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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

Phase 3
21 Years
70 Years
Open (Enrolling)
Head & Neck Carcinoma

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Trial Information

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). 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

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 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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

To compare the disease-free survival between patients randomized to adjuvant nimotuzumab/cisplatin/RT with the control arm

Outcome Time Frame:

5 years

Safety Issue:


Principal Investigator

K C Soo, Prof

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Centre


Singapore: Health Sciences Authority

Study ID:




Start Date:

August 2009

Completion Date:

June 2016

Related Keywords:

  • Head & Neck Carcinoma
  • Phase III Post-Op Adjuvant Concurrent Chemo-RT for Head & Neck Cancer
  • Carcinoma
  • Neoplasms, Squamous Cell
  • Head and Neck Neoplasms