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Cetuximab, Carboplatin, and Paclitaxel Followed by Radiation Therapy, With or Without Cisplatin, in Treating Patients With Metastatic Head and Neck Cancer

Primary Purpose

Head and Neck Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cetuximab
Carboplatin
Paclitaxel
Conventional Surgery
Radiation Therapy
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

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

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients with histological proof (from the primary lesion and/or lymph nodes) of squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx. Patients should have stage IV disease, stage T0-4 N2b/2c/3 M0 (for nasopharynx patients, stage N1 disease is eligible). Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) is required. Patients with stage Tx primary disease are eligible if there is N2b/3 adenopathy. Karnofsky performance status of >/= 80 or Eastern Cooperative Oncology Group (ECOG) point scale 0-1 Age > 16 years Patients should have adequate bone marrow function defined as an absolute peripheral granulocyte count (AGC) of > 1500 cells/mm3 and platelet count of > 100,000 cells/mm3; adequate hepatic function with bilirubin </= Upper Limit of Normal (ULN), aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) may be up to 2.5 times the upper limit of normal if alkaline phosphatase is normal. Alkaline phosphatase may be up to 4* ULN if SGPT and SGOT are normal. Patients who have both SGPT and SGOT > 1.5 ULN and alkaline phosphatase > 2.5 * ULN are not eligible. Normal PT/PTT and normal serum calcium (without intervention) are required. Creatinine clearance > 40 ml/min determined by 24 hour collection or nomogram: CrCl male = (140 - age) times (weight in kg)/serum Cr times 72 CrCl female = 0.85 times (CrCl male) Patients should have no serious acute or chronic co-morbid condition, or acute infection. Patients must sign a study-specific informed consent form. Exclusion Criteria: Histology other than squamous cell carcinoma. Evidence of distant metastases (below the clavicle) by clinical or radiographic means. Karnofsky performance status < 80 or ECOG>1 Prior chemotherapy, within the previous 3 years. Prior radiotherapy to the head and neck. Prior cetuximab therapy, prior therapy with any other drug that targets the EGFR pathway, or prior therapy with a murine or chimeric monoclonal antibody. Initial surgical resection rendering the patient clinically and radiologically disease free. Simultaneous primary invasive cancers. Patients with another malignancy (excluding non melanoma skin cancers, and cancers treated > 3 years prior for which patient remains continuously disease free). Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the study. Subjects who are men must also agree to use effective contraception. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG)) within 72 hours prior to the start of study medication. WOCBP using a prohibited contraceptive method. Women who are pregnant or breastfeeding. Women with a positive pregnancy test on enrollment or prior to study drug administration. Refusal to sign the informed consent. Pre-existing peripheral neuropathy Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or worse.

Sites / Locations

  • M.D. Anderson Cancer Center at University of Texas

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cetuximab + Carboplatin/Paclitaxel

Arm Description

Cetuximab beginning weekly dose 400 mg/m^2 intravenous (IV), and 250 mg/m^2 weeks 2-6; Weekly Carboplatin area under the curve (AUC) 2 and Paclitaxel 135 mg/m^2 for 6 courses.

Outcomes

Primary Outcome Measures

Number of Participants With Complete Response
Number of participants with a complete response. Complete Response (CR): Disappearance of clinical and radiological evidence of tumor.

Secondary Outcome Measures

Full Information

First Posted
March 8, 2006
Last Updated
February 26, 2013
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00301028
Brief Title
Cetuximab, Carboplatin, and Paclitaxel Followed by Radiation Therapy, With or Without Cisplatin, in Treating Patients With Metastatic Head and Neck Cancer
Official Title
Phase II Trial of Induction Therapy With Cetuximab (C225) and Carboplatin/Paclitaxel Chemotherapy in Previously Untreated Patients With Advanced (Stage IV) Head & Neck Squamous Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
April 2006 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin, paclitaxel, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. Giving cetuximab together with combination chemotherapy and radiation therapy, with or without cisplatin, may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cetuximab together with carboplatin and paclitaxel followed by radiation therapy, with or without cisplatin, works in treating patients with metastatic head and neck cancer.
Detailed Description
OBJECTIVES: Primary Determine the increase in clinical/radiographic complete response rate in patients with previously untreated metastatic squamous cell carcinoma of the head and neck treated with induction therapy comprising cetuximab, carboplatin, and paclitaxel. Determine the toxic effects of this regimen in these patients. Secondary Determine the pattern of tumor recurrence in patients treated with this regimen. Determine the quality of life of patients treated with this regimen. Determine the duration of response, time to progression, and survival of patients treated with this regimen. Correlate effects of this regimen with biomarkers of response and predictors of long-term outcome in these patients. OUTLINE: This is a nonrandomized, open-label study. Patients receive induction therapy comprising cetuximab IV over 1-2 hours, paclitaxel IV over 1 hour, and carboplatin IV over 1 hour on day 1. Treatment repeats weekly for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-3 weeks later, patients undergo radiotherapy or chemoradiotherapy. Patients with T0, 1, 2 disease undergo radiotherapy 5 days a week for 6 weeks. Patients with T3, 4 disease or unresectable nodal disease undergo radiotherapy 5 days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours on days 1 and 22. Some patients may undergo primary surgical resection before or instead of radiotherapy or chemoradiotherapy. Quality of life is assessed at baseline and at 6, 12, and 24 months after completion of radiotherapy or surgery. After study completion, patients are followed every 3 months for 2 years, every 4 months for 1 year, and every 6 months for 2 years. PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

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 IV squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the lip and oral cavity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cetuximab + Carboplatin/Paclitaxel
Arm Type
Experimental
Arm Description
Cetuximab beginning weekly dose 400 mg/m^2 intravenous (IV), and 250 mg/m^2 weeks 2-6; Weekly Carboplatin area under the curve (AUC) 2 and Paclitaxel 135 mg/m^2 for 6 courses.
Intervention Type
Biological
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
C225, Erbitux, IMC-C225
Intervention Description
Beginning weekly dose 400 mg/m^2 IV over 1-2 hours, and 250 mg/m^2 weeks 2-6.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Paraplatin
Intervention Description
AUC 2 weekly for 6 courses.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Taxol
Intervention Description
135 mg/m^2 weekly for 6 courses.
Intervention Type
Procedure
Intervention Name(s)
Conventional Surgery
Intervention Description
Following induction in second part of study.
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Other Intervention Name(s)
Radiotherapy, RT, XRT
Intervention Description
Following induction in second part of study.
Primary Outcome Measure Information:
Title
Number of Participants With Complete Response
Description
Number of participants with a complete response. Complete Response (CR): Disappearance of clinical and radiological evidence of tumor.
Time Frame
Study period of 3 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with histological proof (from the primary lesion and/or lymph nodes) of squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx. Patients should have stage IV disease, stage T0-4 N2b/2c/3 M0 (for nasopharynx patients, stage N1 disease is eligible). Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) is required. Patients with stage Tx primary disease are eligible if there is N2b/3 adenopathy. Karnofsky performance status of >/= 80 or Eastern Cooperative Oncology Group (ECOG) point scale 0-1 Age > 16 years Patients should have adequate bone marrow function defined as an absolute peripheral granulocyte count (AGC) of > 1500 cells/mm3 and platelet count of > 100,000 cells/mm3; adequate hepatic function with bilirubin </= Upper Limit of Normal (ULN), aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) may be up to 2.5 times the upper limit of normal if alkaline phosphatase is normal. Alkaline phosphatase may be up to 4* ULN if SGPT and SGOT are normal. Patients who have both SGPT and SGOT > 1.5 ULN and alkaline phosphatase > 2.5 * ULN are not eligible. Normal PT/PTT and normal serum calcium (without intervention) are required. Creatinine clearance > 40 ml/min determined by 24 hour collection or nomogram: CrCl male = (140 - age) times (weight in kg)/serum Cr times 72 CrCl female = 0.85 times (CrCl male) Patients should have no serious acute or chronic co-morbid condition, or acute infection. Patients must sign a study-specific informed consent form. Exclusion Criteria: Histology other than squamous cell carcinoma. Evidence of distant metastases (below the clavicle) by clinical or radiographic means. Karnofsky performance status < 80 or ECOG>1 Prior chemotherapy, within the previous 3 years. Prior radiotherapy to the head and neck. Prior cetuximab therapy, prior therapy with any other drug that targets the EGFR pathway, or prior therapy with a murine or chimeric monoclonal antibody. Initial surgical resection rendering the patient clinically and radiologically disease free. Simultaneous primary invasive cancers. Patients with another malignancy (excluding non melanoma skin cancers, and cancers treated > 3 years prior for which patient remains continuously disease free). Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the study. Subjects who are men must also agree to use effective contraception. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG)) within 72 hours prior to the start of study medication. WOCBP using a prohibited contraceptive method. Women who are pregnant or breastfeeding. Women with a positive pregnancy test on enrollment or prior to study drug administration. Refusal to sign the informed consent. Pre-existing peripheral neuropathy Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or worse.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Merrill S. Kies, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Vassiliki A. Papadimitrakopoulou, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M.D. Anderson Cancer Center at University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19917840
Citation
Kies MS, Holsinger FC, Lee JJ, William WN Jr, Glisson BS, Lin HY, Lewin JS, Ginsberg LE, Gillaspy KA, Massarelli E, Byers L, Lippman SM, Hong WK, El-Naggar AK, Garden AS, Papadimitrakopoulou V. Induction chemotherapy and cetuximab for locally advanced squamous cell carcinoma of the head and neck: results from a phase II prospective trial. J Clin Oncol. 2010 Jan 1;28(1):8-14. doi: 10.1200/JCO.2009.23.0425. Epub 2009 Nov 16.
Results Reference
result
PubMed Identifier
25057165
Citation
Psyrri A, Rampias T, Vermorken JB. The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck. Ann Oncol. 2014 Nov;25(11):2101-2115. doi: 10.1093/annonc/mdu265. Epub 2014 Jul 23.
Results Reference
derived
Links:
URL
http://www.mdanderson.org
Description
UT MD Anderson Cancer Center Website

Learn more about this trial

Cetuximab, Carboplatin, and Paclitaxel Followed by Radiation Therapy, With or Without Cisplatin, in Treating Patients With Metastatic Head and Neck Cancer

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