Involved Nodal Radiotherapy versus Elective Neck Radiotherapy for the Treatment of Stage I-IVB Oropharyngeal, Laryngeal, and Hypopharyngeal Squamous Cell Cancer, The INVERT Trial

Status: active

This phase II trial studies compares involved nodal radiotherapy versus elective neck radiotherapy in treating patients with stage I-IVB oropharyngeal, laryngeal, and hypopharyngeal squamous cell cancer. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. The historical, standard method for treating microscopic cancerous tissue in the neck is to deliver radiation to the entire area, including normal-appearing tissues, in a treatment called elective nodal radiation (ENI). A new method, called involved nodal radiotherapy (INRT), the radiation is focused just on the lymph nodes that may hold this microscopic disease. Radiotherapy and chemotherapy are commonly used together for patients with head and neck cancer. Chemotherapy drugs used in this trial, such as cisplatin, cetuximab, carboplatin, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. INRT may be as effective and easy to handle, or even better, than ENI in treating stage I-IVB oropharyngeal, laryngeal, and hypopharyngeal squamous cell cancer, both in the short- and long-term with or without chemotherapy.

Inclusion Criteria

Pathologically-proven diagnosis of squamous cell carcinoma of the oropharynx, larynx, or hypopharynx. Squamous cell carcinoma of unknown primary is not allowed.
Patients must have clinically or radiographically evident measurable disease at the primary site and/or nodal stations. Diagnostic lymph node excision (≤ 2 nodes) is also allowable.
Patients may undergo a diagnostic or therapeutic transoral resection for a T1-2 tonsil or base of tongue cancer.
Clinical stage I-IVB (American Joint Committee on Cancer [AJCC], 7th edition); stages I-II glottic cancer are excluded.
Age ≥ 18 years.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: ** Has not undergone a hysterectomy or bilateral oophorectomy; or ** Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Neck CT and/or neck MRI, and PET-CT
Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria

Distant metastasis.
Inability to undergo either a diagnostic CT with contrast or simulation CT with contrast.
Inability to undergo PET-CT.
Stage I and II glottic carcinoma.
Gross total excision of both the primary and nodal disease.
Synchronous non-skin cancer primaries outside of the oropharynx, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous well-differentiated thyroid cancer; in the latter case, surgery may occur before or after treatment, provided all other eligibility criteria are met.
Prior invasive malignancy with an expected disease-free interval of less than 3 years.
Prior systemic chemotherapy for the study cancer; prior chemotherapy for a remote cancer is allowable.
Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields.
Subjects may not be receiving any other investigational agents.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy agents in this study (if necessary).
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, in the opinion of the investigator, would limit compliance with study requirements.
History of severe immunosuppression, including HIV, and organ or autologous or allogeneic stem cell transplant.

PRIMARY OBJECTIVE:

I. To determine the risk of solitary elective volume recurrence following INRT versus ENI.

SECONDARY OBJECTIVES:

I. To compare the incidence of acute grade 2+ acute dermatitis in patients treated with INRT versus ENI.

II. To compare the incidence of grade 3+ dysphagia in patients treated with INRT versus ENI.

III. To compare the MD Anderson Dysphagia Inventory (MDADI) composite score at 2 years following treatment in patients treated with INRT versus ENI.

EXPLORATORY OBJECTIVES:

I. To determine the rate of grade 3-5 acute (start of treatment through 90 days from the completion of treatment) and late (after 90 days from the completion of treatment) adverse events, according to National Cancer Institute's (NCI’s) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 toxicity criteria in patients treated with INRT versus ENI.

II. To compare the overall survival probability at 2 years from the start of treatment in patients treated with INRT versus ENI.

III. To compare the progression-free survival probability at 2 years from the start of treatment in patients treated with INRT versus ENI.

IV. To compare the cumulative incidence of locoregional recurrence at 2 years, with death as a competing risk in patients treated with INRT versus ENI.

V. To compare the University of Washington Quality-of-Life (UWQOL) Scores score at 2 years following treatment in patients treated with INRT versus ENI.

VI. To compare the Xerostomia Questionnaire (XQ) score at 2 years following treatment in patients treated with INRT versus ENI.

VII. To compare the diffusion weighted imaging (DWI) and dynamic contrast-enhanced (DCE) characteristics at baseline and at 3 weeks in patients with and without locoregional recurrence and/or distant metastasis (for those patients on the optional magnetic resonance imaging [MRI] study).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A:

* STAGE I DISEASE: Patients receive standard-of-care (SOC) elective nodal irradiation (ENI) once daily (QD), Monday through Friday, over 35 treatment sessions in the absence of disease progression or unacceptable toxicity.

* STAGE II DISEASE: Patients receive either: 1) SOC ENI QD, Monday through Friday, over 35 treatment sessions OR 2) accelerated ENI QD, 6 days per week, over 35 treatment sessions in absence of disease progression or unacceptable toxicity.

* STAGE III DISEASE: Patients receive either: 1) SOC ENI QD, Monday through Friday, over 35 treatment sessions AND chemotherapy consisting of one of the following per treating physician discretion: a) cisplatin intravenously (IV) every 3 weeks (Q3W), b) cisplatin IV over 5 hours weekly (QW), c) cetuximab IV over 3 hours QW, d) carboplatin IV over 3 hours and paclitaxel IV over 3 hours QW in absence of disease progression or unacceptable toxicity, OR 2) accelerated ENI QD, 6 days per week, over 35 treatment sessions in absence of disease progression or unacceptable toxicity.

STAGE IVA-IVB DISEASE: Patients receive SOC ENI QD, Monday through Friday, over 35 treatment sessions AND chemotherapy consisting of one of the following per treating physician discretion: a) cisplatin intravenously (IV) every 3 weeks (Q3W), b) cisplatin IV over 5 hours weekly (QW), c) cetuximab IV over 3 hours QW, d) carboplatin IV over 3 hours and paclitaxel IV over 3 hours QW in absence of disease progression or unacceptable toxicity.

ARM B: Patients receive INRT QD, Monday through Friday, over 35 treatment sessions in the absence of disease progression or unacceptable toxicity.

All patients also undergo computed tomography (CT) of the neck during screening, CT or magnetic resonance imaging (MRI) of the neck during follow-up, and positron emission tomography (PET)-CT throughout the trial. Patients may also undergo optional multi-parametric MRI on study.

After completion of study treatment, patients are followed up at 1 month, at 11-14 weeks, then at 6, 12, and 24 months.

Have a question?
We're here to help

Chat with us: LiveHelp
Call us: 1-800-4-CANCER
(1-800-422-6237)

Which trials are right for you?

Use the checklist in our guide to gather the information you’ll need.

Involved Nodal Radiotherapy versus Elective Neck Radiotherapy for the Treatment of Stage I-IVB Oropharyngeal, Laryngeal, and Hypopharyngeal Squamous Cell Cancer, The INVERT Trial

Inclusion Criteria

Exclusion Criteria

United States

Texas

Dallas

Have a question?
We're here to help

Which trials are right for you?

Involved Nodal Radiotherapy versus Elective Neck Radiotherapy for the Treatment of Stage I-IVB Oropharyngeal, Laryngeal, and Hypopharyngeal Squamous Cell Cancer, The INVERT Trial

Description

Eligibility Criteria

Locations & Contacts

Trial Objectives and Outline

Trial Phase & Type

Lead Organization

Trial IDs

Have a question?We're here to help

Which trials are right for you?

Have a question?
We're here to help