Clinical trial NCT03388931: Radiotherapy Dose Escalation in Locally Advanced Squamous Cell Carcinoma of the Larynx or Hypopharynx
Official title: Radiotherapy Dose Escalation in Locally Advanced Squamous Cell Carcinoma of the Larynx or Hypopharynx
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Advanced Squamous Cell Carcinoma
Keywords: Radiotherapy Dose Escalation
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2018-01-03
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase 2 single arm study of a novel schedule of hyperfractionated radiotherapy (RT) in combination with our standard chemotherapy program for patients with stage 3-4 squamous cell carcinoma of the larynx. The primary hypothesis of our study is that the study program will improve Laryngectomy-Free Survival compared to historical controls. The study is limited to patients who would be receiving primary RT-C as standard therapy off-study.

Detailed description: The novel radiotherapy schedule that is the subject of this study is only slightly different from the program that has been used in the cooperative group trial RTOG 9003. The radiation therapy dose schedule in our study twice-daily alternating fractions over 30 treatment days. The Biologically Effective Dose (BED) of this schedule is about 11% higher than our standard schedule twice-a-day. During radiotherapy, patients will receive chemotherapy with our standard program of weekly.

Eligibility criteria: Inclusion Criteria:

* At least 18 years of age (no upper age limit)
* Biopsy proven squamous cell carcinoma of the glottis or supraglottic larynx or hypopharynx with the following T,N and M stages:
* Glottic Larynx:

T3-4: Any primary tumor volume

* Supraglottic Larynx:

T2: Primary tumor volume \> 4.0cc T3-4: Any primary tumor volume

* Hypopharynx:

T2: Primary tumor volume \> 4.0cc T3-4: Any primary tumor volume

* N-Stages (the same for all primary sites): All N-stages
* M-Stages (the same for all primary sites): M0 or M1suitable for curative attempt with Stereotactic Body Radiation Therapy.
* Radiologic evaluation of the chest within 12 weeks prior to treatment; at a minimum, chest x-ray is required. CT imaging of the chest or PET/CT is acceptable.
* ECOG Performance Status 0-2
* CBC/differential obtained within 8 weeks prior to treatment, with adequate bone marrow function defined as follows:
* Platelets ≥ 100,000 cells/mm3
* Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
* Adequate renal and hepatic function within 4 weeks prior to treatment, defined as follows:
* Serum creatinine \< 2.0 mg/dl
* Total bilirubin \< 2 x the institutional ULN
* AST or ALT \< 3 x the institutional ULN.

  \*Note that physician attestation of patient having no known history of liver disease can take the place of bilirubin and AST/ALT labs.
* Negative pregnancy test within 2 weeks prior to treatment for women of childbearing potential
* Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment.
* Patients must be deemed able to comply with the treatment plan and follow-up schedule.
* Patients must provide study specific informed consent prior to study entry

Exclusion Criteria:

* Prior history of radiation therapy to the head and neck that would likely increase the risk of serious complications from the RT delivered on this protocol
* Prior history of head and neck cancer with the exception of nonmelanoma skin cancer.
* Currently taking Disease Modifying Rheumatoid Drugs (DMRDs)
* Severe, active co-morbidity, defined as follows:
* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
* Transmural myocardial infarction within the last 6 months
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
* Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; Note, however, coagulation parameters are not required for entry into this protocol.
* Pre-existing ≥ grade 2 neuropathy
* Prior organ transplant
* Systemic lupus
* Psoriatic arthritis.
* Known HIV positive. HIV positive patients are known to have worse clinical outcomes especially for local, regional, and distant cancer control. This poorer prognosis is thought to be secondary to a compromised immune system.

Primary outcomes:
measure: Whether radiation therapy dose escalation as used in our study will improve Laryngectomy-Free Survival compared to historical controls in patients with locally advanced squamous cell carcinoma of the larynx.
timeFrame: Up to 2 years
Secondary outcomes:
measure: Patient reported quality of life
timeFrame: Up to 2 years
measure: Psychosocial function
timeFrame: Up to 2 years
measure: Swallowing ability.
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Robert J Amdur, MD
role: PRINCIPAL_INVESTIGATOR
References: