QUantitative Assessment of Swallowing After Radiation (QUASAR)

Head and Neck Cancer Clinical Trial

— QUASAR  

Official title:

QUantitative Assessment of Swallowing After Radiation (QUASAR): A Longitudinal Comparison of Swallowing Function by Systemic Therapy in Head and Neck Cancer Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04359199
• Other study ID #: 190048
• Status: Recruiting
• Start date: September 1, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2023
• Source: University of California, San Diego
• Contact: Khusbu Singh, MBBS, CCRP
• Phone: 858-245-2604
• Email: ksingh[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To use novel methods for quantitative analysis of VFSS (videofluoroscopic swallow study, also known as modified barium swallow) to study and compare dysphagia in patients treated for head and neck carcinoma with concurrent radiation therapy and chemotherapy (cisplatin) or targeted therapy (cetuximab) vs. immunotherapy (pembrolizumab, nivolumab, or durvalumab). Our hypothesis is that pharyngeal constriction will be greater (lower ratio) with concurrent immunotherapy compared to chemotherapy, as measured by the pharyngeal constriction ratio (PCR).

Description:

The QUASAR study will use a prospective, observational, cross sectional design (See Schema). HNC patients treated with definitive RT and immunotherapy or chemotherapy (cetuximab or cisplatin) will undergo VFSS at 4-6 and 12-24 months post-treatment. Patients enrolled prior to 6 months after finishing therapy will undergo a swallow study during the 4-6 month period AND the 12-24 month period. Patients enrolled after 6 months after finishing therapy will undergo a single swallow study in the 12-24 month period. The primary endpoint of PCR at 12-24 months will be compared between patients treated with immunotherapy versus chemotherapy. All patients with HNC treated with definitive RT and systemic therapy at our institution will be eligible. In particular, we will recruit patients for this study from participants in two ongoing trials investigating the use of concurrent immunotherapy. The KEYCHAIN trial (ClinicalTrials.gov Identifier: NCT03383094) randomizes patients with locally advanced p16+ HNC undergoing definitive RT to concurrent q3 week cisplatin versus concurrent and adjuvant pembrolizumab. NRG-HN004 (ClinicalTrials.gov Identifier: NCT03258554) is a cooperative group trial that compares HNC patients that are not eligible for cisplatin undergoing definitive radiation therapy to concurrent cetuximab versus durvalumab.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Biopsy-proven, un-resected invasive carcinoma of the head and neck.
• Treated with definitive RT and concurrent systemic therapy or treated within the past 4-24 months
• Concurrent systemic therapy with Cisplatin, Cetuximab or immunotherapy.
• Age = 18
• Able to understand and willing to sign a written informed consent.

Exclusion Criteria:

• Prior radiotherapy that would result in overlap of planned radiation therapy fields.
• Prior systemic chemotherapy, unless as part of the coordinated plan of care for the treatment of the carcinoma (e.g., induction/neoadjuvant chemotherapy is allowed)
• Planned adjuvant (i.e., following definitive chemoradiotherapy) chemotherapy or surgery

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Deglutition Disorders
• Dysphagia
• Head and Neck Cancer
• Head and Neck Neoplasms
• Oropharyngeal Dysphagia
• Oropharyngeal Neoplasms
• Oropharynx Cancer
• Oropharynx Squamous Cell Carcinoma

Intervention

Radiation:
• Radiation Therapy
Routine radiation dosing (approximately 70 Gy in 35 fractions over 6.5 weeks) to the head and neck for the treatment of head and neck cancer

Drug:
• Cetuximab
Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor used for the treatment of head and neck cancer
• Chemotherapy
Cisplatin is a chemotherapy medication used to treat a number of cancers, including head and neck cancer
• Immunotherapy
Keytruda or Pembrolizumab is a highly selective humanized monoclonal IgG4 antibody directed against the PD-1 receptor on the cell surface. Opdivo or Nivolumab is a targeted therapy. It is a human programmed death receptor-1 (PD-1) blocking antibody. Imfinzi or Durvalumab is an anti-cancer ("antineoplastic") drug. This medication is classified as an Anti-PD-L1 monoclonal antibody.

Locations

Country	Name	City	State
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	UCSD Moores Cancer Center	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
Loren Mell, MD

Country where clinical trial is conducted

United States, 

References & Publications (11)

Basch E, Iasonos A, McDonough T, Barz A, Culkin A, Kris MG, Scher HI, Schrag D. Patient versus clinician symptom reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events: results of a questionnaire-based study. Lancet Oncol. 2006 Nov;7(11):903-9. doi: 10.1016/S1470-2045(06)70910-X. — View Citation

Duprez F, Madani I, De Potter B, Boterberg T, De Neve W. Systematic review of dose--volume correlates for structures related to late swallowing disturbances after radiotherapy for head and neck cancer. Dysphagia. 2013 Sep;28(3):337-49. doi: 10.1007/s00455-013-9452-2. Epub 2013 Feb 22. — View Citation

Green G, Kim E, Carmona R, Shen H, Murphy JD, Mell LK. Incidence of Long-Term Esophageal Dilation With Various Treatment Approaches in the Older Head and Neck Cancer Population. Front Oncol. 2018 Oct 23;8:466. doi: 10.3389/fonc.2018.00466. eCollection 201 — View Citation

Jensen K, Lambertsen K, Grau C. Late swallowing dysfunction and dysphagia after radiotherapy for pharynx cancer: frequency, intensity and correlation with dose and volume parameters. Radiother Oncol. 2007 Oct;85(1):74-82. doi: 10.1016/j.radonc.2007.06.004. Epub 2007 Jul 27. — View Citation

Leonard R, Kendall K. Dysphagia Assessment and Treatment Planning: A Team Approach. Fourth. Plural Publishing; 2018

Leonard R, Rees CJ, Belafsky P, Allen J. Fluoroscopic surrogate for pharyngeal strength: the pharyngeal constriction ratio (PCR). Dysphagia. 2011 Mar;26(1):13-7. doi: 10.1007/s00455-009-9258-4. Epub 2009 Oct 24. — View Citation

Liang Y, Messer K, Rose BS, Lewis JH, Jiang SB, Yashar CM, Mundt AJ, Mell LK. Impact of bone marrow radiation dose on acute hematologic toxicity in cervical cancer: principal component analysis on high dimensional data. Int J Radiat Oncol Biol Phys. 2010 Nov 1;78(3):912-9. doi: 10.1016/j.ijrobp.2009.11.062. Epub 2010 May 14. — View Citation

Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, Postow MA, Wolchok JD. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015 Dec;26(12):2375-91. doi: 10.1093/annonc/mdv383. Epub 2015 Sep 14. Erratum In: Ann Oncol. 2016 Jul;27(7):1362. — View Citation

Servagi-Vernat S, Ali D, Roubieu C, Durdux C, Laccourreye O, Giraud P. Dysphagia after radiotherapy: state of the art and prevention. Eur Ann Otorhinolaryngol Head Neck Dis. 2015 Feb;132(1):25-9. doi: 10.1016/j.anorl.2013.09.006. Epub 2014 Jun 9. — View Citation

Stoeckli SJ, Huisman TA, Seifert B, Martin-Harris BJ. Interrater reliability of videofluoroscopic swallow evaluation. Dysphagia. 2003 Winter;18(1):53-7. doi: 10.1007/s00455-002-0085-0. — View Citation

Yip H, Leonard R, Belafsky PC. Can a fluoroscopic estimation of pharyngeal constriction predict aspiration? Otolaryngol Head Neck Surg. 2006 Aug;135(2):215-7. doi: 10.1016/j.otohns.2006.03.016. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Swallowing function 12-24 months after concurrent radiation and systemic therapy for HNC, as measured by the PCR	will use a two-sample t-test at 0.05 level to compare Pharyngeal Constriction Ratio (PCR) between groups	12-24 months
Secondary	Quantitative swallowing function at 4-6 months and 12-24 months by PCR, TPT, PRR and PPWT	To compare swallowing function between systemic therapies with additional quantitative metrics of swallowing dysfunction from the VFSS including TPT, PRR and PPWT.; The presence of aspiration or strictures on VFSS will be compared as binary variables between groups using Pearson's Chi squared test.	4-6 months and 12-24 months
Secondary	Correlation between quantitative swallowing function and patient reported symptoms using the EAT-10 tool	To compare patient reported assessments of swallowing function with the EAT-10 tool between systemic therapies.; To test if there is correlation between the quantitative VFSS metrics and patient reported outcomes on the EAT-10 index, we will calculate Pearson's correlation coefficient and plot the results on a correlation matrix. The Holm step down procedure will be used to adjust for multiple testing to control the family-wise error rate at 0.05 level.	12-24 months
Secondary	Correlation between radiation dose and location of swallowing function and quantitative swallowing function	The purpose of this aim is to evaluate the effect of radiation dose on swallowing structures, applying a previously developed space-preserving NTCP approach based on principal component analysis (PCA).; Using this approach, dose distributions to the global swallowing apparatus (i.e. pharynx, larynx and esophagus) will be standardized for patients from both arms of Aim 1, using deformable registration to standardize organs and 3-D dose distributions to a common template. Dose distributions will be converted into a dose array and PCA will be applied to the dose array, as previously described. We will then use PC linear regression to identify eigenvectors significantly associated with long term dysphagia (as measured by PCR).	24 months