Carboplatin, Paclitaxel, Cetuximab, and Erlotinib Hydrochloride in Treating Patients With Metastatic or Recurrent Head and Neck Squamous Cell Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Fox Chase Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fox Chase Cancer Center
ClinicalTrials.gov Identifier:
NCT01316757
First received: March 8, 2011
Last updated: June 11, 2014
Last verified: June 2014
  Purpose

This phase II trial is studying how well giving carboplatin, paclitaxel, cetuximab, and erlotinib hydrochloride together works in treating patients with metastatic or recurrent squamous cell head and neck cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with cetuximab and erlotinib hydrochloride may kill more tumor cells.


Condition Intervention Phase
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
Recurrent Metastatic Squamous Neck Cancer With Occult Primary
Recurrent Salivary Gland Cancer
Recurrent Squamous Cell Carcinoma of the Hypopharynx
Recurrent Squamous Cell Carcinoma of the Larynx
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Nasopharynx
Recurrent Squamous Cell Carcinoma of the Oropharynx
Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Recurrent Verrucous Carcinoma of the Larynx
Recurrent Verrucous Carcinoma of the Oral Cavity
Salivary Gland Squamous Cell Carcinoma
Stage IV Salivary Gland Cancer
Stage IV Squamous Cell Carcinoma of the Hypopharynx
Stage IV Squamous Cell Carcinoma of the Larynx
Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Stage IV Squamous Cell Carcinoma of the Oropharynx
Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IV Verrucous Carcinoma of the Larynx
Stage IV Verrucous Carcinoma of the Oral Cavity
Tongue Cancer
Untreated Metastatic Squamous Neck Cancer With Occult Primary
Biological: cetuximab
Drug: paclitaxel
Drug: carboplatin
Drug: erlotinib hydrochloride
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Carboplatin/Paclitaxel and Cetuximab, Followed by Carboplatin/Paclitaxel/Cetuximab and Erlotinib, With Correlative Studies in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck.

Resource links provided by NLM:


Further study details as provided by Fox Chase Cancer Center:

Primary Outcome Measures:
  • Objective response rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Complete plus partial response as determined by RECIST v 1.1


Secondary Outcome Measures:
  • Toxicity of study treatment [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]
    Assessed by National Cancer Institute (NCI) Common Toxicity Criteria (CTCAE) v.4.0. Proportions and 95% confidence intervals will be used.

  • Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Will use Kaplan-Meier curves.

  • EGFR assay levels [ Time Frame: Between courses 1 and 2 ] [ Designated as safety issue: No ]
    Will use a Wilcoxon paired-sample test.

  • Response rates [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Proportions and 95% confidence intervals

  • Biomarkers related to EGFR [ Time Frame: Between courses 1 and 2 ] [ Designated as safety issue: No ]
    Will use Spearman correlations to assess the associations of the biomarkers with each other.


Estimated Enrollment: 43
Study Start Date: February 2011
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, monoclonal antibody, enzyme inhibitor
Patients receive cetuximab IV over 60 minutes, paclitaxel IV over 1 hour, and carboplatin IV over 30 minutes on day 1. Beginning in course 2, patients also receive erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the objective response rate when erlotinib is added to combination carboplatin/paclitaxel/cetuximab systemic therapy in metastatic/recurrent head and neck cancer.

SECONDARY OBJECTIVES:

I. Secondary endpoints will be toxicity, overall survival, and laboratory correlates to determine if epidermal growth factor receptor (EGFR) signaling is more effectively inhibited after the addition of erlotinib than it is after chemotherapy/cetuximab without erlotinib.

OUTLINE:

Patients receive cetuximab intravenously (IV) over 60 minutes, paclitaxel IV over 1 hour, and carboplatin IV over 30 minutes on day 1. Beginning in course 2, patients also receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Criteria:

  • Histologically confirmed squamous cell carcinoma of the head and neck that is metastatic or recurrent
  • No prior systemic therapy for metastatic/recurrent disease
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Prior chemotherapy in the induction, organ preservation or adjuvant setting is permitted if it was completed more than 4 months prior to enrollment on the current study
  • Prior cetuximab is permitted if it was given for no more than 9 doses in combination with radiation therapy or chemoradiation therapy for initial treatment of locally advanced disease
  • No prior erlotinib, gefitinib or lapatinib therapy is permitted; nor is prior exposure to any investigational EGFR or panErbB reversible or irreversible inhibitor or any prior panitumumab or investigational EGFR-directed monoclonal antibody permitted
  • Hemoglobin > 9.0 G/dl
  • Absolute neutrophil count (ANC) > 1500 cells/mcl
  • Creatinine (Cr) < 1.8
  • Total bilirubin =< the institution's upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine transaminase (ALT) < 2 X ULN
  • No chronic active viral infection
  • No other malignancy within 3 years
  • No chronic diarrheal condition
  • Females should not be pregnant or breast feeding because chemotherapy may be harmful to the fetus or the nursing infant; also, the effects of erlotinib and cetuximab on the developing human fetus are unknown
  • All females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy
  • Women of childbearing potential and sexually active males must use an accepted and effective method of contraception while on treatment and for three months after the completion of treatment
  • Patients must have measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST); baseline measurements and evaluations must be obtained within < 4 weeks of randomization; all areas of disease should be recorded and mapped out in order to assess response and uniformity of response to therapy; disease in previously irradiated sites is considered measurable if there has been unequivocal disease progression or biopsy-proven residual carcinoma following radiation therapy; persistent disease without clear-cut progression after radiotherapy can be considered measurable if biopsy-proven at least 8 weeks after completion of radiation therapy
  • Patients with a prior history of squamous cell or basal carcinoma of the skin or in situ cervical cancer must have been curatively treated; patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 3 years post diagnosis
  • No current peripheral neuropathy > grade 2 at time of randomization
  • Patients must not have any co-existing condition that would preclude full compliance with the study
  • Human immunodeficiency virus (HIV) positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with erlotinib
  • Patients must have no history of allergic reaction to murine proteins
  • Ability to understand and the willingness to sign a written informed consent
  • Patients must not be receiving other investigational anti-cancer therapy
  • Patients with brain metastases are not eligible
  • Both men and women and members of all races and ethnic groups are eligible for this trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01316757

Locations
United States, New York
Univesity of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Contact: Mohamed Tejani, MD    585-275-5863    Mohamed_Tejani@urmc.rochester.edu   
Principal Investigator: Mohamed Tejani, MD         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111-2497
Contact: Renee Mehra, MD    215-728-3639    renee.mehra@fccc.edu   
Principal Investigator: Renee Mehra, MD         
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Isabel Villalobos, MS    214-648-7010    Isabel.Villalobos@utsouthwestern.edu   
Principal Investigator: Saad Khan, MD         
Sponsors and Collaborators
Fox Chase Cancer Center
Investigators
Principal Investigator: Renee Mehra, MD Fox Chase Cancer Center
  More Information

No publications provided

Responsible Party: Fox Chase Cancer Center
ClinicalTrials.gov Identifier: NCT01316757     History of Changes
Other Study ID Numbers: FER-HN-027, NCI-2011-00272, P30CA006927
Study First Received: March 8, 2011
Last Updated: June 11, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Nasopharyngeal Neoplasms
Paranasal Sinus Neoplasms
Salivary Gland Neoplasms
Head and Neck Neoplasms
Oropharyngeal Neoplasms
Carcinoma, Verrucous
Laryngeal Diseases
Laryngeal Neoplasms
Neoplasms, Unknown Primary
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Nose Neoplasms
Nose Diseases
Respiratory Tract Diseases
Paranasal Sinus Diseases
Respiratory Tract Neoplasms
Mouth Neoplasms
Mouth Diseases
Salivary Gland Diseases

ClinicalTrials.gov processed this record on September 16, 2014