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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma, Squamous Cell of Head and Neck
• Intervention / Treatment: Drug: Nimotuzumab; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 710
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia
    • Flinders Medical Centre
  • Melbourne, Australia, VIC 3002
    • Peter MacCallum Cancer Centre
• Cuba
  • Vedado, Cuba
    • National Institute of Oncology and Radiobiology
• Egypt
  • Alexandria, Egypt
    • Alexandria University School of Medicine
  • Cairo, Egypt
    • National Cancer Institute, Cairo University
• India
  • Bangalore, India
    • Apollo Hospital Bangalore
  • Bangalore, India
    • Narayana Hrudayalaya Hospital (Mazumdar Shaw Cancer Institute)
  • Kerala, India
    • Amrita Institute of Medical Sciences
  • Mumbai, India
    • Tata Memorial Centre
  • Tamil Nadu, India
    • Christian Medical College
  • Trivandrum, India
    • Regional Cancer Center Trivandrum, India
• Indonesia
  • Jakarta, Indonesia
    • Cipto Mangunkusumo General Hospital Indonesia
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of
    • National Cancer Center Korea
  • Incheon, Korea, Republic of
    • Inha University Hospital
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University Health System
• Malaysia
  • Kuala Lumpur, Malaysia
    • Pantai Medical Centre, Kuala Lumpur
  • Melaka, Malaysia
    • Mahkota Medical Center
• Philippines
  • Manila, Philippines
    • University of Santo Tomas Hospital
  • Quezon City, Philippines
    • St. Luke's Medical Center
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • King Fahad Medical City
• Singapore
  • Singapore, Singapore
    • National Cancer Centre
• South Africa
  • Durban, South Africa
    • The Oncology Centre
  • Panorama, South Africa
    • GVI Oncology
• Taiwan
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taipei, Taiwan
    • Taipei Veteran General Hospital
  • Taipei, Taiwan
    • Taipei Med Univ Hosp [TMUH]
• Thailand
  • Bangkok, Thailand
    • Siriraj Hospital
  • Bangkok, Thailand
    • National Cancer Institute Bangkok (+Chulabhorn for RT)
  • Chiang Mai, Thailand
    • Chiang Mai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To compare the disease-free survival between patients randomized to adjuvant nimotuzumab/cisplatin/RT with the control arm	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To compare the overall survival between the two arms	5 years
To assess the Toxicity Profile between the 2 arms	5 years

Collaborators and Investigators

• Sponsor: National Cancer Centre, Singapore
• Collaborators: National Medical Research Council (NMRC), Singapore; Innogene Kalbiotech Pte. Ltd
• Investigators: Study Chair: K C Soo, Prof, National Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2009
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: August 11, 2009
• First Submitted That Met QC Criteria: August 11, 2009
• First Posted (Estimated): August 12, 2009

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Phase III Adjuvant Concurrent Chemo-RT +/- nimotuzumab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Antineoplastic Agents, Immunological; Nimotuzumab
• Other Study ID Numbers: IHN01