Neoplasms

All Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Carcinoma

Carcinoma, Squamous Cell

Oropharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Etoposide

Carboplatin

Cisplatin

Etoposide phosphate

Enzyme Inhibitors

Patients treated with three cycles neoadjuvant chemotherapy who do not exhibit response to chemotherapy are then allocated to recieve standard dose and schedule radiotherapy.

Patients who respond to chemotherapy are treated with reduced dose radiotherapy.

Chemotherapy for three cycles prior to radiotherapy

chemotherapy

Standard radiotherapy for non-responders vs reduced dose radiotherapy for responders.

radiotherapy

Patients who achieve a response to chemotherapy then go on to receive reduced dose radiotherapy.

Reduced dose radiotherapy

Bhoomi Mehrotra, MD

This study looks at the use of three cycles of chemotherapy given prior to radiation therapy in patients with cancer of the oral cavity and evidence of prior exposure to Human Papilloma Virus (HPV). Patients with cancer of the oral cavity who have evidence of exposure to HPV have a better prognosis than those who do not have such evidence of exposure to HPV. The main hypothesis of this study is that using three cycles of chemotherapy prior to embarking on radiation therapy will allow the use of reduced doses of radiation therapy and, therefore, less radiation induced side-effects. The primary objective is to determine the activity of this pre-radiation chemotherapy strategy along with reduced dose levels of radiation with or without chemotherapy during the radiation phase. The effectiveness of the strategy will be assessed at three months following the completion of the radiation therapy phase and also at two years following completion of the radiation therapy.

Induction Chemotherapy TPF induction chemotherapy will be administered as published from the TAX 323 phase III trial. Specifically, each cycle will consist of docetaxel at a dose of 75 mg per square meter, administered as a 1-hour infusion on day 1, followed by cisplatin at a dose of 75 mg per square meter, administered as a 1-hour infusion on day 1, and fluorouracil at a dose of 750 mg per square meter per day, administered by continuous infusion on days 1 to 5. Induction chemotherapy will be given every 3 weeks for three cycles, unless there is distant disease progression, unacceptable toxic effects, or withdrawal of consent by the patient. All patients will be required to have a continuous venous access device such as a PICC line or Infusaport type device. This is standard of care for continuous infusion fluorouracil. Response assessment by examination, contrast-enhanced CT imaging and whole body PET-CT will be performed after the third treatment cycle. Radiotherapy or chemoradiotherapy will commence within 3-4 weeks from the conclusion of the induction program.

Selection for Radiation Alone vs. Chemoradiotherapy For CR/PR patients with CR at primary site following induction chemotherapy, locoregional therapy will be risk-adjusted according to baseline tumor stage/characteristics. Local therapy will be 1) radiotherapy as a single modality for Tx (T1-2), T0-1 or exophytic T2, N0-2a disease, or will be 2) concomitant chemoradiotherapy for Tx (T3), endophytic T2, T3, N2b-c disease. Patients with PR at primary site will receive concurrent chemotherapy and reduced dose radiation.

All SD/PD patients will receive concurrent chemotherapy and full dose radiation. Patients catalogued with disease progression on the basis of new distant metastatic disease spread (DM) during induction chemotherapy will be taken off protocol for consideration of palliative therapy.

Concurrent Chemotherapy Concurrent chemotherapy will consist of cisplatin given at 35 mg/m2 weekly for six cycles OR carboplatin given at AUC 1.5 weekly for six cycles. Concurrent chemotherapy will start during the first week of radiation treatment. Selection of either schedule will be left to the discretion of the attending medical oncologist. Concurrent chemotherapy will be held for a platelet count of \<100,000 or an absolute neutrophil count of \< 1000 per cubic mm.

IMRT doses Primary Target (residual gross disease): 66 Gy called CTV1 (2.2 Gy/fraction in 30 fractions).

Intermediate-Risk Target: 57 Gy called CTV2 (1.9 Gy/fraction in 30 fractions). Prophylactic Target Coverage: 54 Gy called CTV3 (1.8 Gy/fraction in 30 fractions).

IMRT planning Treatment planning CT scans will be required to define target volumes. The treatment planning CT scan should be acquired with the patient in the same position and immobilization device as for treatment. All tissues to be irradiated must be included in the CT scan. MRI or whole body PET/CT scans may be included to assist in definition of target volumes, especially when primary or retropharyngeal nodal disease extends near the base of skull. The immobilization device should include neck and shoulder immobilization. GTV, CTVs, PTVs, and normal tissues must be outlined on all CT slices in which these structures exist.

Primary Target CTV1: All regions of GTV-R in PR patients will receive 66 Gy in 30 fractions, with no attempt to cover remainder of initial GTV. There will be no CTV1 in CR patients.

Intermediate-Risk Target CTV2: This volume encompasses all initial primary and nodal GTV volumes, regions adjacent to GTV (e.g. contralateral base of tongue), as well as complete anatomic coverage of involved cervical neck levels. This will receive 57 Gy in 30 fractions.

Prophylactic Target Coverage CTV3: This volume covers all uninvolved at-risk nodal basins. This will receive 54 Gy in 30 fractions.

Low Neck Conventional Field Treatment: Bilateral low neck/supraclavicular fossae will initially be treated with a beam-split AP field to 40 Gy in 20 fractions with a 3x3 cm larynx block matched at central axis with the inferior edge of IMRT treatment fields. Treatment will then continue to 50 Gy with a midline cord block over 5 daily fractions. Cone-down AP mid neck boosting to 56 Gy will be administered to low neck CTV2, down to the superior edge of the clavicle. Treatment will continue to 64 Gy for low neck CTV1 volumes, respecting brachial plexus dose limitations.

Dose specification The prescription dose is the isodose which encompasses at least 95% of the PTV. No more than 20% of any PTV will receive \>110% of its prescribed dose. No more than 1% of any PTV will receive \<93% of its prescribed dose. No more than 1% or 1 cc of the tissue outside the PTVs will receive \>110% of the dose prescribed to the primary PTV.

Fractionation and treatment duration Treatment will be delivered once daily, 5 fractions per week, over 6 weeks. All targets will be treated simultaneously. Breaks in treatment should be minimized. Break in treatment time of more than 5 days will be considered a major variation and requires documentation underlying the specific reasons for the treatment break (ex. related to study drug and/or chemotherapy and/or RT).

Functional Quality-of-Life Assessments Clinical Assessment of Treatment-Related Symptoms, and Dietary Status: MDASI-HN and MDADI instruments will be self-administered by all study subjects at baseline, treatment completion, and at routine post-radiation surveillance appointments over the subsequent 24 months. At these time points, nutritional status will also be assessed by weight, normalcy of diet score based on the results of the PSS-HN, and feeding tube dependence for any amount of nutritional intake (yes/no). The radiation oncology research nurse will oversee subject completion of these instruments.

MD Anderson Dysphagia Inventory (MDADI): The MDADI measures swallowing-related quality of life (QOL) in patients with swallowing dysfunction. It evaluates the patient's physical, emotional, and functional perceptions of swallowing dysfunction, and has been validated in head and neck cancer patients.

Performance Status Scale for Head and Neck Cancer Patients (PSS-H\&N): The PSS-H\&N is a clinician rated instrument consisting of three subscales: 1) normalcy of diet, 2) public eating, and 3) understandability of speech. The radiation oncology research nurse or speech-language pathologist will complete the PSS-H\&N.

Modified Barium Swallow (MBS) Study: Patients will undergo MBS testing at baseline, 4-6, 12, and 24 months after the completion of ART. Studies will be performed using standard radiographic systems with a videofluoroscope focused on the patient's lips anteriorly, the posterior pharyngeal wall posteriorly, the hard palate superiorly, and the upper esophageal segment inferiorly. The order of bolus presentation will include: two 5-ml Varibar thin liquid boluses, two 10-ml Varibar thin liquid boluses, two 20-ml Varibar thin liquid boluses, two cup sips of Varibar thin liquid, two pureed/Varibar pudding boluses, two solid boluses consisting of ¼ of a shortbread cookie or cracker coated with Varibar pudding, and 2 trials of the most difficult consistency in the A-P plane. The following measures will be used to quantify MBS findings: (1) Penetration-Aspiration Scale (PAS) - The PAS is a clinician rated 8-point, ordinal scale used to describe penetration and aspiration events. Scores are determined by depth of bolus invasion into the airway and the patient's response; a higher score is assumed to be a more severe sign of dysphagia. Intra- and interjudge reliability has been established in head and neck cancer patients. (2) Oropharyngeal swallow efficiency - (OPSE) is a global measure of swallow function defined as the ratio of the percent swallowed into the esophagus divided by oropharyngeal transit time. Thus, a higher OPSE score indicates a safer and more efficient oropharyngeal swallow. The continuous score obtained has been found to correlate with the degree of oropharyngeal dysphagia in head and neck cancer patients. (3) National Institutes of Health Swallowing Safety Scale (NIH-SSS) - The NIH-SSS provides a continuous numeric score to quantify swallowing safety using 7 dysphagia symptoms, residue, penetration, aspiration, response to aspiration, esophageal entry, regurgitation, and multiple swallows. The scale demonstrates high reliability (intra- and interrater intraclass correlation coefficient \>.95) and validity in dysphagic patients. We are concurrently evaluating its utility in patients with head and neck cancer. The speech pathologist will complete the PAS, OPSE, and NIH-SSS during analysis of the MBS study.

Salivary Flow Quantification: For unstimulated resting sialometry, each patient will be instructed to first clear the mouth by swallowing. With the head held slightly forward, the patient will be instructed not to swallow during the 5-minute collection, but to allow saliva to collect in the floor of mouth. The patient will expectorate the accumulated saliva into a pre-weighed 100 mL vial after 60 seconds. The patient will repeat this procedure 4 more times for a total collection time of 5 minutes. At the end of the 5 minutes, the collection vial will be promptly sealed and weighed. For each collection, the actual clock time at the start and end of the collection will be recorded as well as the vial weight before and after the collection of the sample. Stimulated sialometry will then be performed. Patients will rest for 5 minutes prior to collection. The exogenous stimulant will be 20 mL of citric acid solution held in the mouth for 1 minute. After the patient expectorates this solution, 5-minute saliva collection will take place as described above. These measurements will be done by the radiation oncology research nurse.

Study of Chemotherapy Prior to Radiotherapy and Chemotherapy in Patients With HPV Associated Cancer of the Oral Cavity

Phase II Trial of Neoadjuvant Chemotherapy for HPV-Associated Squamous Cell Carcinoma of the Oropharynx Followed by Reduced Dose Radiotherapy/Chemoradiotherapy for Responders or Standard Dose Chemoradiotherapy for Non-Responders

The 3-month response rate will be estimated using standard methods for estimating proportions and their 95% one-sided confidence intervals (CIs). Comparison to the historical control data will be carried out using a chi-square test for comparing proportions (or a Fisher exact test if an expected cell frequency in the 2x2 table is less than 5).

Zero (0) participants analyzed

To define objective tumor response rates to induction chemotherapy and to subsequent radiation-based treatment, per RESIST version 1.1 criteria.

assess Progression-free survival at 2 years.

To assess locoregional disease control at 2 years

3.5 To assess distant disease control at 2 years.

Serial evaluation of functional quality-of-life, including M. D. Anderson Dysphagia Inventory (MDADI) and Oropharyngeal swallowing efficiency (OPSE) measures of swallowing function, as well as formal sialometric measurement of parotid function.

To identify additional toxicity of treatment

Northwell Health

Serious and/or other \[non-serious\] adverse events were not collected/assessed due to premature termination of this study.

Patients treated with three cycles neoadjuvant chemotherapy who do not exhibit response to chemotherapy are then allocated to recieve standard dose and schedule radiotherapy.

chemotherapy: Chemotherapy for three cycles prior to radiotherapy

radiotherapy: Standard radiotherapy for non-responders vs reduced dose radiotherapy for responders.

Zero (0) participants analyzed

Chemotherapy Non-responders

Patients who respond to chemotherapy are treated with reduced dose radiotherapy.

chemotherapy: Chemotherapy for three cycles prior to radiotherapy

Reduced dose radiotherapy: Patients who achieve a response to chemotherapy then go on to receive reduced dose radiotherapy.

Zero (0) participants analyzed

Chemotherapy Responders

Patients treated with three cycles neoadjuvant chemotherapy who do not exhibit response to chemotherapy are then allocated to recieve standard dose and schedule radiotherapy.

chemotherapy: Chemotherapy for three cycles prior to radiotherapy

radiotherapy: Standard radiotherapy for non-responders vs reduced dose radiotherapy for responders.

Patients who respond to chemotherapy are treated with reduced dose radiotherapy.

chemotherapy: Chemotherapy for three cycles prior to radiotherapy

Reduced dose radiotherapy: Patients who achieve a response to chemotherapy then go on to receive reduced dose radiotherapy.

Total

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

data was not collected for Baseline Characteristics due to premature termination of this study

Study terminated , PI left the institution, no data analyzed

Jeffrey Revello Sr. Administrative Manager

Response (CR+PR) Status at 3 Months Post-therapy

No study intervention or data collected- Zero (0) participants analyzed

No Study Intervention or Data Collected- Zero (0) Participants

To Define Objective Tumor Response Rates to Induction Chemotherapy and to Subsequent Radiation-based Treatment.

Progression-free Survival at 2 Years

Assess Overall Survival at 2 Years.

Assess Locoregional Disease Control at 2 Years

Assess Distant Disease Control at 2 Years.

Assessment of Quality of Life Outcomes

Identify Additional Toxicity of Treatment

Overall Study

Musculoskeletal Diseases

Nervous System Diseases

Symptoms and General Pathology

Rare Diseases

Papilloma

Muscle Rigidity

Hypopharyngeal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Hypopharyngeal Cancer

Central Nervous System Depressants

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Chemotherapy Prior to Radiotherapy and Chemotherapy in Patients With HPV Associated Cancer of the Oral Cavity	NCT01525927	Oropharyngeal N...	chemotherapy radiotherapy Reduced dose ra...	18 Years -	Northwell Health
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

Spots Global Cancer Trial Database for neoplasms, oropharyngeal