Study of Nimotuzumab and Cisplatin/Radiotherapy for Locally Advanced Head and Neck Squamous Cell Cancer

Sponsor

National Cancer Centre, Singapore (Other)

Overall Status

Unknown status

CT.gov ID

NCT00702481

Collaborator

Innogene Kalbiotech Pte. Ltd (Industry)

Enrollment

Location

Arm

140

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to define the response and toxicities with the addition of Nimotuzumab to chemoradiation for head and neck cancer.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: Nimotuzumab Drug: Cisplatin Radiation: Radiation	Phase 2

Detailed Description

Epidermal Growth Factor Receptor (EGFR) is overexpressed in Head and Neck Squamous Cell Carcinoma (HNSCC). EGFR pathway activation is associated with tumor growth, decreased apoptosis, and increased angiogenesis. These present a putative target for the use of EGFR inhibitors either in the form of small molecule inhibitors or monoclonal antibodies. Several studies have been advanced that suggest application of these targeted therapies show promising responses with little additional toxicity. The addition of EGFR monoclonal antibodies to radiation results in better response rates and locoregional control compared to radiation alone. Addition of EGFR monoclonal antibodies compared to chemotherapy alone also improves the response rates in patients with advanced HNSCC.

Nimotuzumab is a humanized chimeric monoclonal antibody specific to the extracellular domain of EGFR. Several studies are ongoing and demonstrate promising efficacy of Nimotuzumab as monotherapy and in combination with radiation in HNSCC, and in combination with chemoradiation in Nasopharyngeal Carcinoma. This phase II clinical trial examines the feasibility of EGFR inhibition using Nimotuzumab in combination with concurrent chemoradiotherapy in locally advanced unresectable HNSCC. Successful and safe incorporation of an EGFR monoclonal antibody into the concurrent chemoradiation paradigm used to treat locally advanced HNSCC will represent an important advance in the optimisation of treatment for this group of patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Study of Nimotuzumab (TheraCim-hR3) Concurrent With Cisplatin/Radiotherapy in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)

Study Start Date :

Apr 1, 2008

Anticipated Primary Completion Date :

Dec 1, 2019

Anticipated Study Completion Date :

Dec 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nimotuzumab/CDDP/RT Open label treatment arm of Nimotuzumab and cisplatin and radiation	Drug: Nimotuzumab Patients will receive nimotuzumab 200 mg weekly for 8 weeks. Nimotuzumab will be started together with concurrent chemoradiation, and continued 1 week after the completion of chemoradiation. Other Names: TheraCim-Rh3 Drug: Cisplatin Concurrent chemotherapy with cisplatin 100 mg/m2 will be given on week 1, 4, and 7 of radiotherapy. Radiation: Radiation Concurrent radiotherapy will be given to the primary tumor and upper neck at 2 Gy per fraction, once a day, five days a week to a total of 70 Gy in 35 fractions in seven weeks.

Arm

Intervention/Treatment

Experimental: Nimotuzumab/CDDP/RT

Open label treatment arm of Nimotuzumab and cisplatin and radiation

Drug: Nimotuzumab

Patients will receive nimotuzumab 200 mg weekly for 8 weeks. Nimotuzumab will be started together with concurrent chemoradiation, and continued 1 week after the completion of chemoradiation.

Other Names:

TheraCim-Rh3

Drug: Cisplatin

Concurrent chemotherapy with cisplatin 100 mg/m2 will be given on week 1, 4, and 7 of radiotherapy.

Radiation: Radiation

Concurrent radiotherapy will be given to the primary tumor and upper neck at 2 Gy per fraction, once a day, five days a week to a total of 70 Gy in 35 fractions in seven weeks.

Outcome Measures

Primary Outcome Measures

To determine the response rate of locally advanced HNSCC to treatment with Nimotuzumab and concurrent Cisplatin (CDDP) and Radiotherapy (RT). [16 weeks]

Secondary Outcome Measures

To assess the toxicities associated with this regimen [16 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed Squamous Cell Carcinoma of the Head and Neck.
Locally advanced disease, unresectable disease or resectable disease where organ-preservation is intended
Age > 18 years
Adequate performance status of ECOG 0-2
Life expectancy of at least 3 months
Written informed consent to participate in the study
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
Patients must have normal organ and marrow function as defined below:
leukocytes >3,000/uL
absolute neutrophil count >1,500/uL
platelets >100,000/uL
total bilirubin within normal institutional limits
AST(SGOT)/ALT(SGPT) < 2.5X normal . Creatinine within normal range and CCT(Cockcroft-Gault) > 50 ml/min

Exclusion Criteria:

Prior treatment with anti-EGFR or chemotherapy/radiotherapy
Evidence of CNS metastases
Poor performance status (ECOG 3-4)
Evidence of severe or uncontrolled systemic disease (eg. unstable or uncompensated respiratory disorder, cardiac failure, hepatic decompensation, renal failure, nephritic syndrome, uncontrolled metabolic disorders such as diabetes mellitus, uncontrolled hypertension or uncontrolled significant infections)
Pregnancy or breast-feeding (women of child-bearing potential)
Prior severe allergic drug reactions
Prior history of cancer in the last 5 years prior to enrollment, other than curatively treated cancer of the cervix or non-melanoma skin cancer.