Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

Preoperative Hypofractionated Radiation Followed by Surgery in Advanced Oral Cavity Squamous Cell Carcinoma

This phase I/II trial studies how well hypofractionated radiation therapy followed by surgery works in treating patients with squamous cell carcinoma of the oral cavity that has spread to other places in the body. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving hypofractionated radiation therapy before surgery may shrink the tumor making it easier to be removed, may reduce the risk of the cancer coming back, and may be a better treatment for squamous cell carcinoma of the oral cavity.

Study Overview

• Status: Withdrawn
• Conditions: Tongue Cancer; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
• Intervention / Treatment: Other: laboratory biomarker analysis; Procedure: therapeutic conventional surgery; Radiation: hypofractionated radiation therapy; Radiation: intensity-modulated radiation therapy

Detailed Description

PRIMARY OBJECTIVES:

I. 2 year locoregional control for advanced oral cavity squamous cell carcinoma (SCC) treated with preoperative hypofractionated radiation followed by surgical resection.

SECONDARY OBJECTIVES:

I. Rate of pathologic complete response after preoperative hypofractionated radiation at both the primary site and lymph nodes (LN).

II. Rate of radiologic complete and partial response (computed tomography [CT] neck with intravenous [IV] contrast performed before and after radiation therapy, judged per Response Evaluation Criteria In Solid Tumors [RECIST] 1.1 criteria).

III. Grade III/IV/V toxicity both short term (from start of radiation to 60 days after surgery) and long term (more than 60 days after surgery).

IV. Rate of flap complications: Rate of flap revisions, and complete revisions required.

V. Molecular correlates. VI. Quantitative imaging correlates.

OUTLINE:

Patients undergo hypofractionated intensity-modulated radiation therapy (IMRT) every other day for up to 5 treatments. Patients then undergo surgery 7-14 days after the last radiation treatment.

After completion of study treatment, patients are followed up every 3 months for 2 years.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • Newark, New Jersey, United States, 07103
      • New Jersey Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient is willing to sign study specific informed consent
• Pathologically proven (histologically or cytologically) diagnosis of squamous cell carcinoma (including histological variants like papillary squamous cell carcinoma and basaloid squamous cell carcinoma)
• Advanced stage but not metastatic SCC of the oral cavity (III or IVa, b); sites in the oral cavity include oral tongue, floor of mouth, hard palate, gingiva, buccal mucosa, retromolar trigone; often, head & neck tumors may involve other adjacent sites, such as the oropharynx- in these cases, the criteria is that the tumor must appear to have originated in the oral cavity per ear, nose, and throat (ENT)/radiation oncology
• Patient is deemed to be a surgical candidate by ENT
• Karnofsky performance status (KPS) 0-2
• For women of childbearing potential, a negative serum pregnancy test completed prior to any radiation therapy
• Patients with human immunodeficiency virus (HIV) infection are not automatically excluded, but must meet the following criteria: cluster of differentiation 4 (CD4) count is > 499/cu mm and their viral load is < 50 copies/ml; use of highly active antiretroviral therapy (HAART) is allowed
• Patient is free of any prior invasive malignancy (except non-melanomatous skin cancer) for a minimum of the past 3 years

Exclusion Criteria:

• Metastatic disease beyond the neck or supraclavicular area as demonstrated by positron emission tomography (PET)/CT or biopsy
• KPS 3 or worse
• Gross disease in the retrostyloid (high level II) or retropharyngeal lymph node regions by CT or PET/CT
• Patients may not have received previous therapy for their head and neck SCC, including chemotherapy, radiation therapy, or surgery beyond biopsy
• Second primary malignancy; exceptions are 1) patient had a second primary malignancy but has been treated and disease free for at least 3 years, 2) in situ carcinoma (e.g. in situ carcinoma of the cervix), 3) non-melanomatous carcinoma of the skin
• Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator; this includes scleroderma
• Women who are pregnant; women of childbearing age must agree to undergo a urine pregnancy test prior to therapy and to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 6 months after; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Patient is deemed to not be a surgical candidate by ENT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (hypofractionated IMRT, surgery); Patients undergo hypofractionated IMRT every other day for up to 5 treatments. Patients then undergo surgery 7-14 days after the last radiation treatment.	Other: laboratory biomarker analysis; Correlative studies; Procedure: therapeutic conventional surgery; Undergo surgery; Radiation: hypofractionated radiation therapy; Undergo hypofractionated IMRT; Radiation: intensity-modulated radiation therapy; Undergo hypofractionated IMRT; Other Names: IMRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Locoregional control	Will be assessed using both clinical and radiographic means, and recurrence will be confirmed by biopsy.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of pathologic complete response after preoperative hypofractionated radiation at both the primary site and lymph nodes		Up to 2 years
Rate of complete and partial response per imaging, judged per RECIST 1.1 criteria	CT neck with IV contrast will be performed before and after radiation therapy.	Up to 2 years
Incidence of short term grade III/IV/V toxicity, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0	Interim analysis will be used for grade IV toxicity (death).	Up to 60 days post-surgery
Incidence of long term grade III/IV/V toxicity, graded according to the NCI CTCAE, version 4.0		Up to 2 years
Rate of flap complications (rate of flap revisions and flap complete revisions required)		Up to 2 years
Expression of molecular markers	Will correlate molecular markers (especially those relating to radioresitance such as B-cell lymphoma 2 or autophagy markers to locoregional control).	Up to 24 hours after initial radiation treatment
Quantitative imaging characteristics in the pre-treatment PET/CT	Includes max/peak/total/mean standard uptake value, the metabolic tumor volume, and the total lesion glycolysis. These imaging findings will be correlated to clinical outcomes such as pathological response and locoregional control.	Baseline
Changes from CT to CT (after radiation), such as changes in tumor volume or longest tumor diameter	These imaging findings will be correlated to clinical outcomes such as pathological response and locoregional control.	Baseline to up to 2 years

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI); Rutgers Cancer Institute of New Jersey
• Investigators: Principal Investigator: Sung Kim, Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: November 17, 2014
• First Submitted That Met QC Criteria: November 17, 2014
• First Posted (Estimate): November 20, 2014

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 27, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Neoplasms, Squamous Cell; Mouth Neoplasms; Tongue Diseases; Carcinoma; Carcinoma, Squamous Cell; Carcinoma, Verrucous; Tongue Neoplasms
• Other Study ID Numbers: Pro20140000684; P30CA072720 (U.S. NIH Grant/Contract); NCI-2014-02215 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 031401 (Other Identifier: Rutgers Cancer Institute of New Jersey)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No