Intensity-Modulated Radiation Therapy, Pemetrexed, and Erlotinib in Treating Patients With Recurrent or Second Primary Head and Neck Cancer
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|ClinicalTrials.gov Identifier: NCT00573989|
Recruitment Status : Terminated (Drug Supply Issue)
First Posted : December 14, 2007
Results First Posted : December 13, 2018
Last Update Posted : January 3, 2019
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 or disease||Intervention/treatment||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|
- 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)
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||March 2008|
|Actual Primary Completion Date :||March 2017|
|Actual Study Completion Date :||March 2017|
Drug: erlotinib hydrochloride
Drug: pemetrexed disodium
Procedure: quality-of-life assessment
Radiation: intensity-modulated radiation therapy
- Maximum Tolerated Dose of Erlotinib Hydrochloride (Phase I) [ Time Frame: 56 Days ]Dose at which 100% of participants tolerated the dose
- Progression-free Survival (PFS) at 1 Year (Phase II) [ Time Frame: 1 year ]Determine Progression Free Survival at 1 year defined as the percentage of patients who are alive at 1 year after beginning of their concurrent re-irradiation and chemotherapy without loco-regional progression of their disease as measured by CT scan or MRI.
- Median Progression Free Survival [ Time Frame: 2 years ]Median Progression Free Survival of participants reported after 2 years.
- Median Overall Survival [ Time Frame: up to 5 years ]Median Overall Survival of participants reported after 2 years.
- Overall Survival [ Time Frame: 1 and 2 years ]Overall survival of participants reported after 2 years.
- Evaluation of Acute and Chronic Toxicity [ Time Frame: 1 year ]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.
- Change in Quality of Life- FACT H&N [ Time Frame: baseline and 12 months ]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
- Change in Quality of Life: PSS-HN [ Time Frame: baseline and 6 months ]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
- Change in Quality of Life: MDADI [ Time Frame: baseline and 12 months ]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.
- Evaluation of Biomarkers [ Time Frame: throughout study completion, up to 2 years ]
- Objective Tumor Response [ Time Frame: 1 year ]Objective Tumor Response reported on participants at 1 year (complete, partial, progression, or stable response).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00573989
|United States, North Carolina|
|UNC Linberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|Wake Forest University Comprehensive Cancer Center|
|Winston-Salem, North Carolina, United States, 27157-1096|
|Principal Investigator:||Mercedes Porosnicu, MD||Wake Forest University Health Sciences|
|Principal Investigator:||Kathryn M. Greven, MD||Wake Forest University Health Sciences|