Study of Post-Op Adjuvant Concurrent Chemo-RT With or Without Nimotuzumab for Head & Neck Cancer
- Conditions
- Carcinoma, Squamous Cell of Head and Neck
- Interventions
- Drug: Placebo
- Registration Number
- NCT00957086
- Lead Sponsor
- National Cancer Centre, Singapore
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 710
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Age should be greater than or equal to the minimum age of consent in the applicable country
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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.
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Resectable stage III/IV according to the AJCC/UICC staging system with no evidence of distant metastasis.
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Complete macroscopic resection.
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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.
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Performance status must be ECOG 0 or 1. Patients should be able to tolerate chemotherapy and radiotherapy.
-
Adequate bone marrow, renal and hepatic function:
- WBC>3000/mm3, platelets>100000/mm3
- Serum creatinine<upper limit of normal range as per institution and calculated creatinine clearance (according to the Cockcroft and Gault method) >50 ml/min.
- SAP, SGOT<2 x upper limit of normal range, bilirubin <1.5 x upper limit of normal range.
-
Written informed consent.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Placebo Placebo Comprising Adjuvant Cisplatin, Concurrent RT and Placebo Nimotuzumab Nimotuzumab Comprising Adjuvant Cisplatin, Concurrent RT and Nimotuzumab
- Primary Outcome Measures
Name Time Method To compare the disease-free survival between patients randomized to adjuvant nimotuzumab/cisplatin/RT with the control arm 5 years
- Secondary Outcome Measures
Name Time Method To compare the overall survival between the two arms 5 years To assess the Toxicity Profile between the 2 arms 5 years
Trial Locations
- Locations (30)
National Cancer Center Korea
🇰🇷Gyeonggi-do, Korea, Republic of
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Australia
Flinders Medical Centre
🇦🇺Bedford Park, Australia
Christian Medical College
🇮🇳Tamil Nadu, India
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
The Oncology Centre
🇿🇦Durban, South Africa
Cipto Mangunkusumo General Hospital Indonesia
🇮🇩Jakarta, Indonesia
GVI Oncology
🇿🇦Panorama, South Africa
Mahkota Medical Center
🇲🇾Melaka, Malaysia
St. Luke's Medical Center
🇵🇭Quezon City, Philippines
INHA University Hospital
🇰🇷Incheon, Korea, Republic of
National Cancer Centre
🇸🇬Singapore, Singapore
China Medical University Hospital
🇨🇳Taichung, Taiwan
National Cancer Institute, Cairo University
🇪🇬Cairo, Egypt
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
University of Santo Tomas Hospital
🇵🇭Manila, Philippines
National Cancer Institute Bangkok (+Chulabhorn for RT)
🇹🇭Bangkok, Thailand
Alexandria University School of Medicine
🇪🇬Alexandria, Egypt
King Fahad Medical City
🇸🇦Riyadh, Saudi Arabia
Chiang Mai Hospital
🇹🇭Chiang Mai, Thailand
National Institute of Oncology and Radiobiology
🇨🇺Vedado, Cuba
Pantai Medical Centre, Kuala Lumpur
🇲🇾Kuala Lumpur, Malaysia
Siriraj Hospital
🇹🇭Bangkok, Thailand
Apollo Hospital Bangalore
🇮🇳Bangalore, India
Tata Memorial Centre
🇮🇳Mumbai, India
Taipei Med Univ Hosp [TMUH]
🇨🇳Taipei, Taiwan
Narayana Hrudayalaya Hospital (Mazumdar Shaw Cancer Institute)
🇮🇳Bangalore, India
Amrita Institute of Medical Sciences
🇮🇳Kerala, India
Regional Cancer Center Trivandrum, India
🇮🇳Trivandrum, India
Taipei Veteran General Hospital
🇨🇳Taipei, Taiwan