Comparison of Biomarker Modulation by Inhibition of EGFR and/or SRC Family
|Head and Neck Cancer Non Small Cell Lung Cancer||Drug: Erlotinib Drug: Dasatinib + Placebo Drug: Erlotinib plus Dasatinib Drug: Placebo||Phase 1|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
|Official Title:||Comparison of Biomarker Modulation by Inhibition of EGFR and/or Src Family Kinases Using Erlotinib and Dasatinib in Head and Neck Lung Cancers|
- The primary endpoints are comprised of a panel of tumor proteins to be obtained before after administration of the study drugs. [ Time Frame: 2-3 week preoperative period of drug administration ]
|Study Start Date:||January 2009|
|Study Completion Date:||February 2014|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm A
Erlotinib 150 mg
Erlotinib 150mg will be taken once a day for 14-21days.
Other Name: TarcevaDrug: Erlotinib
Erlotinib 150 mg for 14-21 days.
Other Name: Tarceva
Experimental: Arm B
Dasatinib + placebo
Drug: Dasatinib + Placebo
Dasatinib (100 mg) once a day for 14-21 days.
Other Name: Sprycel
Experimental: Arm C
Erlotinib (150 mg) plus Dasatinib (100 mg) for 14-21 days.
Drug: Erlotinib plus Dasatinib
Erlotinib (150 mg PO qD) plus Dasatinib (100 mg PO qD) 14-21 days
Other Name: Tarceva and Sprycel
Placebo Comparator: Arm D
Placebo for 14-21 days
Placebo for 14-21 days.
Background Head and neck squamous cell carcinoma (HNSCC) constitutes 3% of all malignancies and is the sixth most common malignancy worldwide. There will be an estimated 40,000 new cases and 11,000 deaths in the United States in 2007 and approximately 500,000 cases worldwide yearly . Squamous cell carcinoma accounts for at least 90% of all head and neck cancers. Surgical resection remains a standard treatment for patients with resectable HNSCC. For patients with high risk of local or distant relapse, radiation therapy (RT) alone, or in combination with chemotherapy, is given after surgery to improve loco-regional control and overall survival. Moreover, surgery often represents the only curative option in patients who relapse locoregionally. Non-small cell lung cancer (NSCLC) is the leading cause of death worldwide. NSCLC is infrequently diagnosed when the cancer can be eradicated with surgical extirpation.
- To determine the modulation of biomarkers by EGFR and/or Src targeting in head and neck and lung cancers.
- To determine if biomarker modulation is associated with reduction of tumor volume and/or evidence of histologic response in the tumor (e.g. decreased proliferation and/or decreased apoptosis) as well as safety and tolerability.
Subject population Patients will be accrued from head and neck and lung cancer patients who are surgical candidates. Surgery will be the primary curative treatment for patients enrolled in this study. Patients should not require any standard induction treatment prior to surgery. Surgery will have to be the best treatment option as determined by the treating physician. Therefore, we will not be delaying chemoradiotherapy or other curative treatment. We plan to include any stage of HNSCC or NSCLC that will be managed by primary surgery. If surgery is unexpectedly cancelled, the patient will be removed from the study unless there is an accessible lesion for biopsy. Ideally, the pre-treatment biopsy and the intraoperative sample will be obtained from the same site (when there are multiple lesions). Please see Section 3.0 for detailed eligibility criteria.
Treatment Plan The study drug or placebo will be taken for 14-21 days, and will be discontinued one day prior to planned surgical resection. If surgery is delayed, the study drug or placebo will be continued until one day prior to surgery, for up to a maximum of 28 days. Seven days is the minimum treatment for the patients to be evaluated. The interval between the last dose of experimental drug and surgery will be 12-36 hours. Please see Section 5.0 for treatment plan details. If the combination of erlotinib and dasatinib results in toxicity leading to a delay in surgery, the study will be terminated.
Statistical design and sample size This is a 4-arm randomized trial that is intended to estimate the effects of short-term preoperative therapy with EGFR and Src inhibitors upon a panel of biomarkers. The 4 treatment arms are erlotinib, dasatinib, their combination, and a placebo. We anticipate accruing 56 evaluable patients (14 patients per arm).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00779389
|United States, Pennsylvania|
|Hillman Cancer Center|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Jennifer R Grandis, MD||University of Pittsburgh|