Condition category
Cancer
Date applied
05/10/2015
Date assigned
26/10/2015
Last edited
26/10/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Mouth cancer is the most common type of cancer that affects the head and neck area. About 90% of all mouth cancers start in the thin, flat cells which line the lips and the inside of the mouth (squamous cells) and are known as oral squamous cell carcinoma (OSCC). If OSCC is found early, then in most cases a complete cure is possible using a combination of chemotherapy, radiotherapy and surgery. If it is left untreated however, then it can spread very quickly to other areas of the mouth, head and neck. If the tumour is small enough, then it can be completely removed in an operation. If the tumour is inoperable however, patients tend to have a worse outlook, and more aggressive chemotherapy is often needed. Cetuximab is a medication which is used to treat advanced cancer of the head and neck. It belongs to a group of drugs called monoclonal antibodies, which work by “locking onto” specific proteins (receptors) on the surface of the cancer cells, preventing them from multiplying. The first-line drug treatment (induction chemotherapy) for head and neck cancers is usually TPF treatment, which is the name of a combination of chemotherapy medications (docetaxel, cisplatin and fluorouracil). Although cetuximab is usually only used in the late stages of head and neck cancer, it could potentially be incorporated into the TPF treatment (C-TPF) in induction chemotherapy. If this proves successful, then later radiotherapy (treatment to destroy cancer cells with radiation) could be more successful. The aim of this study is to find out whether C-TPF is an effective induction treatment for inoperable oral squamous cell carcinoma.

Who can participate?
Adults with inoperable oral squamous cell carcinoma where the cancerous cells have spread.

What does the study involve?
All participants are given two complete cycles of C-TPF treatment. This involves weekly treatment with cetuximab, docetaxel, cisplatin and fluorouracil administered intravenously (through a drip). After completing the treatment, participants have an MRI scan in order to find out whether the treatment has had any effect on the tumour size. Any participants who have responded to the C-TPF treatment are then given bio-chemoradiotherapy (bio-CRT), which involves radiotherapy and weekly treatment with cetuximab and cisplatin for a further 7 weeks. At the end of the bio-CRT treatment, participants attend monthly follow-up clinic visits. Participants are given another MRI scan two months after the bio-CRT treatment has ended, which is repeated every three months until the disease gets worse (disease progression) or the patient dies.

What are the possible benefits and risks of participating?
A benefit of participating is that patients can receive the new combinational treatment (C-TPF), which may prove to be a more effective treatment. The risks include the side effects from both cetuximab and TPF, which should be manageable.

Where is the study run from?
Taipei Veterans General Hospital (Taiwan)

When is the study starting and how long is it expected to run for?
April 2011 to May 2015

Who is funding the study?
1. Taiwan Clinical Oncology Research Foundation (Taiwan)
2. Taipei Veterans General Hospital (Taiwan)
3. Ministry of Health and Welfare (Taiwan)

Who is the main contact?
Dr Muh Hwa Yang

Trial website

Contact information

Type

Public

Primary contact

Prof Muh Hwa Yang

ORCID ID

Contact details

Taipei Veterans General Hospital
No. 201
Sec. 2
Shih-Pai Road
Taipei city
112
Taiwan

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

C-TPF (cetuximab, cisplatin, docetaxel, 5-FU) induction chemotherapy in inoperable squamous cell carcinoma of oral cavity: a phase II study

Acronym

Study hypothesis

C-TPF will be an effective induction treatment for inoperable oral squamous cell carcinoma.

Ethics approval

Institutional Review Board of Taipei Veterans General Hospital, 05/11/2015, ref: 2010-08-028 MB

Study design

Single-arm prospective open label phase II study

Primary study design

Interventional

Secondary study design

Non-comparative open labelled phase II study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Oral Squamous Cell Carcinoma

Intervention

All participants receive two cycles of C-TPF induction treatment. After completing the induction, MRI will be examined for the response of the treatment. Only complete or partial response participants will enter following bio-CRT. At the end of the bio-CRT, all participants will attend a follow-up visit every month at physicians' clinics. The first MRI image will be taken 2 months after completing the bio-CRT then every 3 months until disease progression or patient death.

Induction chemotherapy (C-TPF):
IC consisted of weekly cetuximab plus tri-weekly TPF twice for a total of seven weeks. Cetuximab was administered at a loading dose of 400 mg/m2 over a period of 120 minutes during the first week, followed by weekly 60-minute infusions of 250 mg/m2 for six weeks. A total of 7 courses of cetuximab were given during the induction phase. The tri-weekly TPF regimen was docetaxel 60 mg/m2 as a 3-hour intravenous infusion, followed by intravenous cisplatin 75 mg/m2 for a period of 3 hours and a 96-hour continuous infusion of fluorouracil at 850 mg/m2 per 24 hours. A total of 2 courses of TPF were given during the induction phase.

Bio-chemoradiotherapy (bio-CRT)
The definitive curative radiation dose administered to the primary tumor was 70 Gy, which was administered as fractions of 2 Gy per day, 5 days per week. The dose administered to uninvolved lymph nodes was between 44-60 Gy. Involved lymph nodes received 60-66 Gy. Radiotherapy must have been given with either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated RT (IMRT) techniques. Bio-chemotherapy was administered by a 60-minute infusion of 250 mg/m2 cetuximab weekly plus 60-minute infusions of 30 mg/m2 cisplatin weekly for a total of 7 weeks.

Intervention type

Drug

Phase

Phase II

Drug names

Cetuximab

Primary outcome measures

Objective response rate (ORR) of induction chemotherapy is measured by MRI according to RECIST criteria in week 7, after two cycles of C-TPF treatment.

Secondary outcome measures

1. Progression free survival will be measured by MRI first 2 months after bio-CRT and then every 3 months, until disease progression or patient death
2. Overall survival will be followed up until patient death at physicians' clinic visits every month
3. Efficacy of bio-CRT will be measure by comparing the first MRI 2 months after bio-CRT to the MRI taken after induction chemotherapy
4. Acute side effects are recorded during the treatment of induction and bio-CRT. Late side effects are recorded by physicians during the follow-up clinic visits.

Overall trial start date

05/07/2015

Overall trial end date

05/07/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged between 18-70 years
2. Histologically proven locally advanced inoperable stage IV oral squamous cell carcinoma (OSCC)
3. At least one measurable lesion
4. An ECOG performance status < 2
5. Adequate hematological profile (WBC > 3 x 109/L, neutrophils > 1.5 x109/L, hemoglobin > 9 g/dl, platelets > 100 x 109/L)
6. Adequate liver and renal function panel (serum bilirubin < 1.5 x ULN, AST/ALT < 5 x ULN, creatinine < 1.25 x ULN and/or creatinine clearance > 50 ml/min)
7. Life expectancy of more than 12 weeks
8. Effective contraception for both male and female subjects if the risk of conception exists

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

43

Participant exclusion criteria

1. Distant metastasis or locally recurrent tumors
2. Prior chemotherapy, radiotherapy or surgery for HNC
3. Simultaneous double cancers except for cervical carcinoma in situ
4. Localized skin squamous cell cancer, or basal cell carcinoma of the skin
5. Use of an investigational agent within the past 28 days prior to enrollment
6. Known grade 3/4 allergic reactions to any components of the treatment
7. Pregnancy or breast-feeding
8. Clinically active disease unrelated to cancer itself
9. History of severe pulmonary or cardiac disease in the past 12 months
10. Uncontrolled chronic neuropathy
11. Participation in another clinical trial within the past 30 days
12. Legal incapacity or limited legal capacity

Recruitment start date

30/09/2015

Recruitment end date

05/06/2018

Locations

Countries of recruitment

Taiwan

Trial participating centre

Taipei Veterans General Hospital
No. 201 Sec. 2 Shih-Pai Road
Taipei city
102
Taiwan

Sponsor information

Organisation

Taipei Veterans General Hospital

Sponsor details

No. 201
Sec. 2
Shih-Pai Rd.
Taipei 112
Taipei City
112
Taiwan

Sponsor type

Industry

Website

Funders

Funder type

Research organisation

Funder name

Taiwan Clinical Oncology Research Foundation

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Taipei Veterans General Hospital

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Ministry of Health and Welfare

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The initial result has been e-published on ASCO2015 poster (No. e17016). The final results will be submitted to a peer reviewed journal for publication.

Intention to publish date

31/12/2018

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes