Back to results

Docetaxel, Cisplatin, and Fluorouracil Followed By Cetuximab and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer

Primary Purpose

Head and Neck Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

cetuximab

cisplatin

docetaxel

fluorouracil

computed tomography

positron emission tomography

quality-of-life assessment

3-dimensional conformal radiation therapy

intensity-modulated radiation therapy

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III verrucous carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage IV verrucous carcinoma of the larynx

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion:

Histologically confirmed (from primary lesion and/or lymph nodes) squamous cell carcinoma (SCC) of the head and neck, including the following subtypes:
- Oropharynx
- Hypopharynx
- Larynx
Primary site of tumor must not include any of the following:
- Nasopharynx
- Sinuses
- Salivary glands
Stage III or IV disease that is unresectable (oropharynx, larynx, or hypopharynx) OR that is resectable with organ-sparing goal (oropharynx or hypopharynx)
Measurable disease by CT scan or MRI
No definitive evidence of distant metastasis
ECOG performance status 0-1
ANC ≥ 1,500/μL
Platelet count ≥ 100,000/μL
Hemoglobin ≥ 8 g/dL
Total bilirubin ≤ normal
- Except in the case where the elevated total bilirubin is not a sign of liver disease (i.e., Gilbert syndrome), in which case a total bilirubin ≤ 2 times upper limit of normal (ULN) is allowed provided direct bilirubin is ≤ ULN
AST, ALT, and alkaline phosphate (AP) meeting the following criteria:
- AP normal AND AST or ALT ≤ 5 times upper limit of normal (ULN)
- AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
- AP ≤ 5 times ULN AND AST or ALT normal
Creatinine ≤ 1.5 mg/dL
Negative pregnancy test (for women of childbearing potential)
Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
Willing to undergo laryngoscopy with biopsy of residual tumor at primary site (as part of a comprehensive evaluation of tumor response after completion of the induction chemotherapy portion of study treatment)

Exclusion:

History of severe hypersensitivity reaction to docetaxel or to other drugs formulated with polysorbate 80
Other invasive malignancy within the past 3 years, except nonmelanoma skin cancer
Prior allergic reaction to the study drug(s)
Concurrent uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Psychiatric illness/social situation that would limit compliance with study requirements
- Significant history of uncontrolled cardiac disease, including any of the following:
  - Uncontrolled hypertension
  - Unstable angina
  - Myocardial infarction within the past 6 months
  - Uncontrolled congestive heart failure
  - Cardiomyopathy with decreased left ventricular ejection fraction (i.e., LVEF < 45%)
Uncontrolled condition that, in the opinion of the investigator, would interfere in the safe and timely completion of study procedures
History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on screening chest CT scan
HIV positivity
Pregnant or nursing
Prior chemotherapy for the study cancer
Prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
Prior chemotherapy, biological therapy, or hormone therapy within the last one year
Prior initial surgical treatment, except diagnostic biopsy of the primary site or nodal sampling of neck disease
Prior radical or modified neck dissection
Prior therapy that specifically and directly targets the EGFR pathway
Concurrent investigational agents

Sites / Locations

Wake Forest University Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TPFChemotherapy + Concomitant Cetuximab & RT

Arm Description

Taxotere/Cisplatinum/5-Fluorouracil (TPF) Chemotherapy Followed by Concomitant Cetuximab & Radiation Therapy

Outcomes

Primary Outcome Measures

Progression-free Survival

Secondary Outcome Measures

Objective Response Rate

Will be measured by CT scan /MRI of the head and neck with corroborative results of direct biopsy of any residual tumor at primary site.

Best Overall Response Rate

Defined as rate of complete and partial responses (at least 30% decrease in the sum of the longest diameter of target lesions), measured by CT scan or MRI of the head and neck after completion of multimodality treatment with induction TPF (Docetaxel, cisplatin and fluorouracil) chemotherapy followed by combined ERT. We will use RECIST (Response Evaluation Criteria In Solid Tumors) (Therasse et al, 2000) for evaluation of response.

Overall Survival

Number of Participants With Distant Metastasis

Quality of Life - Functional Assessment of Cancer Therapy - General (FACT-G)

Four subscales: physical well-being (PWB; 7-items, score range 0-28), social/family well-being (SWB; 7-items, score range 0-28), emotional well-being (EWB; 6-items, score range 0-24), and functional well-being (FWB; 7-items, score range 0-28). Items are rated on a five-point scale: 0-"not at all", 1- "a little bit", 2-"somewhat", 3- "quite a bit" and 4-"very much". Overall quality of life is the sum of the core items of the FACT-G possible range of 0-108 points. The higher the score the better the quality life. This interval includes 0, we will conclude that there is not conclusive statistical evidence that there is an improvement or worsening. If the interval does not include 0 we can determine whether there was a significant improvement (or worsening) depending on which side of the 0 the interval is on. The total outcome index score (possible range 0-108 points) is the sum of the physical and functional well being and additional concerns categories from the FACT-G.

Number of Participants With Local-Regional Control

Performance Status Scale for Head and Neck Cancer

Consists of assessment of three functions (subscales): Normalcy of diet, eating in public, and understandability of speech. The interviewer rates the patient on each scale based on the patient's responses to targeted questions. Scores range from 0-100 (Full performance (100 score), moderate or severe impairment (≤ 50 score)). The higher the score, the better the ability of the patient to function.

MD Anderson Dysphagia Inventory

The MD Anderson Dysphasia Inventory (MDADI) is a survey specifically designed to assess dysphasia. It contains 20 questions directly addressing the swallowing function and several other general questions. The questionnaire asks for participants views about their swallowing ability at baseline, pre-radiation therapy and post-radiation therapy. All questions except for E7 and F2: Strongly Agree = 1 point, Agree = 2 points, No Opinion = 3 points, Disagree = 4 points, Strongly Disagree. E7 and F2: Strongly agree = 5 points, Agree = 4 points, no opinion = 3 points, disagree = 2 points, strongly disagree = 1 point. Scores range from 20 (extremely low-functioning) to 100 (high-functioning).

Full Information

NCT ID

NCT00721513

First Posted

July 23, 2008

Last Updated

March 30, 2020

Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00721513

Brief Title

Docetaxel, Cisplatin, and Fluorouracil Followed By Cetuximab and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer

Official Title

Phase II Study to Evaluate the Efficacy and Toxicity of Multimodality Treatment With Induction Taxotere/Cisplatin?5-FU (TPF) Chemotherapy Followed by Concomitant Cetuximab and Radiation Therapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

September 2008 (undefined)

Primary Completion Date

August 2014 (Actual)

Study Completion Date

August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with cetuximab and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving docetaxel, cisplatin, and fluorouracil together with cetuximab and radiation therapy works in treating patients with locally advanced head and neck cancer.

Detailed Description

OBJECTIVES: Primary Evaluate the progression-free survival of patients with locally advanced squamous cell carcinoma of the head and neck treated with induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil followed by concurrent cetuximab and radiotherapy. Secondary Assess the objective response rate in patients treated with this regimen. Assess the best overall response rate, overall survival, local-regional control, and distant failure in patients treated with this regimen. Assess the acute and long-term toxicity associated with this regimen in these patients. Assess quality of life and swallowing in patients treated with this regimen. Determine the accuracy of PET/CT scan in evaluating objective response; in detecting residual disease at primary sites and nodes; in guiding the recommendation for salvage surgery or for neck dissection; and in early detection of recurrent or metastatic disease. OUTLINE: Patients are stratified according to nodal status (N2b-c or N3 vs N0-2a), tumor characteristics of invasiveness (present vs absent), human papilloma virus (HPV) status (positive vs negative), and primary tumor site (hypopharynx vs larynx vs oropharynx). Patients receive induction chemotherapy comprising docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1 and fluorouracil IV continuously on days 1-4. Treatment repeats every 3 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-4 weeks after completion of induction chemotherapy, patients receive cetuximab IV once weekly for 7 weeks. Beginning 1 week after the first dose of cetuximab, patients undergo concurrent intensity-modulated radiotherapy or conventional 3-dimensional radiotherapy once or twice daily 5-6 days a week for up to 6 weeks. Patients with persistent disease undergo salvage resection of the primary tumor and/or neck dissection approximately 3 months after the completion of radiotherapy. Patients undergo quality of life and swallowing evaluations periodically. Patients undergo PET/CT scan at baseline, before beginning radiotherapy, at 6-8 weeks after completion of study treatment, every 6 months for 5 years, and then annually thereafter. After completion of study treatment, patients are followed at 4 and 8 weeks, every 2 months for 2 years, every 3 months for 1 year, and then every 6 months thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Head and Neck Cancer

Keywords

stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III verrucous carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage IV verrucous carcinoma of the larynx

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

TPFChemotherapy + Concomitant Cetuximab & RT

Arm Type

Experimental

Arm Description

Taxotere/Cisplatinum/5-Fluorouracil (TPF) Chemotherapy Followed by Concomitant Cetuximab & Radiation Therapy

Intervention Type

Biological

Intervention Name(s)

cetuximab

Intervention Type

Drug

Intervention Name(s)

cisplatin

Intervention Type

Drug

Intervention Name(s)

docetaxel

Intervention Type

Drug

Intervention Name(s)

fluorouracil

Intervention Type

Procedure

Intervention Name(s)

computed tomography

Intervention Type

Procedure

Intervention Name(s)

positron emission tomography

Intervention Type

Procedure

Intervention Name(s)

quality-of-life assessment

Intervention Type

Radiation

Intervention Name(s)

3-dimensional conformal radiation therapy

Intervention Type

Radiation

Intervention Name(s)

intensity-modulated radiation therapy

Primary Outcome Measure Information:

Title

Progression-free Survival

Time Frame

up to 2 years

Secondary Outcome Measure Information:

Title

Objective Response Rate

Description

Will be measured by CT scan /MRI of the head and neck with corroborative results of direct biopsy of any residual tumor at primary site.

Time Frame

up to 2 years

Title

Best Overall Response Rate

Description

Time Frame

up to 2 years

Title

Overall Survival

Time Frame

up to 2 years

Title

Number of Participants With Distant Metastasis

Time Frame

up to 2 years

Title

Quality of Life - Functional Assessment of Cancer Therapy - General (FACT-G)

Description

Time Frame

Baseline, pre-radiation therapy and post-radiation therapy, up to 2 years

Title

Number of Participants With Local-Regional Control

Time Frame

up to 2 years

Title

Performance Status Scale for Head and Neck Cancer

Description

Time Frame

Baseline, pre-radiation therapy and post-radiation therapy, up to 2 years

Title

MD Anderson Dysphagia Inventory

Description

Time Frame

Baseline, pre-radiation therapy and post-radiation therapy, up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion: Histologically confirmed (from primary lesion and/or lymph nodes) squamous cell carcinoma (SCC) of the head and neck, including the following subtypes: Oropharynx Hypopharynx Larynx Primary site of tumor must not include any of the following: Nasopharynx Sinuses Salivary glands Stage III or IV disease that is unresectable (oropharynx, larynx, or hypopharynx) OR that is resectable with organ-sparing goal (oropharynx or hypopharynx) Measurable disease by CT scan or MRI No definitive evidence of distant metastasis ECOG performance status 0-1 ANC ≥ 1,500/μL Platelet count ≥ 100,000/μL Hemoglobin ≥ 8 g/dL Total bilirubin ≤ normal Except in the case where the elevated total bilirubin is not a sign of liver disease (i.e., Gilbert syndrome), in which case a total bilirubin ≤ 2 times upper limit of normal (ULN) is allowed provided direct bilirubin is ≤ ULN AST, ALT, and alkaline phosphate (AP) meeting the following criteria: AP normal AND AST or ALT ≤ 5 times upper limit of normal (ULN) AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN AP ≤ 5 times ULN AND AST or ALT normal Creatinine ≤ 1.5 mg/dL Negative pregnancy test (for women of childbearing potential) Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment Willing to undergo laryngoscopy with biopsy of residual tumor at primary site (as part of a comprehensive evaluation of tumor response after completion of the induction chemotherapy portion of study treatment) Exclusion: History of severe hypersensitivity reaction to docetaxel or to other drugs formulated with polysorbate 80 Other invasive malignancy within the past 3 years, except nonmelanoma skin cancer Prior allergic reaction to the study drug(s) Concurrent uncontrolled illness including, but not limited to, any of the following: Ongoing or active infection Psychiatric illness/social situation that would limit compliance with study requirements Significant history of uncontrolled cardiac disease, including any of the following: Uncontrolled hypertension Unstable angina Myocardial infarction within the past 6 months Uncontrolled congestive heart failure Cardiomyopathy with decreased left ventricular ejection fraction (i.e., LVEF < 45%) Uncontrolled condition that, in the opinion of the investigator, would interfere in the safe and timely completion of study procedures History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on screening chest CT scan HIV positivity Pregnant or nursing Prior chemotherapy for the study cancer Prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields Prior chemotherapy, biological therapy, or hormone therapy within the last one year Prior initial surgical treatment, except diagnostic biopsy of the primary site or nodal sampling of neck disease Prior radical or modified neck dissection Prior therapy that specifically and directly targets the EGFR pathway Concurrent investigational agents

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mercedes Porosnicu, MD

Organizational Affiliation

Wake Forest University Health Sciences

Official's Role

Principal Investigator

Facility Information:

Facility Name

Wake Forest University Comprehensive Cancer Center

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157-1096

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Docetaxel, Cisplatin, and Fluorouracil Followed By Cetuximab and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer

We'll reach out to this number within 24 hrs