Study of Post-Op Adjuvant Concurrent Chemo-RT With or Without Nimotuzumab for Head & Neck Cancer - Full Text View

Purpose

The aim of the study is to improve the loco-regional control rate and overall survival of locally advanced head and neck squamous carcinoma (HNSCC). The investigators hypothesize that the addition of nimotuzumab (a recombinant humanized murine immune antibody that blocks both epidermal growth factor (EGF) and transforming growth factor (TGF)) to the current gold standard of concurrent chemoradiotherapy (CCRT) (7)(8), an adjuvant setting in patients after resection of their locally advanced HNSCC will confer therapeutic advantage.

Condition	Intervention	Phase
Head & Neck Carcinoma	Drug: Nimotuzumab Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Phase III, Double-Blind, Placebo-Controlled Study of Post-Operative Adjuvant Concurrent Chemo-Radiotherapy With or Without Nimotuzumab for Stage III/IV Head & Neck Squamous Cell Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by National Cancer Centre, Singapore:

Primary Outcome Measures:

To compare the disease-free survival between patients randomized to adjuvant nimotuzumab/cisplatin/RT with the control arm [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To compare the overall survival between the two arms [ Time Frame: 5 years ] [ Designated as safety issue: No ]
To assess the Toxicity Profile between the 2 arms [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	710
Study Start Date:	August 2009
Estimated Study Completion Date:	June 2016
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Nimotuzumab Comprising Adjuvant Cisplatin, Concurrent RT and Nimotuzumab	Drug: Nimotuzumab Administered by intravenous infusion at 200 mg absolute per dose, diluted in 250 ml of sodium chloride over 30 minutes. 8 weekly doses of study drug will be given, beginning on first week of radiotherapy.
Placebo Comparator: Placebo Comprising Adjuvant Cisplatin, Concurrent RT and Placebo	Drug: Placebo Administered by intravenous infusion at 200 mg absolute per dose, diluted in 250 ml of sodium chloride over 30 minutes. 8 weekly doses of study drug will be given, beginning on first week of radiotherapy.

Detailed Description:

The aim of the study is to improve the loco-regional control rate and overall survival of locally advanced head and neck squamous carcinoma (HNSCC). We hypothesize that the addition of nimotuzumab (a recombinant humanized murine immune antibody that blocks both epidermal growth factor (EGF) and transforming growth factor (TGF)) to the current gold standard of concurrent chemoradiotherapy (CCRT) (7)(8), an adjuvant setting in patients after resection of their locally advanced HNSCC will confer therapeutic advantage. We have designed a phase III randomized study that includes a placebo arm. We assume a 10% increase in 2 year disease free survival (from 60% to 70%). To achieve statistical significance at 90% power, we calculate the need for 355 patients per arm, assuming also a 10% dropout rate. We aim to accomplish this study with the involvement of a multidisciplinary team of surgical, radiation and medical oncologists actively involved in the management of HNSCC coming from multiple institutions and spanning at least 12 different countries. For quality assurance we will have the involvement of Singapore Clinical Research Institute who will lead the data coordination and ensure fidelity of data collected and statistical analysis; the European Society of Therapeutic Radiation Oncology (EQUAL-ESTRO) for radiation dose and fields and an international independent panel of medical oncologist, radiation oncologist and biostatistician for the Data Monitoring Committee (DMC). This committee will monitor significant events and advise on continuation or termination of trial. Concurrent with the randomized trial, we will be collecting bio specimens including blood, tumour and saliva, pre-treatment and on completion of surgical resections. We hypothesize that there are important biomarkers including clusters of genes, cancer stem cells that will predict prognosis and treatment response. The analyses performed will be very powerful because of the large sample size, the specimens are collected prospectively and because the statistical analyses will be multivariate, incorporating not only treatment but biological and staging data.

Eligibility

Ages Eligible for Study:	21 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age less than or equal to 70 years old
Histologically proven head and neck squamous cell cancer (excluding nasopharynx, salivary glands, paranasal sinuses and unknown primaries) on biopsy of the primary lesion or the neck mass.
Resectable stage III/IV according to the AJCC/UICC staging system with no evidence of distant metastasis.
Complete macroscopic resection.
Patients should have at least one of the following pathological features for inclusion: pT3 or pT4 and any nodal stage (N), except T3N0 of the larynx, with negative resection margins, or a tumor stage of 1 or 2 with a nodal stage of 2 or 3 and no distant metastasis (M0); patients with stage T1 or T2 and N0 or N1 who had unfavorable pathological findings (extranodal spread, positive resection margins, perineural involvement, or vascular tumor embolism) are also eligible, as are those with oral-cavity or oropharyngeal tumors with involved lymph nodes at level IV or V.
Performance status must be ECOG 0 or 1. Patients should be able to tolerate chemotherapy and radiotherapy.
Adequate bone marrow, renal and hepatic function:
1. WBC>3000/mm3, platelets>100000/mm3
2. Serum creatinine<upper limit of normal range as per institution and calculated creatinine clearance (according to the Cockcroft and Gault method) >50 ml/min.
3. SAP, SGOT<2 x upper limit of normal range, bilirubin <1.5 x upper limit of normal range.
Written informed consent.

Exclusion Criteria:

Histology other than SCC or its subtype.
Patients with disease subsite deemed suitable for organ preservation approach, namely stage III/IV laryngeal or hypopharyngeal carcinoma with not more than low-volume T4 disease; low-volume T4 disease is defined as disease not eroding into cartilage or extending not more than 1 cm into the base of tongue.
Clinical or radiological evidence of distant metastasis.
Uncontrolled comorbidities such as diabetes mellitis, hypertension, cardiac disease.
Uncontrolled infection.
Uncontrolled hypercalcemia.
Prior history of cancer less than 5 years ago or a synchronous primary outside the head and neck area.
Prior treatment, head and neck radiotherapy, chemotherapy or surgery (excluding biopsy) or anti-EGFR therapy such as cetuximab/EGFR oral tyrosine kinase inhibitor.
Patients for whom compliance with follow-up is unlikely.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00957086

Contacts

Contact: K C Soo, Prof	64368000	admskc@nccs.com.sg
Contact: E H Tan, Dr	64368000	dmoteh@nccs.com.sg

Locations

Singapore
National Cancer Centre	Recruiting
Singapore, Singapore
Contact: K C Soo, Prof +65 64368000
Principal Investigator: K C Soo, Prof

Sponsors and Collaborators

National Cancer Centre, Singapore

National Medical Research Council (NMRC), Singapore

Innogene Kalbiotech Pte. Ltd

Investigators

Study Chair:

K C Soo, Prof

National Cancer Centre

More Information

No publications provided

Responsible Party:	Prof Soo Khee Chee, National Cancer Centre
ClinicalTrials.gov Identifier:	NCT00957086 History of Changes
Other Study ID Numbers:	IHN01
Study First Received:	August 11, 2009
Last Updated:	July 20, 2011
Health Authority:	Singapore: Health Sciences Authority

Keywords provided by National Cancer Centre, Singapore:

Phase III Post-Op Adjuvant Concurrent Chemo-RT for Head & Neck Cancer

Additional relevant MeSH terms:

Carcinoma
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

Neoplasms by Site
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013