in children.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 2 Study of Nimotuzumab in Combination With Radio-chemotherapy for the Treatment of Brainstem Tumor in Children

Study Start Date :

Jan 1, 2016

Anticipated Primary Completion Date :

Aug 1, 2019

Anticipated Study Completion Date :

Aug 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: radio-chemotherapy plus nimotuzumab Radiotherapy: The total radiation dose is 52.2Gy (1.8Gy fractions). Chemotherapy: Nimotuzumab, given during radiotherapy, is administered via intravenous drip with a dosage of 150mg/m2, weekly, for 6 consecutive weeks. After radiotherapy and evaluation, disease progression-free patients will continue to receive Nimotuzumab treatment biweekly until disease relapse or progression. Temozolomide is applied to these patients as a chemotherapy drug with a dosage of 75mg/m2, daily. The chemotherapy and radiation therapy are combined as temozolomide is taken 1 hour prior to every fraction of radiotherapy. In 4 weeks after the completion of radiotherapy, temozolomide is given for 8 cycles.	Drug: Nimotuzumab Nimotuzumab given during radiotherapy, is administered via intravenous drip with a dosage of 150mg/m2, weekly, for 6 consecutive weeks. After radiotherapy and evaluation, disease progression-free patients will continue to receive Nimotuzumab treatment biweekly until disease relapse or progression. Other Names: h-R3, BIOMAb EGFR, Biocon Drug: Temozolomide Temozolomide is applied to these patients as a chemotherapy drug with a dosage of 75mg/m2, daily. The chemotherapy and radiation are combined as temozolomide is taken 1 hour prior to every fraction of radiotherapy. In 4 weeks after the completion of radiotherapy, temozolomide is given for 8 cycles (dosage: the 1st cycle, 150mg/m2, daily × 5 days, 4 weeks a cycle; the 2-8th cycle, 200mg/m2, daily × 5 days, 4 weeks a cycle and repeated again). Other Names: brand names Temodar and Temodal and Temcad

Arm

Intervention/Treatment

Experimental: radio-chemotherapy plus nimotuzumab

Radiotherapy: The total radiation dose is 52.2Gy (1.8Gy fractions). Chemotherapy: Nimotuzumab, given during radiotherapy, is administered via intravenous drip with a dosage of 150mg/m2, weekly, for 6 consecutive weeks. After radiotherapy and evaluation, disease progression-free patients will continue to receive Nimotuzumab treatment biweekly until disease relapse or progression. Temozolomide is applied to these patients as a chemotherapy drug with a dosage of 75mg/m2, daily. The chemotherapy and radiation therapy are combined as temozolomide is taken 1 hour prior to every fraction of radiotherapy. In 4 weeks after the completion of radiotherapy, temozolomide is given for 8 cycles.

Drug: Nimotuzumab

Nimotuzumab given during radiotherapy, is administered via intravenous drip with a dosage of 150mg/m2, weekly, for 6 consecutive weeks. After radiotherapy and evaluation, disease progression-free patients will continue to receive Nimotuzumab treatment biweekly until disease relapse or progression.

Other Names:

h-R3, BIOMAb EGFR, Biocon

Drug: Temozolomide

Temozolomide is applied to these patients as a chemotherapy drug with a dosage of 75mg/m2, daily. The chemotherapy and radiation are combined as temozolomide is taken 1 hour prior to every fraction of radiotherapy. In 4 weeks after the completion of radiotherapy, temozolomide is given for 8 cycles (dosage: the 1st cycle, 150mg/m2, daily × 5 days, 4 weeks a cycle; the 2-8th cycle, 200mg/m2, daily × 5 days, 4 weeks a cycle and repeated again).

Other Names:

brand names Temodar and Temodal and Temcad

Outcome Measures

Primary Outcome Measures

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [first analysis will occur 1 month after accrual of all patients]

Secondary Outcome Measures

Progression free survival(PFS) [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months]
Overall survival (OS) [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months]
Objective response rate (ORR) [first analysis will occur 1 month after accrual of all patients]

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 12 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must be >/= 3 and </= 21 years of age.
Patients must have a newly diagnosed or progressive brain stem tumor.
If biopsy has been performed, patients with both high and low grade astrocytomas are eligible.
Non-histologically confirmed brain stem tumors are eligible. Neuroradiographic confirmation of brain stem glioma is mandatory for study entry.
Cervicomedullary junction tumors are ineligible.
Patients with a diagnosis of NF-1 are ineligible.
Patients must be registered within 6 weeks from diagnosis or recurrence.
Patients must have life expectancy > 6 weeks.
Patients must have adequate hematologic and renal function: ANC >1,000/ul, platelets>100,000/ul and creatinine normal for age: </= 0.7 mg/dl (age 3-10yrs.), </= 1.0 mg/dl (11-12yrs.). and </= 1.2 (13-21yrs.).
Written informed consent must be obtained according to institutional guidelines.

Exclusion Criteria:

Cervicomedullary junction tumors are ineligible.
Patients with a diagnosis of NF-1 are ineligible.
Pregnant or nursing women are ineligible.
Patients must not start treatment until informed consent is given and the patient is registered.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	he Department of Radiation Oncology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai	China	200092

Sponsors and Collaborators

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Investigators

Principal Investigator: mawei jiang, MD, The Department of Radiation Oncology, Xin Hua Hospital affiliated to Shanghai Jiaotong University School of Medicine