This is a Phase I study looking to evaluate the safety of dose escalated stereotactic radiotherapy (SRS) without exceeding the maximum tolerated dose in patients with high-risk human papilloma virus (HPV)- unassociated oropharyngeal squamous cancer.
Active, not recruiting
N/A
Human Papilloma Virus (HPV) is frequently found within tumor cells removed from patients
diagnosed with oropharynx cancer. Tumors which do not contain HPV virus (termed
"HPV-Negative") are not cured as frequently by radiation therapy. Tumors which do contain HPV
in patients who have a history of cigarette smoking also are not cured as frequently by
radiation.
One way to potentially overcome this challenge is to deliver a more intense dose of radiation
treatment to the tumor. The standard way to deliver radiation, termed Intensity Modulated
Radiotherapy (IMRT), can protect normal tissues near tumors to a certain degree but not
completely. Stereotactic radiosurgery (SRS) is a technique which can deliver radiation more
precisely.
This trial will test the safety of treating HPV-unassociated oropharynx tumors to higher
radiation doses wth SRS (termed a "boost") after a standard course of IMRT has been given. In
addition, the investigators will look at whether magnetic resonance imaging (MRI) scanning
can detect treatment response in oropharynx tumors earlier than with standard tests.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Cohort 1 | Experimental | Patients will receive 6 weeks of Intensity-Modulated Radiation Therapy (IMRT) (standard of care) followed by the dose escalated stereotactic radiosurgery (SRS Boost). Cohort 1 will receive 8 Gy in a single fraction, cohort 2 will receive 10 Gy in a single fraction and cohort 3 will receive 10 Gy split into two fractions. |
Inclusion Criteria:
- Patients older than 18 years of age with histologically proven squamous cell carcinoma
of the oropharynx
- HPV-negative disease status by routine p16 immunohistochemical (IHC) staining or in
situ hybridization (ISH) of biopsied tumor tissue or >10 pack-year cigarette smoking
history
- Stage T1-4, N0-3 disease, as defined by American Joint Committee on Cancer (AJCC)
criteria
- Eastern Cooperative Oncology Group (ECOG) (Zubrod) Performance Status 0-2.
Exclusion Criteria:
- Patients who have undergone resection of primary disease
- Patients who have received induction chemotherapy for their oropharynx cancer
diagnosis
- Prior cancer diagnosis within 5 years, 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 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 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
- Patient unable to tolerate MRI or having an estimated Glomerular Filtration Rate (GFR)
<60 ml/min/1.73 m2.
- Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the
last 6 months
- Transmural myocardial infarction within the last 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of
registration
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days before
registration
- 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
- Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease
Control (CDC) definition; note, however, that HIV testing is not required for entry
into this protocol. The need to exclude patients with AIDS from this protocol is
necessary because the treatments involved in this protocol may be significantly
immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised
patients
- History or treatment with potent immunosuppressive drugs for such conditions as organ
transplant, severe rheumatoid arthritis, etc. within the past 6 months.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Safety and dose-limiting toxicity of dose escalated stereotactic radiotherapy in patients with high-risk oropharyngeal squamous cancer using (CTCAE), version 4.03 |
| Time Frame: | up to five years post SRS Boost |
| Safety Issue: | |
| Description: |
| Measure: | Disease response using Revised RECIST guideline (version 1.1) |
| Time Frame: | up to five years post SRS Boost |
| Safety Issue: | |
| Description: |
| Phase: | N/A |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Northwell Health |
May 21, 2019
