Intensity-Modulated Radiation Therapy, Pemetrexed, and Erlotinib in Treating Patients With Recurrent or Second Primary Head and Neck Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Comprehensive Cancer Center of Wake Forest University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier:
NCT00573989
First received: December 13, 2007
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs, such as pemetrexed and erlotinib, may make tumor cells more sensitive to radiation therapy. Erlotinib and pemetrexed may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving intensity-modulated radiation therapy together with pemetrexed and erlotinib may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with intensity-modulated radiation therapy and pemetrexed and to see how well they work in treating patients with recurrent or second primary head and neck cancer.


Condition Intervention Phase
Head and Neck Cancer
Drug: erlotinib hydrochloride
Drug: pemetrexed disodium
Procedure: quality-of-life assessment
Radiation: intensity-modulated radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I/II Clinical Trial of Combined Pre-Irradiation With Pemetrexed and Erlotinib Followed by Maintenance Erlotinib for Recurrent and Second Primary Squamous Cell Carcinoma of the Head and Neck

Resource links provided by NLM:


Further study details as provided by Comprehensive Cancer Center of Wake Forest University:

Primary Outcome Measures:
  • Maximum tolerated dose of erlotinib hydrochloride (Phase I) [ Designated as safety issue: Yes ]
  • Progression-free survival (PFS) at 1 year (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Median PFS, median overall survival (OS), and OS at 1 and 2 years [ Designated as safety issue: No ]
  • Objective tumor response as measured by CT scan or MRI [ Designated as safety issue: No ]
  • Toxicity and tolerability [ Designated as safety issue: Yes ]
  • Quality of life as measured by speech and swallowing studies and nutrition and pain evaluations [ Designated as safety issue: No ]
  • Biomarker predictor of response and tissue prognostic markers [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: March 2008
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Evaluate the acute toxicity and feasibility of intensity modulated radiotherapy (IMRT) in combination with radiosensitizing drugs pemetrexed disodium and erlotinib hydrochloride in patients with recurrent or second primary squamous cell carcinoma of the head and neck. (Phase I)
  • Determine the maximum tolerated dose and recommended phase II dose of erlotinib hydrochloride in these patients. (Phase I)
  • Determine progression-free survival (PFS) at 1 year in these patients. (Phase II)

Secondary

  • Determine median PFS, median overall survival (OS), and OS at 1 and 2 years in these patients.
  • Determine objective tumor response as measured by CT scan or MRI in these patients.
  • Evaluate the acute and chronic toxicity of IMRT in combination with radiosensitizing drugs pemetrexed disodium and erlotinib hydrochloride in these patients.
  • Evaluate the impact of treatment on quality of life as measured by FACT-H&N, PSS-HN, MD Anderson Dysphagia Inventory (MDADI), and swallowing by direct functional measurements at different time points.
  • Evaluate the level of phosphorylation of different tyrosine residues within the cytoplasmic domain of EGFR, bound adaptors, as well as markers of downstream pathways activation by nano LC-MS/MS in tumor tissue and correlate with levels of P-AKT and P-ERK by immunohistochemistry and with response to treatment.
  • Measure the levels of TS and p53 and correlate with treatment response.

OUTLINE: This is a phase I, dose-escalation study of erlotinib hydrochloride followed by a phase II study.

  • Phase I: Patients undergo intensity modulated radiotherapy (IMRT) once daily, 5 days a week, for 6 weeks. Patients receive pemetrexed disodium IV over 10 minutes on day 1 of radiotherapy. Treatment with pemetrexed disodium repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral erlotinib hydrochloride once daily beginning on day 1 of radiotherapy and continuing for up to 2 years in the absence of disease progression or unacceptable toxicity.
  • Phase II: Patients undergo IMRT and receive pemetrexed sodium as in phase I. Patients also receive erlotinib hydrochloride at the maximum tolerated dose determined in phase I.

Quality of life is assessed at baseline, weekly during treatment, at 1, 6, and 12 months, and then annually thereafter.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 1 year, and then annually thereafter.

  Eligibility

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

Inclusion:

* Histologically or cytologically confirmed diagnosis of recurrent or second primary squamous cell carcinoma (SCC) of the head and neck, including any of the following:

  • Oral cavity
  • Oropharynx
  • Hypopharynx
  • Larynx
  • Recurrent neck metastases with unknown primary

Exception from pathology confirmation of tumor recurrence is accepted for patients who originally had pathologically confirmed SCC of the Head and Neck, the new tumor is located in the head and neck area and it is clinically considered as a recurrence of the original tumor, and a tumor biopsy is technically difficult and would expose the patient to unjustified risk. The treating physicians should agree and document the clinical definition of tumor recurrence and should document the increased risk for biopsy.

  • Measurable disease by CT scan or MRI OR evaluable disease
  • No definitive evidence of distant metastasis
  • Unresectable disease by a preliminary ENT evaluation OR refused surgery
  • Patients may have received chemotherapy as a component of their primary tumor treatment but not for recurrent or metastatic disease. No prior treatment with systemic anti-EGFR inhibitors or Pemetrexed is permitted
  • Has undergone prior head and neck radiotherapy (for SCC of the head and neck) to a dose of ≤ 72 Gy that involved most of the recurrent tumor (> 75%) OR has a second primary tumor volume in areas previously irradiated to > 45 Gy
  • The entire tumor volume must be included in a treatment field that limits the total spinal cord dose to 54 Gy (prior plus planned dose)
  • Must have disease recurrence or persistence for ≥ 6 months after completion of prior radiotherapy
  • ECOG performance status 0-1
  • Age ≥ 18 years
  • ANC > 1,500/µL
  • Platelet count > 100,000/µL
  • Total bilirubin < 1.5 times upper limit of normal (ULN)
  • AST/ALT < 2 times ULN
  • Creatinine < 1.5 times ULN
  • Willing and able to take folic acid and vitamin B12 supplementation
  • Recovered from prior surgery, chemotherapy, or radiotherapy
  • At least 6 months since prior radiotherapy
  • At least 5 days since prior aspirin or other non-steroidal anti-inflammatory agents (8 days for long acting agents [e.g., piroxicam])
  • Fertile patients must use effective contraception

Exclusion:

  • Nasopharyngeal carcinoma
  • Concurrent uncontrolled illness, including, but not limited to, any of the following:

    • Ongoing or active infection
    • Psychiatric illness or social situation that would limit compliance with study requirements
    • Significant history of uncontrolled cardiac disease (i.e., uncontrolled hypertension; unstable angina; recent myocardial infarction [within the past 3 months]; uncontrolled congestive heart failure; or cardiomyopathy with decreased ejection fraction)
  • Active interstitial lung disease
  • Presence of third space fluid that cannot be controlled by drainage
  • Other concurrent investigational agents
  • Pregnant or nursing
  • HIV positive
  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: NCT00573989

Locations
United States, North Carolina
UNC Linberger Comprehensive Cancer Center Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Dale Flowers, OCN    919-843-9357    dale_flowers@med.unc.edu   
Wake Forest University Comprehensive Cancer Center Recruiting
Winston-Salem, North Carolina, United States, 27157-1096
Contact: Clinical Trials Office - Wake Forest University Comprehensive    336-713-6771      
Sponsors and Collaborators
Comprehensive Cancer Center of Wake Forest University
Investigators
Principal Investigator: Mercedes Porosnicu, MD Comprehensive Cancer Center of Wake Forest University
Principal Investigator: Kathryn M. Greven, MD Comprehensive Cancer Center of Wake Forest University
  More Information

Additional Information:
No publications provided

Responsible Party: Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier: NCT00573989     History of Changes
Obsolete Identifiers: NCT01580449
Other Study ID Numbers: CDR0000578838, P30CA012197, CCCWFU-60107, LILLY-CCCWFU-60107, CCCWFU-IRB00003457
Study First Received: December 13, 2007
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Comprehensive Cancer Center of Wake Forest University:
recurrent squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
recurrent verrucous carcinoma of the larynx
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent verrucous carcinoma of the oral cavity
metastatic squamous neck cancer with occult primary squamous cell carcinoma
recurrent metastatic squamous neck cancer with occult primary
recurrent squamous cell carcinoma of the oropharynx

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
Pemetrexed
Erlotinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 28, 2014