Concurrent Hypofractionated Rth With Weekly Cisplatin in Locally Advanced SCCHN

• ClinicalTrials.gov Identifier: NCT03880396
• Recruitment Status: Unknown
• First Posted: March 19, 2019
• Last Update Posted: April 4, 2019
• Sponsor: Assiut University
• Information provided by (Responsible Party): Doaa Gamal Abdelnaser Fathy Mahmoud, Assiut University

Study Description

Brief Summary:

The primary endpoint will be acute toxicity. Secondary endpoints included: late toxicity and quality of life; loco-regional control, disease free survival and overall survival.

Condition or disease	Intervention/treatment	Phase
Squamous Cell Carcinoma of the Head and Neck	Radiation: hypofractionated Rth with platinol	Phase 2; Phase 3

Detailed Description:

Squamous cell carcinoma of head and neck (HNSCC) is being increasingly treated by multimodality approaches combining surgery, radiotherapy, and chemotherapy. Randomized controlled trials have demonstrated major improvements in loco-regional tumor control from altered fractionation radiotherapy with chemotherapy as compared with conventional fractionation.

Altered fractionation schedules seek to improve the therapeutic ratio between tumor cell kill and normal tissue damage by exploiting the dissociation between acute and late radiation effects. Hypofractionated radiotherapy utilizes a small number of fractions with a larger dose per fraction, shortening overall treatment time compared to a conventional protocol . Although a shorter treatment time can be obtained by applying a higher dose per fraction, it might also result in a disproportionate increase in the incidence of late complications.

In a meta-analysis of 50 trials including a total of 9615 patients, the addition of synchronous chemotherapy to radiotherapy for locally advanced SCCHN resulted in an overall survival benefit of 6.5% at five years . However, this is associated with late toxicity and questionable improvement in the therapeutic ratio Radiotherapy acceleration reduces the effect of tumor repopulation. Hypofractionated schedules accelerate treatment by employing fewer but larger radiation dose per fractions (>2Gy per fraction). In the meta analysis, treatment acceleration without total dose reduction (a category including eight trials and 3818 patients) increased five-year loco regional tumor control by 7.3%, but there was no overall survival benefit . Some schedules were associated with an unacceptable increase in acute toxicity and consequential late effects . This is partly due to the use of conventional 2D-planned radiotherapy and should be improved by application of highly conformed volumes, using intensity-modulated radiotherapy (IMRT) or 3Dconformal radiotherapy. In the meta-analysis, treatment acceleration with a reduction in the total dose did not improve loco regional tumor control . However, more than half of patients in this group received the CHART regimen (54 Gy in 36 fractions over 12 days), which can be criticised for an ' over shortening ' of the overall treatment time, where the relative onset of accelerated repopulation between normal mucosa (seven days) and tumor (21 days) was not fully exploited . For five fractions per week, the modeled optimal overall treatment time (to match early and late biologically equivalent doses to obtain greatest tumor effect) is in the range 20- 32 days (approx. 3- 5 weeks) The objective of this study was to investigate hypofractionated 3D CRT with 62.5 Gy in 25 daily fractions over five weeks (2.5 Gy per fractions biologically equivalent dose to the tumor, 70.9Gy 10 and late reacting tissues, 114.6 Gy 3) with synchronous weekly cisplatin 40mg/m2 in patients with stage III (T1-3 N1 or T3N0).And stage IVA,IVB (T1-4N2 orN3)

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Concurrent Hypofractionated Radiotherapy With Weekly Cisplatin in Locally Advanced Squamous Cell Carcinoma Head and Neck SCCHN
• Actual Study Start Date: March 10, 2019
• Estimated Primary Completion Date: December 10, 2019
• Estimated Study Completion Date: December 10, 2021

Arms and Interventions

Arm	Intervention/treatment
hypofractionated Rth with weekly cisplatin 40mg/m2; hypofractionated radioyherapy with weekly cisplatin 40mg/m2	Radiation: hypofractionated Rth with platinol; hypofractionated Rth with weekly cisplatin 40mg/m2

Outcome Measures

Primary Outcome Measures :

1. number of patients havingdegrees of Number of patients having acute toxicities of hypofractionated radiotherapy ,Number of patients with locoregional recurrence-free interval [ Time Frame: 96 week ]
   degree of acute toxicity (mucosititis degree) according to RECIST criteria,degree of dysphagia ,Number of patients with locoregional recurrence-free interval This is assessed by imaging studies and/or physical exams at follow- up visits. This will include a diagnostic FDG PET/CT scan. CT and/or MRI of the primary site and neck will also be recommended. Patients will be classified as locoregional recurrence-free as long as there is no evidence of locoregional recurrence of disease by clinical evaluation, CT, MRI, and/or PET-CT according to the standard of care. For patients achieving complete response of disease, no further imaging study is necessary.

Secondary Outcome Measures :

1. number of patients having degrees of late toxicities of chemoradiation, disease free survival interval,overall survival interval [ Time Frame: 2 years ]
   number of patients having late toxicity (grade's of xerostomia, dysphagia), disease free survival, overall survival accordind to RECIST criteria This is assessed by imaging studies and/or physical exams at follow- up visits. This will include a diagnostic FDG PET/CT scan. CT and/or MRI of the primary site and neck will also be recommended. Patients will be classified as disease-free survival as long as there is no evidence of locoregional recurrence of disease by clinical evaluation, CT, MRI, and/or PET-CT according to the standard of care. For patients achieving complete response of disease, no further imaging study is necessary.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Have histologically or cytologically proven oropharyngeal, laryngeal or hypopharyngeal squamous cell carcinoma; with AJCC high risk stage II (T2N0, excluding glottic laryngeal) disease, stage III (T1-3N1 or T3N0) and stage IV (T1-4N2 or N3) Locally advanced non metastatic stage II/IV SCCHN according to AJCC stage classification 2018 (8th edition);
• Age >18 years and <75 years;
• No previous treatment(neither chemotherapy nor radiotherapy);
• Eastern Cooperative Oncology Group(ECOG) performance status of <2;
• Adequate organ function;
• Provide informed oral or written consent.

Exclusion Criteria:

• prior surgical curative resection for primary tumor;
• patients with metastatic disease;
• prior radiotherapy within the treatment field;
• any relative contraindication to radiotherapy;
• prior administration of EGFR monoclonal antibodies, signal transduction inhibitors or targeted therapies;
• Active severe infection;
• Active concomitant malignancy;
• Pregnant and or lactating women;
• Pre-existing motor or sensory neurotoxicity > WHO grade 2.

Contacts and Locations

Locations

Egypt

Assiut university

Assiut, Egypt, +2

Sponsors and Collaborators

Assiut University

Investigators

• Principal Investigator: Doaa G Abdelnaser Fathy Mahmoud, Doctor; Assiut University
• Principal Investigator: Hoda H Essa, Doctor; Assiut University
• Principal Investigator: Ola N Abdelfatah, Doctor; Assiut University
• Principal Investigator: Aiat M Mohammed, Doctor; Assiut University
• Principal Investigator: Mohamed O Gad, Doctor; Assiut University

More Information

Publications:

Thomson DJ, Ho KF, Ashcroft L, Denton K, Betts G, Mais KL, Garcez K, Yap BK, Lee LW, Sykes AJ, Rowbottom CG, Slevin NJ. Dose intensified hypofractionated intensity-modulated radiotherapy with synchronous cetuximab for intermediate stage head and neck squamous cell carcinoma. Acta Oncol. 2015 Jan;54(1):88-98. doi: 10.3109/0284186X.2014.958528. Epub 2014 Oct 3.

Szutkowski Z, Kawecki A, Jarząbski A, Laskus Z, Krajewski R, Michalski W, Kukołowicz P. Hypofractionated accelerated radiotherapy in T1-3 N0 cancer of the larynx: A prospective cohort study with historical controls. Rep Pract Oncol Radiother. 2016 Nov-Dec;21(6):537-543. Epub 2016 Sep 20.

• Responsible Party: Doaa Gamal Abdelnaser Fathy Mahmoud, Principle investigator, Assiut University
• ClinicalTrials.gov Identifier: NCT03880396
• Other Study ID Numbers: chemoradiation in SCCHN
• First Posted: March 19, 2019
• Last Update Posted: April 4, 2019
• Last Verified: April 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Neoplasms by Site; Cisplatin; Antineoplastic Agents