HYpofractionateD RadioAblative (HYDRA) Treatment of Advanced Laryngeal Cancer (HYDRA)

A Phase I Trial of Stereotactic HYpofractionateD RadioAblative (HYDRA) Treatment of Advanced Laryngeal Cancer

single-modality phase I dose escalation toxicity study for first-line curative treatment of head and neck squamous cell carcinoma.

Study Overview

• Status: Terminated
• Conditions: Squamous Cell Carcinoma of the Larynx
• Intervention / Treatment: Radiation: radiation

Detailed Description

HYDRA will consist of 5 fraction SBRT treatment targeting only grossly evident disease localized by examination and standard diagnostic CT, MR, and PET-CT imaging. Prophylactic coverage of uninvolved at-risk mucosal and nodal drainage basins will be strictly disallowed. The initial dose cohort will be treated to a total of 42.5 Gy in five equal fractions delivered every other day over a two week period (biologically equivalent to 66 Gy delivered in 2 Gy daily fractions), drawn from our successful institutional experience with similar dosing and fractionation for early-stage larynx SBRT. Escalation of total dose will proceed in 2.5 Gy increments, up to a final target dose of 50 Gy.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients older than 18 years of age with histologically proven squamous cell carcinoma of the larynx.
• Stage T1-2N1-2c/T3-4N0-2c disease, as defined by American Joint Committee on Cancer (AJCC) criteria.
• ECOG (Zubrod) performance status 0-2.
• Must be functionally and technically fit for partial laryngectomy.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.
• Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

• Patients who have undergone resection of primary disease.
• Patients who have received induction chemotherapy for their cancer diagnosis.
• Patients who have undergone a diverting tracheostomy which is either a) traversing directly through tumor, b) has been placed for true airway insufficiency. Patients with a tracheostomy placed preemptively for impending airway compromise remain eligible for enrollment.
• Prior cancer diagnosis, except appropriately treated localized epithelial skin cancer or cervical cancer.
• Prior radiation therapy to the head and neck region.
• Women of childbearing potential (a woman of child-bearing potential is a reproductively mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months [i.e., who has had menses at any time in the preceding 24 consecutive months]) and male participants must practice effective contraception (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study.
• Patients unable or unwilling to give written, informed consent.

• Severe, active co-morbidity, defined as follows:

  1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months.
  2. Transmural myocardial infarction within the last 6 months.
  3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
  4. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration.
  5. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol.
  6. Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. Protocol-specific requirements may also exclude immuno-compromised patients.
  7. History of treatment with potent immunosuppressive drugs for such conditions as post organ transplant, severe rheumatoid arthritis, etc. within the past 6 months.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
• Evidence of metastatic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiation; Patients in each dose cohort will all be treated as a single group. The starting dose will be 8.5 Gy per fraction for 5 fractions (total dose = 42.5 Gy). Subsequent cohorts of patients will receive an additional 0.5 Gy per fraction.	Radiation: radiation; Patients in each dose cohort will all be treated as a single group. The starting dose will be 8.5 Gy per fraction for 5 fractions (total dose = 42.5 Gy). Subsequent cohorts of patients will receive an additional 0.5 Gy per fraction.; Other Names: HYpofractionateD RadioAblative

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
toxicities	Number of participants with acute related serious adverse events	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events	Number of participants with adverse events	2 years
quality of life	Scale of quality of life questionnaire	5 years
disease control	Number of participants with disease control (no evidence of disease, progression)	5 years
dosimetric improvement	Scores of radiation quality review	2 weeks

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Lucien Nedzi, MD, UTSW Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2015
• Primary Completion (Actual): March 4, 2019
• Study Completion (Actual): March 4, 2019

Study Registration Dates

• First Submitted: May 7, 2015
• First Submitted That Met QC Criteria: June 2, 2015
• First Posted (Estimate): June 8, 2015

Study Record Updates

• Last Update Posted (Actual): August 20, 2020
• Last Update Submitted That Met QC Criteria: August 19, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Otorhinolaryngologic Diseases; Carcinoma, Squamous Cell; Laryngeal Diseases; Squamous Cell Carcinoma of Head and Neck; Laryngeal Neoplasms
• Other Study ID Numbers: STU 052014-085