Neoplasms

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Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Stomatognathic Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

To prospectively assess post-radiation late dysphagia by using MDADI questionnaire (deglutition-related quality of life) and objective instrumental assessment by means of Fiberoptic Endoscopic Evaluation of Swallowing (FEES) and Videofluoroscopy (VFS) in patients affected by nasopharynx and oropharynx cancers candidates to radiochemotherapy. Radiotherapy is delivered by using Intensity and Modulated Technique (IMRT) with a planning dose optimization to the swallowing related structures (SWOARs-sparing IMRT).

The primary aim is to assess the variations of MDADI, FEES and VFS from baseline to 6 and 12 months after treatment.

The secondary aim is to correlate clinical and instrumental results as well as radiation dose received by the different swallowing related structures (SWOARs) to the variations of clinical (MDADI) and instrumental (FEES and VFS) scores.

The aim of the study is to prospectively investigate the impact of radiochemotherapy on both the deglution-related quality of life (QoL) by means of MDADI questionnaire and the swallowing function by means of Fiberoptic Endoscopic Evaluation of Swallowing (FEES) and Videofluoroscopy (VFS).

Radiotherapy All patients requiring bilateral neck irradiation will be considered.

The clinical target volumes (CTVs) is directly delineated by the radiation oncologist according to the guidelines of the Italian Association of Radiation Oncology-Head and Neck Working Group 27 and the corresponding planning target volumes (PTVs) is automatically created by uniform expansions of 0.3 cm.

Patients positioning is assessed by weekly cone beam CT (CBCT) and online correction to reduce systematic set-up errors.

The prescribed doses is 66 Gy at 2.2 Gy per fraction to the high risk gross volume PTV and 60-54 Gy at 2.0-1.8 Gy per fraction to the intermediate (optional) and low risk subclinical PTVs, respectively, delivered concomitantly in 30 daily fractions.

Eight different SWOARs are defined in each CT slice and included in IMRT planning objective functions: superior, middle and inferior constrictor muscle (SPCM, MPCM and IPCM), supraglottic larynx (SL), glottis larynx (GL), cricopharyngeus muscle (CPM) and cervical oesophagus (CE). Thereafter, the mean dose received by each swallowing structures as well as by parotid glands and oral cavity will be recorded.

In the IMRT optimisation cost function, target coverage replace sparing of any SWOARs, parotid glands and oral cavity, but the spinal cord.

The IMRT plans set target prescription goals and spinal cord maximum dose (Dmax) as the highest priority, whereas SWOAR constraints are set as secondary.

Medical therapy

Chemotherapy is given weekly using Cisplatin 40 mg/mq for a maximum of 6 cycles or 100 mg/mq every 3 weeks during the 6-week RT course for a maximum of 3 cycles.

MDADI questionnaire

All the enrolled patients fill in the MDADI questionnaire at baseline and at 6 and 12 months after ChemoRT. The validated Italian version of MDADI is used. A MDADI score of at least 80 represents an "optimal" deglutition-related QoL, a score between 60 and 80 represents an "adequate" deglutition-related QoL, and a score less than 60 represents a "poor" deglutition-related QoL. A 10-point difference in the MDADI composite score is considered a minimal clinically important difference (MCID) in the deglutition-related QoL.

Fiberoptic Endoscopic Evaluation of Swallowing (FEES)

This exam is specifically used to evaluate the severity of post-swallowing pharyngeal residue according to Farneti pooling score (P-score), a reliable and validated tool that significantly predicts aspirations.

Videofluoroscopy (VFS)

This exam is specifically used to evaluate the pattern of penetration and aspiration based on the Penetration-Aspiration Scale (PAS)

Dysphagia Assessment After Swallowing Sparing RadioTherapy

Clinical and Instrumental Evaluation of Late Dysphagia in Naso and Oropharynx Cancer After Swallowing-organs (SWOARs)-Sparing Chemo-IMRT

All patients will be evaluated by using MDADI questionnaire at baseline and at 6 and 12 months after radiochemotherapy. The variations of MDADI questionnaire scores from before to after treatment will be analysed.

All patients will be evaluated by using FEES at baseline and at 6 and 12 months after radiochemotherapy. The variations of FEES scores from before to after treatment will be analysed

All patients will be evaluated by using VFS at baseline and at 6 and 12 months after radiochemotherapy. The variations of VFS scores from before to after treatment will be analysed

The correlation between clinical (MDADI) and instrumental (FEES and VFS) scores will be performed according to the following dichotomy:

MDADI \>80 vs MDADI \<80 (optimal vs adequate or poor) FEES P-score 4-7 vs 8-11 (no/mild dysphagia vs adequate/severe dysphagia) VFS PAS score 1-2 vs 3-8 (safe deglutition vs penetration or aspiration)

Correlation between MDADI, FEES and VFS score changes with radiation dose received by the SWOARs will be performed according to the following criteria.

The following radiation dose features (Gy) will be extracted for each SWOAR from dose volume hystograms (DVHs): V35, V45, V55, V65, minimum dose (Dmin), maximum dose (Dmax), mean dose (Dmean) and the dose corresponding to the absolute maximum of the differential DVH, hence the modal dose (Dmp).

The abovementioned dose features will be correlated with the following outcome measures and according to the following stratification criteria:

MDADI \>80 vs MDADI \<80 (optimal vs adequate or poor) FEES P-score 4-7 vs 8-11 (no/mild dysphagia vs adequate/severe dysphagia) VFS PAS score 1-2 vs 3-8 (safe deglutition vs penetration or aspiration)

Azienda Ospedaliero, Universitaria Pisana

Researcher

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Squamous Cell

Laryngeal Diseases

Neoplasms, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Hypopharyngeal Neoplasms

Laryngeal Cancer

Hypopharyngeal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

* Participants will be enrolled in cohorts of 3- 6 per dose level. Once the MTD is reached, an additional 10 patients will be treated at that dose level and an amendment will be submitted to declare the dose.
* BKM120 will start 2 weeks prior to first dose of cisplatin and radiation start. During the study, BKM120 will be administered orally daily for 45 days. Starting dose 40 mg.
* Cisplatin: Starting Dose 30 mg/m2, given IV, weekly on days: (1, 8, 15, 22, 29, 36 and 43).
* Radiotherapy: All participants will receive daily radiotherapy with intensity-modulated radiotherapy (IMRT) for 7 weeks.

BKM120 is a potent and highly specific oral pan-class I PI3K inhibitor.

BKM120

IMRT is the medical use of ionizing radiation, generally as part of cancer treatment to control or kill malignant cells

Intensity-modulated radiotherapy (IMRT)

Glenn J. Hanna, MD

This research study is evaluating a drug called buparlisib (BKM120) as a possible treatment for locally advanced head and neck squamous cell cancer.

* This phase Ib study is combining standard chemoradiotherapy with weekly cisplatin and BKM120 to assess tolerability of this combination in high risk patients with locally advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN). The investigators will also obtain preliminary information about the efficacy of this treatment.
* The participant will receive the study drug buparlisib once daily, by mouth, for 45 days. The participant will be given a study drug-dosing diary for each cycle. It will include special instructions for taking the study drug at home.
* The investigators are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects, not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study before and how well they have tolerated their doses.
* All participants will receive weekly cisplatin injection. Cisplatin will be given intra-venously (IV) on days: (1, 8, 15, 22, 29, 36 and 43) at DFCI.
* All participants will receive daily radiotherapy with intensity-modulated radiotherapy (IMRT) for 7 weeks, delivered at DFCI. IMRT is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor.
* The investigators would like to keep track of the participant's medical condition. Follow-up will continue every 4 to 12 weeks after the end of treatment for the first year and at the investigator's discretion thereafter.

Phase Ib Study of BKM120 With Cisplatin and XRT in High Risk Locally Advanced Squamous Cell Cancer of Head and Neck

A Phase Ib Study of BKM120 With Weekly Cisplatin and Radiotherapy in High Risk Locally Advanced Squamous Cell Cancer of the Head and Neck

There are no plans to share the IPD. Cumulative data will be published however.

Determine Maximum Tolerated Dose (MTD) of BKM120/cisplatin in combination with radiation therapy in patients with locally advanced squamous cell cancer of the head and neck.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Dysphagia Assessment After Swallowing Sparing RadioTherapy	NCT03448341	Cancer of Oroph... Cancer of Nasop...		18 Years - 80 Years	Azienda Ospedaliero, Universitaria Pisana
Phase Ib Study of BKM120 With Cisplatin and XRT in High Risk Locally Advanced Squamous Cell Cancer of Head and Neck	NCT02113878	Carcinoma, Squa... HPV Positive Or... Hypopharyngeal ... Early Invasive ... Carcinoma of La... Cancer of Nasop...	BKM120 Cisplatin Intensity-modul...	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for cancer of nasopharynx