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

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by (Responsible Party):	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00301028

Purpose

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.

Condition	Intervention	Phase
Head and Neck Cancer	Biological: Cetuximab Drug: Carboplatin Drug: Paclitaxel Procedure: Conventional Surgery Radiation: Radiation Therapy	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Head and Neck Cancer

Drug Information available for: Paclitaxel Carboplatin Cetuximab

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Complete Response Rate [ Time Frame: Study period of 3 Years ] [ Designated as safety issue: No ]
Percentage of patients with complete response. Complete Response (CR): Disappearance of clinical and radiological evidence of tumor.

Enrollment:	48
Study Start Date:	April 2006
Study Completion Date:	September 2011
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cetuximab + Carboplatin/Paclitaxel Cetuximab beginning weekly dose 400 mg/m^2 intravenous (IV), and 250 mg/m^2 weeks 2-6; Weekly Carboplatin AUC 2 and Paclitaxel 135 mg/m^2 for 6 courses.	Biological: Cetuximab Beginning weekly dose 400 mg/m^2 IV over 1-2 hours, and 250 mg/m^2 weeks 2-6. Other Names: C225 Erbitux IMC-C225 Drug: Carboplatin AUC 2 weekly for 6 courses. Other Name: Paraplatin Drug: Paclitaxel 135 mg/m^2 weekly for 6 courses. Other Name: Taxol Procedure: Conventional Surgery Following induction in second part of study. Radiation: Radiation Therapy Following induction in second part of study. Other Names: Radiotherapy RT XRT

Arms

Assigned Interventions

Experimental: Cetuximab + Carboplatin/Paclitaxel

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

Biological: Cetuximab

Beginning weekly dose 400 mg/m^2 IV over 1-2 hours, and 250 mg/m^2 weeks 2-6.

Other Names:

C225
Erbitux
IMC-C225

Drug: Carboplatin

AUC 2 weekly for 6 courses.

Other Name: Paraplatin

Drug: Paclitaxel

135 mg/m^2 weekly for 6 courses.

Other Name: Taxol

Procedure: Conventional Surgery

Following induction in second part of study.

Radiation: Radiation Therapy

Following induction in second part of study.

Other Names:

Radiotherapy
RT
XRT

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.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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 (wt 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 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 CTCAE grade 2 or worse.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00301028

Locations

United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:	Merrill S. Kies, MD	M.D. Anderson Cancer Center
Principal Investigator:	Vassiliki A. Papadimitrakopoulou, MD	M.D. Anderson Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

UT MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site

Publications:

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. Epub 2009 Nov 16.

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00301028 History of Changes
Other Study ID Numbers:	2003-0919, P50CA097007, P30CA016672, MDA-2003-0919, BMS-CA225054, CDR0000441273
Study First Received:	March 8, 2006
Last Updated:	September 19, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

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

Additional relevant MeSH terms:

Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cetuximab
Carboplatin

Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 21, 2012