Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Recurrence

Head and Neck Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Patients with Head and Neck or Non-Small Cell Lung Cancer who are Current or Former Smokers.

At Months 6, 12, 18, 24, 30, and 36, complete medical history will be recorded, and a physical exam will be performed by either a doctor or a nurse. At each of these visits, blood will be drawn for routine tests (about 3 teaspoons) and for research purposes (about 4 teaspoons). Also, a chest x-ray and a chest CT will be done at these visits.

Assessments

George Simon, MD

The goal of this research study is to look at how long individuals who have been treated for early stage NSCLC or HNSCC live without developing lung cancer. Another goal is to develop tools to help predict the likelihood of lung cancer occurrence in this population. This will be done by studying characteristics of tissue and bodily fluids (including blood).

Objectives:

* To assess the smoking-related disease-free survival in patients who are current or former smokers with a prior definitively-treated stage I/II lung or head and neck cancer.
* To develop a risk model to help predict the likelihood of lung cancer development both imaging and biomarker based in this high-risk population.

This study is known as the Vanguard Trial. When you enter this study, you will have a complete medical history (including smoking history) and physical exam, including measurement of height, weight, and vital signs (including blood pressure, heart rate, and temperature). You will have a performance status evaluation (a test looking at the ability to perform every day activities). You will have blood samples drawn for routine blood tests (about 3 teaspoons), to check your blood clotting function (about 1-2 teaspoons), and for research purposes (about 4 teaspoons). You will have a chest x-ray and a CT scan of your chest. Women who are able to have children must have a negative blood or urine pregnancy test. If you are currently a smoker, you will be given information on programs to help you quit smoking. Although you will be encouraged to quit smoking, you do not have to quit smoking or participate in these programs to be a part of this study.

You will also have a bronchoscopy (tissue sample from the lung) at the beginning of this study for lab analysis. For this procedure, you will be given drugs to relax. Then, a local anesthetic will be sprayed in your nose and throat to numb those areas. A slim, flexible tube with a light will be placed through your nose or mouth and into your lungs. Tweezers will be fed through the tube to collect lung tissue (biopsy) samples from 6 different places in your lungs. During the bronchoscopy procedure, a complete inspection of the airways will be performed. Any suspicious areas that are seen under the white-light and autofluorescence bronchoscopy will be identified and more biopsies and brushings will be performed to evaluate whether any pre-cancerous tissue is present. You will also have a bronchial brushing next to each biopsy site. In a bronchial brushing, a small brush is fed through the tube into your lungs and a sample of lung tissue is gently scraped off. When the biopsies and brushings are done, you will have a bronchial lavage (bronchial washing). In the bronchial lavage, a small amount of water (about 4 tablespoons) is sprayed into your lungs and then suctioned out through the tube. This fluid is used to collect additional tissue and mucous samples. In addition, a sputum (saliva) sample will be taken and the inside of your cheek will be scraped (buccal sample).

If you have had HNSCC, you will also have a laryngoscopy. In a laryngoscopy, a lighted tube is placed down your throat and the larynx is checked. The back of your throat will be sprayed with an anesthetic before this procedure to make the procedure more comfortable.

While on study, you will return to the clinic for at least 3 years and for up to a total of 6 years. At Months 6, 12, 18, 24, 30, and 36, your complete medical history will be recorded, and you will have a physical exam by either a doctor or a nurse. At each of these visits, you will also have blood drawn for routine tests (about 3 teaspoons) and for research purposes (about 4 teaspoons). You will also have a chest x-ray and a chest CT at these visits. At Months 12, 24 and 36, you will have blood drawn (about 1-2 teaspoons) to check your blood-clotting function. If you think you may be pregnant, you will also have a urine or blood pregnancy test. In addition, you will have a bronchoscopy and provide sputum and buccal smear samples at your 12 month visit. If you have been treated for HNSCC you will have a laryngoscopy at 12 months.

You have the right to leave the study at any time. If you choose to stop participating in this study, you will be asked to return to the clinic for a final clinic visit. At this visit, your complete medical history will be recorded, and you will have a physical exam and blood drawn for routine tests (about 3 teaspoons) and for research purposes (about 4 teaspoons). Your study doctor will also ask you about your current smoking use, any medications you are taking, and how you are feeling (symptoms).

This research study includes two bronchoscopies done one year apart. These bronchoscopies are being done primarily for research purposes and are unlikely to provide information useful in your individual treatment. These bronchoscopies do have risks associated with them. These risks are described in section 4 of this informed consent document.

Recent research on early stage NSCLC indicates that adjuvant chemotherapy after surgery increases the length of time a person may survive and the length of time before cancer recurs. However, this adjuvant chemotherapy also has side effects that can be severe and in rare cases fatal. If you have had surgery for NSCLC and wish to receive adjuvant chemotherapy, you may only enroll in the Vanguard study after you have completed the adjuvant chemotherapy.

As part of this study you will provide samples of your lung tissue, saliva, blood, and scrapings from the inside of your cheek. Fluid and mucous collected during the bronchoscopies will also collected. These samples will be studied by scientists to learn about genes and proteins in people who have been treated for early NSCLC or HNSCC. The samples will also be used to grow cells and cultures that will be used to test chemotherapy drugs. These cells and cultures will also be used to learn about genes and proteins.

All M. D. Anderson researchers are trained in the importance of maintaining patient privacy. Your privacy will be protected by assigning you a number that will be used in place of your name on documents that are part of this study. A list that links your name with your study number will be stored in a restricted file that may be accessed only with a password. Only a few essential research personnel have access to this password.

At the end of the study you will not be automatically notified of the research findings. If you wish to learn about the results, however, you may request them from the principal investigator:

Principal Investigator: Waun Ki Hong, MD 1515 Holcombe Blvd., Unit 432 MD Anderson Cancer Center Houston, TX 77030

This is an investigational study. A total of about 50 individuals will take part in this study. Participants will be enrolled at M. D. Anderson and several other sites around the country.

Samples of lung tissue, saliva, blood, and scrapings from inside of cheek. Fluid and mucous collected during bronchoscopies.

Vanguard Study for Head and Neck Cancer or Non-Small Cell Lung Cancer (NSCLC) Patients

Vanguard Study Characterizing Occurrence of Recurrent or Second Primary Tumors in Patients With Prior History of Definitively Treated Stage I/II Head and Neck or Non-Small Cell Lung Cancer Who Are Current or Former Smokers

Smoking-related disease-free survival (S-DFS) defined as time from registration to the development of recurrence, smoking related SPT, or disease-specific death, whichever occurs first.

United States Department of Defense

M.D. Anderson Cancer Center

Musculoskeletal Diseases

Nervous System Diseases

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Carcinoma, Squamous Cell

Papilloma

Muscle Rigidity

Oropharyngeal Neoplasms

Hypopharyngeal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Hypopharyngeal Cancer

Central Nervous System Depressants

All Drugs and Chemicals

Anesthetics

Tetracaine

Laryngoscopy is performed under general anesthesia with a rigid laryngoscope. Mucosal surfaces of the oropharynx, hypopharynx, and glottis (base of tongue, vallecula, epiglottis, aryepiglottic folds, arytenoids, piriform sinuses, true and false vocal cords, and esophageal inlet) are systematically visualized. Areas of irregularity are biopsied with 2mm and/or 4mm cupped forceps. Esophagoscopy and bronchoscopy will be performed per the standard of care.

Direct Rigid Endoscopy

Transnasal flexible endoscopy with and without narrowband imaging- additional diagnostic test. This examination is performed after topical intranasal anesthesia with 2% Pontocaine spray. A fiberoptic laryngoscope is passed into the nasal cavity to the pharynx where mucosal surfaces of the UADT can be visualized. The optics of a standard fiberoptic scope are generally considered to be inferior to direct visualization. The addition of narrowband imaging does not change the procedure, but enhances visualization of the mucosal vasculature. Biopsies are performed through a second channel in the endoscope with 1.8mm cupped forceps and will require an additional dose of topical anesthesia.

Transnasal Flexible Endoscopy with Narrowband Imaging

Mark S. Courey, MD

This study will compare TNFE-NBI and biopsy, with DRE and biopsy for the diagnostic evaluation and staging of patients with suspicious UADT lesions. All patients enrolled in the study will undergo TNFE-NBI with biopsy of suspicious lesions prior to planned regular clinical care (DRE). Biopsies will be evaluated by standard clinical methods for patient diagnoses and care. As the current standard of care, if all biopsies for a given patient are non-malignant, a 3 month office visit will be arranged to evaluate and determine the need for further intervention. At the end of study enrollment both sets of biopsies will be re-evaluated in a blinded fashion by the surgical pathologist. Study assessment of malignant vs. non-malignant (benign) pathology will be used to see whether both tests tended to agree on diagnoses.

This is a single arm prospective study to evaluate the concordance between a standard-of-care diagnostic procedure and TNFE-NBI for diagnosing malignancy. The primary aim of this investigation is to determine whether the TNFE NBI procedure can detect and stage cancer in the head and neck as well as the standard DRE which requires general anesthesia.

Patients who are pending direct laryngoscopy after presenting to the Department of Otolaryngology-Head and Neck Surgery at UCSF with UADT lesions will be asked to participate in the study provided all eligibility criteria are met. Under current standard-of-care for diagnostic evaluation and staging of UADT lesions, patients will undergo imaging studies including CT and/or MRI of the neck with contrast prior to direct laryngoscopy. Study participants will undergo both the TNFE NBI and DRE procedures.

The study procedure TNFE NBI will be performed, followed 1-6 weeks later by DRE, the standard approach for diagnosis, without the surgeon having knowledge of the details of the first procedure. The sequence of examinations in this investigation is dictated by the need to minimize mucosal trauma during the first examination and allow for mucosal healing prior to the second examination, and thus cannot be randomized. TNFE-NBI produces much less mucosal trauma by avoiding direct blunt manipulation and through the smaller, 1.8mm, cupped biopsy forceps.

Because it is possible that the TNFE NBI procedure might detect smaller tumors or lesions in different locations, the biopsy locations from the TNFE NBI procedure will be made known at the end of the DRE surgery to ensure that all needed areas are biopsied. Therefore, a secondary aim of this study will be to explore whether the TNFE NBI procedure may improve the detection of malignancy when added to the DRE surgery.

Patients enrolling in the study will undergo TNFE-NBI with biopsy of suspicious lesions. The TNFE-NBI examinations will be digitally recorded. The examiner will describe, using standard language and diagrams, anatomic location of suspicious areas revealed during the procedure. Biopsy tissue will be labeled as to the area of origin.

In the event that a participant does not tolerate TNFE-NBI, the study procedure will be aborted.

At least one week and no more than 6 weeks after TNFE-NBI, patients will undergo standard of care direct rigid endoscopy. The intervening time to DRE is to allow for recovery of mucosal surfaces.

Participants who did not tolerate TNFE-NBI will undergo DRE as standard of care.

The DRE examiner will be blinded as to which areas were biopsied during the TNFE-NBI procedure until completion of the standard of care DRE examination and tissue biopsy selection. In the investigator's experience, areas of prior biopsy will not be apparent to the DRE examiner as mucosal recovery will occur during 1-6 weeks elapsing between TNFE-NBI and DRE. Upon completion of the standard of care DRE examination and tissue biopsy selection, the DRE examiner will open the TNFE-NBI examiner's note describing the areas deemed suspicious during TNFE-NBI. Additional areas may then be examined and biopsied with DRE based on the TNFE-NBI note. Records will be kept as to which anatomic areas were:

1. identified by both procedures,
2. identified by DRE only after prompting by the TNFE-NBI note
3. identified by DRE only (not previously identified by TNFE-NBI).

A diagnosis of carcinoma in situ or invasive squamous cell carcinoma will be considered positive for malignancy. If a diagnosis of malignancy is made after the initial endoscopy, regardless of which test was positive, the patient will be contacted immediately so that appropriate treatment can be pursued. For diagnoses of dysplasia and other non-malignant conditions such as polyp, lymphoid tissue, papilloma, etc., the patient will be scheduled for follow-up.

Routine follow-up of benign lesions includes a routine head and neck examination, including indirect laryngoscopy with a fiberoptic endoscope 2-3 months after biopsy. New or enlarging lesions will be assessed in the operating room with DRE per standard of care. Lesions initially diagnosed as non-malignant that are stable or not visualized at follow-up will not need re-biopsy per standard of care.

At the conclusion of study enrollment, all biopsy specimens will be de-identified, batched, and evaluated by a pathologist blinded to the type of endoscopy. A diagnosis of carcinoma in situ or invasive squamous cell carcinoma will be considered positive for malignancy.

If patients with non-malignant diagnoses of study pathology (both TNFE-NBI and DRE) have been diagnosed with malignancy at or before routine follow-up, the study evaluation will be considered a false negative. If no malignancy developed within three months of the biopsy procedures, the study evaluation will be considered a true negative. (This design represents a compromise in evaluating patients with a negative endoscopy. By necessity a negative diagnosis is one of exclusion, given that complete pathologic evaluation of every patients' upper aerodigestive tract is neither ethical, practical, nor feasible in clinical practice. Precedent for this design can be found in Smith-Bindman, Chu et al. 2005)

Concordance of Two Endoscopic Procedures for Diagnosis of Carcinoma of the Upper Aerodigestive Tract

Accuracy of Endoscopic Diagnosis of Carcinoma of the UpperAerodigestive Tract: A Tandem Trial of Direct Rigid Endoscopy and Transnasal Flexible Endoscopy With Narrowband Imaging

At the conclusion of study enrollment, all biopsy specimens will be coded, de-identified, and re-evaluated by the study pathologist in a blinded fashion. The code will be broken for the purposes of study analyses.

If all biopsies taken by both procedures on each patient are diagnosed as non-malignant upon blinded evaluation by the study pathologist or if both procedures have at least one biopsy diagnosed as malignant, this will be considered concordance.

Describe differences, if any, in characterization of AJCC cTNM stage and tumor location as determined by TNFE-NBI as compared to standard-of-care DRE

describe differences, if any, in biopsy location during TNFE-NBI as compared to standard-of-care DRE

To describe the frequency of detecting malignancy at a 3-month follow-up for patients initially diagnosed as negative for malignancy by both TNFE NBI and DRE evaluations

The frequency by grade for all adverse events will be tabulated by type and procedure as well as timing (during or immediately following study procedure vs. follow-up).

Patients who have fulfilled the inclusion criteria and are unable to tolerate the unsedated examination will be classified as having non-concordance between TNFE-NBI and DRE (because a diagnosis could not be made based upon pathology) and the reason for intolerance to the procedure recorded.

University of California, San Francisco

Patients undergo flexible scope intubation up to 2 attempts following induction of general anesthesia and adequate manual ventilation. In case of failed 2 attempts, patients undergo a third attempt utilizing another technique or device.

Patients undergo flexible scope intubation and video laryngoscopy up to 2 attempts following induction of general anesthesia and adequate manual ventilation. In case of failed 2 attempts, patients undergo a third attempt utilizing another technique or device.

Laryngoscopy

Tracheal Intubation

Carin Hagberg

Carin A. Hagberg

This trial studies how well flexible intubation scope with or without video laryngoscope works in supporting endotracheal tube placement in patients with head and neck cancer before surgery. Flexible intubation scope and video laryngoscope are devices that have a small camera to help the doctor see the patient's airway on a screen. Both devices may help the doctor who gives anesthesia prevent complications from placing the breathing tube (such as pain or mouth injury).

PRIMARY OBJECTIVES:

I. To compare the rates of difficult endotracheal tube (ETT) placement using a flexible intubation scope (FIS) versus a combination of flexible intubation and video laryngoscopy in difficult airway management.

SECONDARY OBJECTIVES:

I. To compare the ease of using a flexible intubation scope (FIS) with and without the use of the video laryngoscope (VL).

II. Total time for securing the airway.

III. Number of attempts required for intubation.

IV. Rate of failure at intubation.

V. Incidence of desaturation.

VI. Assessment for hoarseness, sore mouth, neck, or jaw, dysphonia, dysphagia, lip injury, tongue injury, or tooth damage.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo flexible scope intubation up to 2 attempts following induction of general anesthesia and adequate manual ventilation. In case of failed 2 attempts, patients undergo a third attempt utilizing another technique or device.

ARM B: Patients undergo flexible scope intubation and video laryngoscopy up to 2 attempts following induction of general anesthesia and adequate manual ventilation. In case of failed 2 attempts, patients undergo a third attempt utilizing another technique or device.

Flexible Intubation Scope With or Without Video Laryngoscope in Supporting Endotracheal Tube Placement in Patients With Head and Neck Cancer Before Surgery

Flexible Scope Intubation vs.Flexible Scope Intubation and Video Laryngoscopy Combination: A Prospective Randomized Clinical Trial

Estimated rates of difficult ETT will be provided using exact 95% confidence interval (CI) using the method of Clopper-Pearson.

For complications, researchers will assign a '0' for no complication arising and a '1' for any complications arising. The total score will range from 0 to 3 and will be summarized using frequencies and percentages related to each level of the total score and using the mean score and standard deviation, whichever is more appropriate.

National Cancer Institute (NCI)

Laryngeal Diseases

Laryngeal Neoplasms

Laryngeal Cancer

Antineoplastic Agents

Docetaxel

Fluorouracil

Cisplatin

Tubulin Modulators

Antimitotic Agents

Decision between surgery and Chemo-rt according to response to initial induction chemotherapy

Treatment of advanced larynx cancer with induction TPF, in order to decide between chemoradiation and laryngeal preservation surgery

laryngoscopy

Taxotere 75 mg/m2 D1, Cisplatin 75 mg/m2 D1, 5FU 750 mg/m2 D1-4

Taxotere (Docetaxel), Cisplatin, 5FU

Aron Popovtzer, md

Raphael Feinmesser, md

Aron Popovtzer, MD

Salomon Stemmer, MD

Treatment of patients with one cycle of induction chemotherapy to select for organ preservation of the larynx has been proven as a standard approach. When compared to historical controls. The investigators propose to study patients with a similar treatment strategy (i.e. one cycle of induction chemotherapy followed by two more chemotherapy cycles, in advanced nodal disease, followed by chemoradiation for those responding to the initial chemotherapy. Those who fail to respond or fail in radiation will directly undergo surgery. The novelty of the proposed study is that non responders and failures will be given the opportunity of larynx preserving supracricoid laryngectomy. The investigators will attempt to reduce toxicity from induction chemotherapy and improve potency with the use of docetaxel/cisplatin/5-fluorouracil (TPF) in place of the standard regimen of cisplatin and 5-fluorouracil (PF). Emerging data demonstrates that induction regimens containing triplets with platinum, 5-fluorouracil, and taxanes produce higher response rates and less overall toxicity when compared to induction strategies utilizing PF

The optimal treatment of patients with laryngeal cancer remains controversial. Standard treatment options have included laryngectomy with or without radiation (RT) and radiation alone with surgical salvage (RTSS).

Because of the significant functional morbidity associated with laryngectomy, the Department of Veterans Affair Cooperative Studies Program completed a randomized, prospective study of 332 patients that compared a new organ preservation treatment strategy to conventional laryngectomy and radiation. The experimental treatment arm involved three cycles of neoadjuvant chemotherapy followed by definitive radiation among patients who had a partial (\>50%) clinical tumor response. Final results of this study demonstrated comparable 2, 3, 4, and 10 year survival rates between treatment groups, with successful laryngeal preservation in 66% of the surviving patients randomized to receive neoadjuvant chemotherapy.

This study led to a dramatic re-assessment of the treatment approach for advanced laryngeal and hypopharyngeal cancer patients, who face total laryngectomy. Based on these results, Second approach was designed and tested in a Phase II study at the University of Michigan .In this study, 97 patients were treated with one cycle of induction chemotherapy. Seventy-five percent had a \>50% reduction of tumor and were treated with chemo-RT (cisplatin 100 mg/m2 x 3 cycles), and 25% were non-responders who underwent total laryngectomy followed by RT. The overall 3-year survival rate was 85%,and the larynx preservation rate was 70%. This study included over 30 percentage of patients with advanced stage 4 disease, however did not specifically evaluate there outcome and therefore did not directly address the role of organ preservation in advanced disease which is considered a controversial issue in head and neck literature.

In this study all patients (25 %) who did not respond to the initial chemotherapy were referred to total laryngectomy and therefore there were 30 %of patients who eventually underwent total laryngectomy.Lately several series suggest the option of partial laryngectomy as an alternative to total laryngectomy as initial treatment for advanced larynx cancer ,in cases in which the cricoids cartilage and arytenoids are not involved.Supracricoid subtotal laryngectomy spares at least one arytenoid and offers organ preservation and can also be performed according to many articles as salvage surgery in cases of radiation failure,and therefore if performed in the right indications can improve the percentage of total laryngectomy free patients without compromising survival. This will reflect of course on quality of life It has been suggested lately that the use of aggressive induction chemotherapy may improve outcome. The combination of Taxotere with Cisplatin and 5-fluorouracil has been shown to be more effective than the standard cisplatin and 5-fluorouracil without an elevation in side effects .It has been suggested that the three cycles of induction chemotherapy may lower the rate of distant metastases which is high in advanced disease

Objectives

Primary

To determine the laryngeal preservation rate in a treatment paradigm that uses clinical response to a single cycle of induction chemotherapy to select patients for either concurrent cisplatin-radiation or surgery(if possible organ preserving partial laryngectomy) as compared to historical controls To determine the survival rate among T4 laryngeal patients in a treatment paradigm that uses clinical response to a single cycle of induction chemotherapy to select patients to either ,two more cycles of induction followed by concurrent cisplatin-radiation or surgery .

Secondary To determine the survival rate in a treatment paradigm that uses clinical response to a single cycle of induction chemotherapy to select patients for either concurrent cisplatin-radiation or surgery including organ preserving partial laryngectomy (if possible) as compared to historical controls.

To determine if the use of three cycles of induction chemotherapy lowers the rate of distant metastases in advanced cases; namely: positive nodal disease and T4.

To evaluate the quality of life (QOL) of this treatment paradigm.

To evaluate partial supracricoid laryngectomy as salvage to chemoradiation failure.

compare PET scan results with the pathological specimen of the larynx.

To determine correlation between changes in biological markers such as EGFR degradation EGFR mutation, p53 overexpression, Bcl-XL, Bcl-2 expression, and HPV observed in tumor biopsies taken shortly after the administration of TPF, compared with pre-treatment biopsies. And compared to those found in the completion of treatment in cases of failures.

Study Design

Chemotherapy/Radiation/Surgery schedule Days #1-4: Patients will undergo induction chemotherapy with (TPF) docetaxel (Taxotere) 75 mg/m2 and cisplatin 100 mg/m2 on day 1, and 5-FU CI 750mg /m2 /24 hours days 1-4. See section 7.2.

Day #22: Patients will undergo a direct laryngoscopy with biopsy the biopsy will be done with in 3 days. Patients will also undergo a repeat CT scan of the neck within a week (+/-) of their perspective biopsies.

Patient with a \< 50% response (NR) to induction chemotherapy will undergo salvage supracricoid partial laryngectomy if possible or laryngectomy followed by RT. Cisplatin will be added to radiation for patients whose surgical pathology reveals high-risk features (i.e. extracapsular spread, \> 2 positive lymph nodes, perineural invasion, or positive margins). Cisplatin will be dosed 35 mg/m2 weekly at the discretion of the prescribing physician. See section 7.2 for prescribing details for cisplatin.

Responding patients with \> 50% response will be divided to two groups those with N2 disease or stage T4 will undergo two more cycles with induction TPF others will directly undergo treatment with RT (Total dose 70 Gy) in combination with cisplatin weekly (35mg/m2 ).Those who receive two more chemotherapy courses will be assessed clinically and by CT scan if no PD will continue to chemo and RT ,those with PD will undergo surgery Eight weeks following the completion of RT, patients will undergo a repeat direct laryngoscopy and a PET scan. The primary tumor site will be biopsied. Neck nodes that are persistent, clinically suspicious nodes, including PET positive nodes, will be biopsied. Patients with positive laryngeal biopsies following chemoradiation will undergo salvage surgery if possible supracricoid partial laryngectomy, otherwise laryngectomy. If the laryngeal biopsy is negative but clinically positive neck lymph nodes remain, patients will undergo neck nodal dissection.

Once patients are disease-free following chemoradiation and nodal neck dissections (if needed), patients will be followed every 6 weeks in the first year, followed by every 3 months in the second, every 6 month between 2 and 5 years. Patients whose physical examination or whose imaging studies are concerning for recurrent disease will undergo biopsy. If positive, they will undergo salvage laryngectomy.

Chemotherapy with Cisplatin, Docetaxel, and 5-Fluorouracil (TPF)

Docetaxel (Taxotere): Docetaxel 75 mg/m2 administered as an i.v. infusion over one hour on day #1.

With Docetaxel administration, all patients will receive dexamethasone 8 mg PO BID for 3 consecutive days, starting 1 day before docetaxel administration, or 10-20 mg IV on Day 1 prior to treatment with Docetaxel.

Cisplatin: Cisplatin 100 mg/m2, administered as an i.v. infusion will run over one hour on day #1 following docetaxel.

An aggressive antiemetic regimen is required before the administration of cisplatin, consisting of a serotonin antagonist, APREPITANT and a steroid.

5-Fluorouracil: 5-Fluorouracil 750 mg/m2 in 0.9% normal saline as a 24-hour continuous infusion, day's #1-4. The infusion will start after cisplatin administration.

Evaluation of Response to Treatment

Careful evaluation of tumor extent will be separately recorded for the primary tumor and regional nodes at specified intervals. These will be based on laryngoscopies performed pre-treatment, day 21 after start of induction chemotherapy, and 8 weeks after completion of chemoradiation. Standardized response criteria will be used. CT scans will be used at the discretion of the clinician to supplement clinical exams.

7.4.2 Biopsy of any persistent neck nodes is required if at the 8 week post -radiation evaluation is either clinical or radiologically positive. . Patients whose PET shows a CR at 8 weeks post will undergo clinical observation.

Diagnostic CT scans and/or PET scans will be obtained prior to scheduled endoscopies for tumor assessment. Post treatment a ct will be performed.

Outpatient clinical examinations will be performed at the completion of radiation therapy, at 6 week intervals during year 1 of follow-up,every 3 months during year 2 of follow-up, and 6-monthly during year 3 of follow-up. 8 Translational Studies

Tissue samples obtained at the time of laryngeal biopsies will be sent to laboratories for analysis of histologic growth pattern, p53 overexpression, Bcl-XL, Bcl-2 expression, HPV , EGFR expression, phosphorylated EGFR and stem cells levels . The tissue will be obtained during routine biopsies prior to the beginning of treatment, after completion of induction chemotherapy and after Radiation .the following techniques will be used: Immunohistochemistry, PCR and Western blot.

10 Response Assessment Criteria:

The patient's tumor will be tattooed by the surgeon,who will then measure the product of the longest primary tumor dimension and its perpendicular; following chemotherapy, the extent of the tumor will be measured for response. Treatment decisions (i.e. surgery vs Chemo+RT) are based on response of the tumor at the primary site.

Tumor responses to chemotherapy or chemoradiation will be determined clinically by the surgeon performing the DL.

Radiologic imaging studies will be used in conjunction with the physical examination in determining tumor response to chemotherapy or chemoradiation.

Clinical PR: Significant (\>50%) reduction in the product of the longest primary tumor dimension and its perpendicular compared to pre-treatment clinical (endoscopic) measurements or imaging study as necessary.

Non-Responders (\< PR): A 50% or less reduction in the product of the longest primary tumor dimension and its perpendicular compared to pre-treatment clinical (endoscopic) measurement or imaging study as necessary.

Criteria for Discontinuation of Treatment

1. Unacceptable adverse event(s).
2. Intercurrent illness, which prevents further administration of treatment.
3. Patient preference.
4. Progressive disease.
5. Life threatening or other unacceptable drug-related toxicity.
6. General or specific changes in the patient's condition that render the patient unacceptable for further treatment in the judgment of the investigators.

Radiation Therapy

13.1. General Considerations: All the patients in this study will receive either definitive radiotherapy or post operative irradiation. For those patients found to have a PR to induction therapy on repeat DL, definitive radiotherapy with Cisplatin will begin. Post operative radiation should begin as soon as adequate healing has been established. Usually, this will be within three to four weeks of the surgical procedure but must begin by six weeks.

13.2 Radiation Fields: The treatment volumes will be individual as for each patient depending upon the extent of disease. Tumor volumes will be outlined on the planning CT scans with the aid of pre-chemotherapy CT and, if available, PET scans, to ensure adequate irradiation of the pre-chemotherapy tumor volume. Treatment techniques will aim at adequate irradiation of the clinical and the sub-clinical disease. The therapy goals, specifying the intended doses to the primary tumor and lymph node metastases, and the intended doses to each lymph node level treated adjuvantly, will be detailed in the therapy chart. A CT-based display of the isodoses will be recorded, such that it will be feasible to assess whether the intended (prescribed) isodoses cover the targets adequately.

Doses:

Radiation with chemotherapy: Tumor doses will be expressed in Gy. The prescribed doses should encompass the targets. Treatment plans will be generated demonstrating adequate coverage of the target volume. The dose across the target volume should not vary by more than +/- 10% of the prescribed dose.The treatment will be given either using IMRT planning or 3D. Treatment will be given once daily, five days per week, two Gy per fraction to gross disease, and 1.6-2.0 Gy per fraction to subclinical disease. Total gross dose will be 70 Gy and subclinical disease dose will be 50-60 Gy.

Post Operative Radiation Therapy: The patient will be treated with conventional fractionation, 1.8-2.0 Gy per fraction, and five fractions per week in a continuous course. The dose to the tumor bed and lymph nodes will be 56-64 Gy, depending of the existence of extranodal extension or the existence of close surgical margins. Patients with gross residual disease or positive resection margins will receive total 66-70 Gy to the sites of residual disease.

Salvage Surgery

The extent of salvage surgery for either the primary tumor or regional nodes is dictated by the extent of the disease .

Salvage surgery may be required at the times of scheduled tumor assessments or any time tumor progression or recurrence is demonstrated by adequate biopsies of areas clinically suspicious for tumor involvement.

Primary site: Extent of surgery will vary between total laryngectomy and supracricoid subtotal laryngectomy in accordance with the inclusion and exclusion criteria specified).

Neck: Bilateral selective neck dissections will be performed in conjunction with salvage total laryngectomy for any patient initially staged N0 in the neck. Ipsilateral modified radical or radical neck dissection is required for any patient initially staged N+ who recurs or persists with cancer in that neck. At 8 weeks post radiation, neck dissection alone without laryngectomy is required for any patient with initial staging neck node \> 3 cm in size who is PET positive or with biopsy proven palpable neck disease. 14.5

Informed Consent

All patients with stage III and IV squamous cell carcinoma of the larynx who are candidates for surgical resection will be screened for participation in this study.

.

Reporting Potentially Serious Adverse Events

Definitions

An adverse event is any new, undesirable medical experience or Change of an existing condition which occurs during or after treatment, whether or not considered product-related.

A serious adverse event is any untoward medical occurrence that

Suggests significant hazard or side effect that:

1. Results in death.
2. Is life-threatening (places the patient at immediate risk of death).
3. requires or prolongs inpatient hospitalization Is disabling or incapacitating.

Induction Docetaxel/Cisplatin/5-fluorouracil (TPF) as Selector for Chemo Radiation Therapy (RT) Versus Partial Laryngectomy in Advanced Laryngeal Cancer

Phase II Organ Preservation Trial Using Cisplatin Concomitant With Radiation Therapy in Advanced Laryngeal Cancer Patients Who Have Responded to Induction Chemotherapy With Taxotere, Cisplatin, and 5-Fluorouracil (TPF)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Vanguard Study for Head and Neck Cancer or Non-Small Cell Lung Cancer (NSCLC) Patients	NCT00352391	Head and Neck C... Lung Cancer	Assessments	18 Years -	M.D. Anderson Cancer Center
Concordance of Two Endoscopic Procedures for Diagnosis of Carcinoma of the Upper Aerodigestive Tract	NCT01175499	Upper Aerodiges... Neoplasms, Orop... Oropharyngeal C... Neoplasms, Hypo... Hypopharyngeal ... Head and Neck N... UADT Neoplasms Carcinoma, Squa... Papilloma	Direct Rigid En... Transnasal Flex...	18 Years -	University of California, San Francisco
Flexible Intubation Scope With or Without Video Laryngoscope in Supporting Endotracheal Tube Placement in Patients With Head and Neck Cancer Before Surgery	NCT03757091	Head and Neck N...	Laryngoscopy Tracheal Intuba...	18 Years -	M.D. Anderson Cancer Center
Induction Docetaxel/Cisplatin/5-fluorouracil (TPF) as Selector for Chemo Radiation Therapy (RT) Versus Partial Laryngectomy in Advanced Laryngeal Cancer	NCT01073683	Larynx Cancer	laryngoscopy Taxotere (Docet...	18 Years -	Rabin Medical Center

Spots Global Cancer Trial Database for laryngoscopy

Every month we try and update this database with for laryngoscopy cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.