Intensity Modulated Proton Therapy After Surgery for the Treatment of Head and Neck Cancer, the HEADLIGHT Study

Brief Title

Intensity Modulated Proton Therapy After Surgery for the Treatment of Head and Neck Cancer, the HEADLIGHT Study

Official Title

HEADLIGHT: Hypofractionated Proton Therapy for Head and Neck Cancers

Brief Summary

      This clinical trial tests whether intensity modulated proton therapy after surgery works to
      shrink tumors in patients with head and neck cancer. Radiation therapy uses high energy
      protons to kill tumor cells and shrink tumors.
    

Detailed Description

      PRIMARY OBJECTIVE:

      I. The primary goal is to evaluate the local-regional control among subjects in both arms at
      2 years after study registration.

      SECONDARY OBJECTIVES:

      I. To determine overall survival progression free survival local, regional, distant
      recurrence risks, and infield and outfield recurrence in the trial at 2 years after study
      registration.

      II. To determine the rate and duration of grade 3+ acute adverse events from treatment start
      to 30 days after radiation completion date).

      III. To determine the incidence of secondary acute effects attributable to radiotherapy (e.g.
      percutaneous endoscopic gastrostomy [PEG] tube placement, duration and dose of narcotic
      analgesia required, weight loss, and hospitalization days).

      IV. To determine the impact of treatment on patient reported quality of life. V. To
      objectively quantify the severity of oral mucositis during and following radiotherapy.

      EXPLORATORY OBJECTIVES:

      I. To estimate direct and indirect costs of the study regimen and compare these with standard
      of care treatment techniques.

      II. To correlate histopathologic, molecular, and tumor genetic/epigenetic alterations with
      clinical outcomes.

      III. To correlate circulating biomarkers (microribonucleic acid [miRNA], circulating tumor
      deoxyribonucleic acid [ctDNA]) with clinical outcomes.

      IV. To determine adverse events and patient reported outcomes related to abbreviated
      concomitant chemotherapy.

      V. To determine incidence and severity of late effects attributable to radiotherapy at 1-3
      years after treatment.

      VI. To qualitatively evaluate patient beliefs regarding tradeoffs of cancer control,
      treatment time, cost, acute side effects, and late side effects.

      VII. To determine cancer out comes, adverse events, and patient reported outcomes and compare
      across head and neck subsites, between those aged 65 to those age < 65 at date of enrollment,
      between male and female, and in the adjuvant population between time to total package
      completion (< 9 weeks vs weeks, surgery day 0) and by treatment with and without
      chemotherapy.

      VIII. To evaluate the predictive relationship of linear energy transfer (LET) weighted
      modeling using an relative biologic enhancement (RBE) based model and RBE independent model
      with grade 3+ acute and late toxicity.

      OUTLINE: Patients are assigned to 1 of 2 arms.

      ARM A: Patients who already underwent surgical resection undergo intensity modulated proton
      therapy (IMPT) for 18 sessions (Monday-Friday) over 24 days in the absence of disease
      progression or unacceptable toxicity. Patients may receive cisplatin intravenously (IV) over
      1-2 hours per standard of care.

      ARM B: Patients undergo surgical resection and then IMPT for 15 sessions (Monday-Friday) over
      19 days in the absence of disease progression or unacceptable toxicity. Patients may receive
      cisplatin IV over 1-2 hours per standard of care.

      After completion of study treatment, patients are followed up within 21 days, every 3 months
      for 2 years, and then every 6-12 months for 5-10 years.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Rate of local/regional control (LRF)

Secondary Outcome

 Incidence of acute adverse events

Condition

Head and Neck Carcinoma

Intervention

Cisplatin

Study Arms / Comparison Groups

 Arm A (IMPT, cisplatin)
Description:  Patients who already underwent surgical resection undergo IMPT for 18 sessions (Monday-Friday) over 24 days in the absence of disease progression or unacceptable toxicity. Patients may receive cisplatin IV over 1-2 hours per standard of care.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

117

Start Date

December 15, 2021

Completion Date

November 15, 2026

Primary Completion Date

November 15, 2025

Eligibility Criteria

        Inclusion Criteria:

          -  Age >= 18 years

          -  Histological confirmation of a newly diagnosed non-human papillomavirus (HPV)
             associated malignant epithelial cancer in the head and/or neck. Diagnosis requires
             confirmation of p16 and/or HPV DNA negativity for oropharyngeal and unknown primary
             sites. p16 positivity in skin cancers is allowed

          -  Primary lesion located in the nasal cavity, paranasal sinuses, oral cavity,
             oropharynx, larynx, hypopharynx, salivary glands, lymph nodes (unknown primary or
             metastasis from head and neck [HN]-skin primary) or skin cancer where lymph node
             radiation is recommended

               -  NOTE: Patients with primary lesions in the larynx must have a T3 primary, bulky
                  T2 primary (> 6 cc), and/or at least 1 regional lymph node

          -  Confirmation of American Joint Committee on Cancer (AJCC) 8th edition defined M0
             established by positron emission tomography (PET)/computed tomography (CT) or
             PET/magnetic resonance imaging (MRI)

          -  Eastern Cooperative Oncology Group (ECOG) performance status (0-1 prior to initial
             treatment)

          -  Able to provide written informed consent

          -  Able to complete questionnaires independently or with assistance

          -  Willing to return to enrolling institution for follow up during the observation phase

          -  Hemoglobin >= 8.0 g/dl (within 8 weeks of registration)

          -  Platelets >= 75,000 cells/mm^3 (within 8 weeks of registration)

          -  Absolute neutrophil count > 1500 cells/mm^3 (within 8 weeks of registration)

          -  Coronavirus disease 2019 (Covid-19) testing per institutional standard. If
             pre-treatment testing, patients should be negative prior to starting treatment or
             symptom free for at least 14 days from documented positive test. Vaccination status
             should be documented

        Exclusion Criteria:

          -  Pregnant women (serum pregnancy test required before treatment per department policy)

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
             positive and currently receiving antiretroviral therapy

               -  NOTE: Patients known to be HIV positive, but without clinical evidence of
                  immunocompromised state, are eligible for this trial

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm

          -  Other active malignancy =< 2 years prior to registration

               -  EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix and
                  prostate cancer with a Gleason score of 6 or less

               -  NOTE: If there is a history or prior malignancy, they must not be receiving
                  ongoing anticancer treatment

          -  History of myocardial infarction =< 6 months, or congestive heart failure requiring
             use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

          -  Prior radiation therapy that would have a clinically significant overlap with the
             intended head/neck radiation

          -  Unable to receive proton therapy because of extensive metallic hardware in close
             proximity to treatment site, logistical circumstances, or any other reason

          -  Any of the following diagnoses: HPV-associated squamous cell carcinoma, germ cell
             tumors, hematologic malignancies, neuroendocrine malignancies, adenoid cystic
             carcinoma, sarcomas of bone, benign tumors
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Scott C Lester, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT05075980

Organization ID

GMROR2171

Secondary IDs

NCI-2021-09706

Responsible Party

Sponsor

Study Sponsor

Mayo Clinic

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Scott C Lester, Principal Investigator, Mayo Clinic in Rochester


Verification Date

November 2021