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

NCT ID: NCT00957086

Last Updated: 2024-01-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 710 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-13
• Study Completion Date: 2025-01-01

Brief Summary

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.

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.

Conditions

Carcinoma, Squamous Cell of Head and Neck

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Nimotuzumab

Comprising Adjuvant Cisplatin, Concurrent RT and Nimotuzumab

Group Type: ACTIVE_COMPARATOR

Nimotuzumab

Intervention Type: DRUG

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

Comprising Adjuvant Cisplatin, Concurrent RT and Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age should be greater than or equal to the minimum age of consent in the applicable country
• 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.

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Medical Research Council (NMRC), Singapore

OTHER_GOV

Sponsor Role: collaborator

Innogene Kalbiotech Pte. Ltd

INDUSTRY

Sponsor Role: collaborator

National Cancer Centre, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

K C Soo, Prof

Role: STUDY_CHAIR

National Cancer Centre

Locations

Flinders Medical Centre

Bedford Park, , Australia

Peter MacCallum Cancer Centre

Melbourne, , Australia

National Institute of Oncology and Radiobiology

Vedado, , Cuba

Alexandria University School of Medicine

Alexandria, , Egypt

National Cancer Institute, Cairo University

Cairo, , Egypt

Apollo Hospital Bangalore

Bangalore, , India

Narayana Hrudayalaya Hospital (Mazumdar Shaw Cancer Institute)

Bangalore, , India

Amrita Institute of Medical Sciences

Kerala, , India

Tata Memorial Centre

Mumbai, , India

Christian Medical College

Tamil Nadu, , India

Regional Cancer Center Trivandrum, India

Trivandrum, , India

Cipto Mangunkusumo General Hospital Indonesia

Jakarta, , Indonesia

Pantai Medical Centre, Kuala Lumpur

Kuala Lumpur, , Malaysia

Mahkota Medical Center

Malacca, , Malaysia

University of Santo Tomas Hospital

Manila, , Philippines

St. Luke's Medical Center

Quezon City, , Philippines

King Fahad Medical City

Riyadh, , Saudi Arabia

National Cancer Centre

Singapore, , Singapore

The Oncology Centre

Durban, , South Africa

GVI Oncology

Panorama, , South Africa

National Cancer Center Korea

Gyeonggi-do, , South Korea

INHA University Hospital

Incheon, , South Korea

Samsung Medical Center

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

China Medical University Hospital

Taichung, , Taiwan

Taipei Med Univ Hosp [TMUH]

Taipei, , Taiwan

Taipei Veteran General Hospital

Taipei, , Taiwan

National Cancer Institute Bangkok (+Chulabhorn for RT)

Bangkok, , Thailand

Siriraj Hospital

Bangkok, , Thailand

Chiang Mai Hospital

Chiang Mai, , Thailand

Countries

Australia; Cuba; Egypt; India; Indonesia; Malaysia; Philippines; Saudi Arabia; Singapore; South Africa; South Korea; Taiwan; Thailand

Other Identifiers

IHN01

Identifier Type: -

Identifier Source: org_study_id