Clinical trial NCT04870840: Image-guided Proton Therapy for the Treatment of Locally Advanced Unresectable Head and Neck Cancer
Official title: Proton Image-Guided Radiation Assignment for Therapeutic Escalation Via Selection of Locally Advanced Head and Neck Cancer Patients [PIRATES]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced Head and Neck Squamous Cell Carcinoma
Locally Advanced Hypopharyngeal Squamous Cell Carcinoma
Locally Advanced Laryngeal Squamous Cell Carcinoma
Locally Advanced Nasopharyngeal Squamous Cell Carcinoma
Locally Advanced Oral Cavity Squamous Cell Carcinoma
Locally Advanced Oropharyngeal Squamous Cell Carcinoma
Malignant Posterior Tongue Neoplasm
Stage II Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
Stage II Hypopharyngeal Carcinoma AJCC v8
Stage II Laryngeal Cancer AJCC v8
Stage II Nasopharyngeal Carcinoma AJCC v8
Stage II Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
Stage III Hypopharyngeal Carcinoma AJCC v8
Stage III Laryngeal Cancer AJCC v8
Stage III Nasopharyngeal Carcinoma AJCC v8
Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Unresectable Head and Neck Squamous Cell Carcinoma
Unresectable Oropharyngeal Squamous Cell Carcinoma
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2021-05-04
Enrollment: 3
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 phase I trial studies the side effects of image-guided hyper-fractioned proton therapy in treating patients with head and neck cancer that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable). Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. The change in dose radiation frequency and dose investigated in this study may help to better control the tumor and prevent it from coming back or growing. The goal of this study is to test a new radiation schedule that administers more radiation to the tumor tissue using image guided proton therapy for patients that have a high risk of having a tumor recurrence (the tumor comes back after treatment).

Detailed description: PRIMARY OBJECTIVE:

I. To assess the safety \& feasibility of image guided mid-treatment hyper-fractioned dose-escalation with proton therapy and identify the maximum tolerable dose (MTD) for the treatment of locally advanced human papillomavirus (HPV) negative head and neck cancer.

OUTLINE:

Patients undergo radiation therapy once daily (QD) 5 days a week (Monday through Friday) for the first 18 days and then twice daily (BID) for 15 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 8 weeks, 3, 6, 9, and 12 months in the first year after radiation therapy, every 4 months in the second year after radiation therapy, and then every 9 months thereafter.

Eligibility criteria: Inclusion Criteria:

* Biopsy proven diagnosis of squamous cell carcinoma of head and neck cancer originating in the oropharynx, hypopharynx, larynx, oral cavity (base of tongue) or nasopharynx. Clinical evidence should be documented, and may consist of imaging, endoscopic evaluation, palpation, and should be sufficient to estimate the image tumor characteristic of the primary tumor
* Negative for HPV by p16 immunohistochemistry (IHC) or in situ hybridization (ISH)
* Inoperable locally advances disease, i.e. stage \>= III and T stage \>= 2
* The primary radiotherapy, either in combination with chemotherapy or not, with curative intent
* No head and neck surgery of the primary tumor or lymph nodes except for incisional or excisional biopsies
* Eastern Cooperative Oncology Group (ECOG) = 0, 1, or 2
* For females of child-bearing age, a negative pregnancy test

Exclusion Criteria:

* Patients who have undergone definitive resection of their primary or nodal disease as well as any chemotherapy or radiation therapy for their head and neck squamous cell carcinoma (HNSCC)
* Patient that refuse or are unable to stop smoking and/or consuming alcohol during and after radiotherapy. In addition, patients that refuse or fail tobacco and alcohol blood test
* Patients that have no detectable no tumor in both the primary site and lymph nodes at week 4 in treatment, because there will not be a volume to boost
* Patients unable or unwilling to give written, informed consent or to undergo magnetic resonance imaging (MRI) imaging
* Women of childbearing potential (a woman of child-bearing potential is a sexually mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months \[i.e., who has had menses at any time in the preceding 24 consecutive months\]). Male partners 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 to tolerate intravenous contrast for both computed tomography (CT) and MRI, having an estimated glomerular filtration rate (GFR) \< 60 ml/min/1.73 m\^2 or any contraindications to gadolinium-based contrast agents
* Contraindications to iron supplementation include hemochromatosis, colitis, history of gastrointestinal (GI) bleeds, alcoholism, or liver disease. Ferumoxytol is contraindicated in patients with evidence of iron overload and/or known hypersensitivity to Feraheme or any of its components. Consequently, we will plan to exclude patients who have symptoms or signs that might be caused by iron overload. These include patients with (unexplained): arthritis (including premature osteoarthritis), congestive heart failure or cardiomyopathy, adult-onset diabetes, secondary hypogonadism, increased skin pigmentation, or patients with persistently elevated serum ferritin not explained by an underlying inflammatory/systemic disease, unless these patients demonstrate a fasting transferrin saturation =\< 0.45
* Patients with any evidence of iron overload on pre-imaging laboratory studies

Primary outcomes:
measure: Incidence of severe unacceptable local adverse events which are radio therapeutically attributable
timeFrame: Up to 6 months after radiation therapy
Secondary outcomes:
measure: Incidence of grade 3 toxicity
timeFrame: At 3-6 months after radiation therapy
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Clifton D Fuller
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Dijk LV, Frank SJ, Yuan Y, Gunn B, Moreno AC, Mohamed ASR, Preston KE, Qing Y, Spiotto MT, Morrison WH, Lee A, Phan J, Garden AS, Rosenthal DI, Langendijk JA, Fuller CD. Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients [PIRATES]: A Phase I safety and feasibility trial of MRI-guided adaptive particle radiotherapy. Clin Transl Radiat Oncol. 2021 Nov 11;32:35-40. doi: 10.1016/j.ctro.2021.11.003. eCollection 2022 Jan.