UMIN-CTR Clinical Trial

Public title

The efficacy of postoperative bio-chemoradiotherapy using cetuximab and docetaxel for cis-platinum intolerant high-risk head and neck cancer patients.

Acronym

The efficacy of postoperative B-CRT using Cmab and DTX for CDDP intolerant high-risk head and neck cancer patients.

Scientific Title

The efficacy of postoperative bio-chemoradiotherapy using cetuximab and docetaxel for cis-platinum intolerant high-risk head and neck cancer patients.

Scientific Title:Acronym

The efficacy of postoperative B-CRT using Cmab and DTX for CDDP intolerant high-risk head and neck cancer patients.

Region

Japan

Condition

The efficacy of postoperative bio-chemoradiotherapy using cetuximab and docetaxel for cis-platinum intolerant high-risk head and neck cancer patients.

Classification by specialty

Oto-rhino-laryngology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

For the advanced head and neck cancer patients, surgery is a common definitive therapy. After surgery, pathological evaluation is necessary for the decision of additional therapy. The pathological results of microscopically involved surgical margin of the primary site and/or extracapsular extension of the lymph nodes are considered to be core high-risk factors indicating poor prognosis. The outcome for patients with these high-risk factors may be improved by concurrent chemotherapy in additional administration during postoperative radiotherapy. The standard protocol for the postoperative chemoradiotherapy is the concurrent use of cis-platinum (CDDP) during radiotherapy for previous described high-risk patients. However, many of these patients are intolerant to CDDP, and one option to overcome these problems is the combined administration of cetuximab (Cmab) and docetaxel (DTX) during postoperative radiotherapy. We tried combination use of Cmab and DTX during postoperative radiotherapy for CDDP intolerant high-risk head and neck cancer patients in limited number and revealed the safety. Here we propose this trial to confirm the efficacy of postoperative bio-chemoradiotherapy using Cmab and DTX for CDDP intolerant high-risk head and neck cancer patients.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

2-year disease free survival

Key secondary outcomes

2-year overall survival, 2-year recurrence free survival, and 2-year locoregional control survival

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Radiotherapy is delivered in conventional fractions of 1.8 Gy to a total dose of 66.6 Gy, 5 days per week, using 4-6 MV X-rays. The radiation fields are set up as the primary tumor and, prophylactically, the bilateral cervical lymph node area. The cervical lymph node area is received prophylactic doses of 45 Gy with lateral opposed fields to upper neck and anterior lower neck. The bio-chemotherapy regimen consists of weekly Cmab (week 1: 400mg/m2; subsequent weeks: 250 mg/m2) and DTX (25mg/m2).

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Prior to enrollment in this trial, the patients must meet all of the following criteria: pathologically proven carcinoma; primary tumor located in the nasal/paranasal sinus, oral cavity, larynx, oropharynx and hypopharynx; clinically advanced stage (stage III or IV) on visual and endoscopic examinations and imaging examinations; e.g., CT, magnetic resonance imaging (MRI), ultrasonic echo (US) and/or PET-CT; primary site assessed as resectable by definitive surgery and regional lymph node by neck dissection on CT, MRI and/or US; no distant metastasis on PET-CT (cM0); aged over 20 years old (regarded as legally adult in Japan); PS 0-2 on ECOG criteria; sufficient general condition for the operation under general anesthesia; CDDP intolerant; e.g., advanced age (over 75-year-old), poor renal function (e-GFR < 60 ml/min/1.73m2), insufficient bone marrow function (white blood cell count < 3,000/mm3, neutrophil count < 1,500/mm3, platelet count < 7.5x104/mm3), hearing impairment, drug allergy, past history of CDDP use and/or poor general condition; and provision of written informed consent.

Key exclusion criteria

Prior to enrollment in this trial, the patients must not meet any of the following criteria: uncurable synchronous malignancies, priority systemic diseases, and refusal to undergo the definitive surgery and/or postoperative radiotherapy.

Target sample size

35

Name of lead principal investigator

1st name	Nobuhiko
Middle name
Last name	Oridate

Organization

Yokohama City University, School of Medicine

Division name

Department of Otorhinolaryngology, Head and Neck Surgery

Zip code

236-0004

Address

3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004

TEL

045-787-2687

Email

noridate@yokohama-cu.ac.jp

Name of contact person

1st name	Goshi
Middle name
Last name	Nishimura

Organization

Yokohama City University, School of Medicine

Division name

Department of Otorhinolaryngology, Head and Neck Surgery

Zip code

236-0004

Address

3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004

TEL

045-787-2687

Homepage URL

Email

gnishimu@yokohama-cu.ac.jp

Institute

Yokohama City University Hospital

Institute

Department

Personal name

Organization

Yokohama City University Hospital

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Yokohama City University

Address

3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004

Tel

045-370-7627

Email

rinri@yokohama-cu.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2018

Year

04

Month

01

Day

URL releasing protocol

https://center6.umin.ac.jp/cgi-open-bin/ctr/index.cgi

Publication of results

Unpublished

URL related to results and publications

Examination Cancellation

Number of participants that the trial has enrolled

0

Results

No subscribers, no track record

Results date posted

2025

Year

09

Month

26

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

When treating pharyngeal and laryngeal cancer, the ideal outcome is achieving both a cure for the disease and preserving functions such as speech and swallowing. Surgery has developed as the primary treatment method when the focus is on curing the disease, while radiation therapy has evolved as the main approach when the emphasis is on preserving function. However, considering the collateral damage associated with treatment, current methods still have room for improvement in simultaneously achieving cure and function preservation.

Participant flow

This study included patients deemed eligible for TOVS as initial therapy and, if present, for neck dissection (primarily T1-2 cases of laryngeal, oropharyngeal, and hypopharyngeal cancer, with resectable N stages) who were deemed suitable for TOVS as initial therapy and also eligible for neck dissection due to cervical lymph node metastasis. Based on postoperative pathological findings, patients were assigned to either the observation group (negative primary tumor resection margins and negative extranodal lymph node involvement in the neck) or the postoperative radiotherapy group (positive or suspected positive primary tumor resection margins and/or positive extranodal lymph node involvement in the neck) for prognostic follow-up.

Adverse events

Adverse events associated with general surgery include pain, infection, bleeding, and symptoms related to general anesthesia. Adverse events associated with TOVS surgery include dysarthria/dysphonia, oral intake impairment, and airway stenosis. Adverse events associated with rare-site dissection include neck pain and upper arm mobility restriction. Adverse events associated with radiation therapy include early effects (stomatitis, dermatitis, edema, etc.) and late effects (salivary secretion impairment, dysphagia, etc.).
Recent years have seen remarkable advances in supportive equipment for cancer treatment. One such development is the video laryngoscope. Surgery for pharyngeal and laryngeal cancer, previously performed using the naked eye or surgical microscopes, now enables more precise observation and strict resection using high-precision endoscopic systems (transoral videolaryngoscopi surgery, TOVS). The surgery involves inserting a video laryngoscope through the mouth for observation and resection. Since the pharynx and larynx occupy a limited space, this procedure is generally indicated for early-stage primary cancers. If cervical lymph node metastasis is present, neck dissection is performed either on the same day or at a later date.
Under conventional treatment guidelines, radiation therapy is used when early-stage cancer is confined to the primary tumor. For advanced cancer where the primary tumor has progressed or metastasis is present in the cervical lymph nodes, extended surgery with reconstruction or radiation therapy combined with chemotherapy is performed. Radiation therapy carries significant burdens for patients, including salivary secretion disorders and muscle stiffness from the neck to the shoulders. Surgery involving reconstruction carries disadvantages such as loss of voice and impaired swallowing function due to laryngectomy. Furthermore, patients requiring such extensive surgery often undergo radiation therapy postoperatively. While generally milder than radiation therapy combined with chemotherapy, this can still cause reduced saliva production and restricted mobility in the neck and shoulder area.
TOVS is a treatment method that aims to achieve both curative potential and functional preservation by excising the primary tumor at the minimum necessary size to avoid these drawbacks. However, disadvantages of TOVS include that surgical indications are generally limited to early-stage primary cancers, and the limited surgical space may result in inadequate visualization or resection in some areas. Following treatment guidelines traditionally advocated in Europe and the US, the need for postoperative radiation therapy is determined based on the pathological examination results of the surgical specimen. The criteria proposed by the US RTOG or the European EORTC are globally recognized standards for determining the need for postoperative radiation therapy in head and neck cancer. However, these criteria include both common and non-common items. When explaining TOVS eligibility to patients, the goal is to achieve curative intent and preserve function using TOVS alone, while maximally avoiding the disadvantages associated with radiation therapy. However, it is a fact that a certain proportion of patients will require postoperative radiation therapy: failing to provide necessary treatment for these patients would also be detrimental to them. In this study, we considered the common items from the criteria proposed by the aforementioned institutions to be the core of eligibility. Therefore, postoperative radiation therapy is added only in the following two cases:1) When the resection margin of the primary tumor removed by TOVS is inadequate (however, if complete resection is deemed possible by performing TOVS again, additional resection may be prioritized), and 2) When metastatic lymph nodes in patients who underwent neck dissection showed extralymphatic infiltration. For all other patients, continued additional radiotherapy after surgery is deemed unnecessary. Regardless of which group a patient belongs to, standard follow-up care, including regular examinations, various tests, and additional treatment in case of recurrence, is performed equally. This study aims to rigorously restrict postoperative radiotherapy and confirm whether the disease can be managed with surgery alone.

Outcome measures

Disease-free survival period

Plan to share IPD

IPD sharing Plan description

Recruitment status

Enrolling by invitation

Date of protocol fixation

2018

Year

03

Month

05

Day

Date of IRB

2018

Year

03

Month

05

Day

Anticipated trial start date

2018

Year

04

Month

01

Day

Last follow-up date

2023

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

03

Month

22

Day

Last modified on

2025

Year

09

Month

26

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000036355