Clinical Trials /

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

NCT00573989

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: IRB00003457
  • SECONDARY ID: P30CA012197
  • SECONDARY ID: CCCWFU-60107
  • NCT ID: NCT00573989
  • NCT ALIAS: NCT01580449

Conditions

  • Head and Neck Cancer

Interventions

DrugSynonymsArms
erlotinib hydrochlorideErlotinib
pemetrexed disodiumErlotinib

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
ErlotinibExperimentalErlotinib
  • erlotinib hydrochloride
  • pemetrexed disodium

Eligibility 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
      
Maximum Eligible Age:120 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose of Erlotinib Hydrochloride (Phase I)
Time Frame:56 Days
Safety Issue:
Description:Dose at which 100% of participants tolerated the dose

Secondary Outcome Measures

Measure:Median Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:Median Progression Free Survival of participants reported after 2 years.
Measure:Median Overall Survival
Time Frame:up to 5 years
Safety Issue:
Description:Median Overall Survival of participants reported after 2 years.
Measure:Overall Survival
Time Frame:1 and 2 years
Safety Issue:
Description:Overall survival of participants reported after 2 years.
Measure:Evaluation of Acute and Chronic Toxicity
Time Frame:1 year
Safety Issue:
Description:Evaluate acute and chronic toxicity of the combined re-irradiation with radiosensitizing drugs: Pemetrexed and Erlotinib. Adverse events with Common Toxicity Criteria grades of 4 and 5 are reported for phase I and II.
Measure:Change in Quality of Life- FACT H&N
Time Frame:baseline and 12 months
Safety Issue:
Description:The Functional Assessment of Cancer Therapy-Head and Neck (FACT H&N) consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for head and neck related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain. Score range is 0-156. Higher scores denotes better outcomes
Measure:Change in Quality of Life: PSS-HN
Time Frame:baseline and 6 months
Safety Issue:
Description:The Performance Status Scale for Head & Neck Cancer Patients (PSS-HN) is s designed to evaluate performance in areas of functioning most likely affected by head and neck cancer and its treatment, specifically Normalcy of Diet, Eating in Public, and Understandability of Speech. Each subscale is rated from 0 to 100, with higher scores indicating better performance
Measure:Change in Quality of Life: MDADI
Time Frame:baseline and 12 months
Safety Issue:
Description:The M.D. Anderson Dysphagia Inventory (MDADI) was used to assess effects of dysphagia on the quality of life of patients with head and neck cancer. It incorporates 3 domains (emotional, functional, and physical) as well as 1 global question. Each subscale with five possible responses scored on a scale of 1 to 5 (strongly agree, agree, no opinion, disagree and strongly disagree). Scores range from 0 (extremely low functioning) to 100 (higher functioning). Higher MDADI score represents better day-to-day functioning and better quality of life.
Measure:Evaluation of Biomarkers
Time Frame:throughout study completion, up to 2 years
Safety Issue:
Description:
Measure:Objective Tumor Response
Time Frame:1 year
Safety Issue:
Description:Objective Tumor Response reported on participants at 1 year (complete, partial, progression, or stable response).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Wake Forest University Health Sciences

Trial Keywords

  • 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

Last Updated

December 13, 2018