Chemoradiation Following Robotic Surgery for Oropharyngeal Cancer

What is the Purpose of this Study?

This study focuses on individuals who have been diagnosed with HPV-associated oropharyngeal cancer and have had or will require surgery to remove their cancer prior to starting chemoradiation. The purpose of the study is to determine whether delivering a lower dose of radiation (lower than standard therapy) is as effective in treating cancer after surgery while causing less side effects than standard therapy.

The study is designed to evaluate the investigational use of de-intensified, cisplatin-based chemoradiation. Cisplatin-based chemoradiation is a standard-of-care therapy in this disease, but standard therapy uses higher doses than what is delivered in this trial.

Participants will receive cisplatin-based treatment once a week during radiation intravenously (through the veins) and will be evaluated carefully for any side effects. Patients will receive either 3 weeks or 5 weeks of treatment, based on findings at the time of surgery.

Eligibility

1. AJCC 8th edition T0-3N0-2 p16-positive oropharyngeal (tonsil, base of tongue, glossotonsillar sulcus, soft palate, oropharyngeal wall) squamous cell carcinoma or squamous cell carcinoma of unknown primary involving the cervical lymph nodes. Cytologic diagnosis from a cervical lymph node is sufficient for diagnosis in the presence of clinical evidence of a primary tumor in the oropharynx.
2. For patients with pT0 tumors (unknown primary), there must be at least one metastatic lymph node present in cervical level II.
3. p16 should be strongly and diffusely positive in the nuclear and cytoplasmic component in greater than 70% of the tumor cells.
4. Have undergone or will undergo gross total resection of all known disease in the head and neck via transoral robotic surgery. For patients with unknown primary tumors, a minimum of an ipsilateral tonsillectomy and base of tongue resection is required.

Inclusion Criteria:

1. AJCC 8th edition T0-3N0-2 p16-positive oropharyngeal (tonsil, base of tongue, glossotonsillar sulcus, soft palate, oropharyngeal wall) squamous cell carcinoma or squamous cell carcinoma of unknown primary involving the cervical lymph nodes. Cytologic diagnosis from a cervical lymph node is sufficient for diagnosis in the presence of clinical evidence of a primary tumor in the oropharynx.
2. For patients with pT0 tumors (unknown primary), there must be at least one metastatic lymph node present in cervical level II.
3. p16 should be strongly and diffusely positive in the nuclear and cytoplasmic component in greater than 70% of the tumor cells.
4. Have undergone or will undergo gross total resection of all known disease in the head and neck via transoral robotic surgery. For patients with unknown primary tumors, a minimum of an ipsilateral tonsillectomy and base of tongue resection is required.
5. Have undergone or will undergo neck dissection.
6. Have at least one of the following after surgery:
* Pathologic stage T3
* 2 or more positive lymph nodes
* At least one lymph node \>3cm
* Lymphovascular invasion
* Perineural invasion
* Extranodal extension
* Close/positive margins: Close margins are considered \<3mm from the peripheral margins and \<1mm from the deep margin on the en bloc specimen, unless the area of close margin is re-resected and without carcinoma.
7. Age ≥ 18 years old
8. ECOG performance status 0 or 1 within 56 days of start of chemoradiation.
9. Women of childbearing potential require a negative serum or urine pregnancy test within 28 days prior to start of chemoradiation.
10. Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
11. Adequate hematologic and renal function within 30 days of start of chemoradiation, defined as:
* Hemoglobin ≥ 9.0 g/dL
* Platelets ≥ 100, 000 cells/mm3
* ANC ≥ 1.5 X 109/L
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase/alanine aminotransferase ≤ 3.0 x upper limit of normal (ULN)
* Serum creatinine ≤1.5 x upper limit of normal (ULN) OR a calculated creatinine clearance ≥60 mL/min

Exclusion Criteria:

1. AJCC 8th edition pT4 or cN3 disease.
2. Radiologic or clinical evidence of distant metastasis.
3. Recurrent disease.
4. Inability to achieve gross total resection at time of surgery.
5. Greater than 56 days (8 weeks) after surgical resection of the primary site.
6. Prior radiation to the head and neck \> 30 Gy.
7. Prior active invasive (not in situ) malignancy within the prior 2 years, excluding cutaneous basal cell or squamous cell carcinoma, low or intermediate risk prostate cancer, papillary thyroid cancer, AJCC 8th edition stage I-II breast cancer, or low grade non-Hodgkin lymphoma
8. 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
* Hepatic insufficiency resulting in clinical jaundice and/or known coagulation defects
* Uncontrolled Acquired Immune Deficiency Syndrome (AIDS), defined as a CD4 count \< 200 at screening or an AIDS-defining opportunistic infection within the last 6 months.
9. Moderate to severe hearing loss.
10. Active connective tissue disease (e.g. systemic lupus erythematous, scleroderma) requiring immunosuppression.
11. Pregnant or breast-feeding women.
12. Prior allergic reaction to cisplatin.
13. Live vaccines within 30 days prior to the first dose of chemoradiation. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral vaccine). Season influenza vaccines for injection are generally killed virus vaccines and are allowed; however intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines and are not allowed.

Show less

Where can I participate?

Cedars-Sinai Cancer at Beverly Hills (THO)
Cedars-Sinai Cancer at Hunt Cancer Center - TMPNCC (CSMC Affiliate)
Cedars-Sinai Cancer at SOCC
Cedars-Sinai Cancer at The Angeles Clinic and Research Institute
Cedars-Sinai Cancer at Valley Oncology

More about this Clinical Trial

What is the full name of this clinical trial?

IIT2019-20-ZUMSTEG-HPVOPC: Phase II Trial of De-Intensified Post-operative Chemoradiation Following Robotic Surgery for HPV-positive Oropharyngeal Cancer

Study Details

Disease Type/Condition

Cancer of the mouth and throat associated with HPV

Principal Investigator

Zumsteg, Zachary

Co-Investigators

Alain Mita, Allen Ho, Andrew Horodner, Andrew Schumacher, Ani Balmanoukian, Benjamin King, Bryan Chang, Cathie T Chung, David Chan, David Hoffman, Evan Walgama, Hugo Hool, Inderjit Mehmi, Jeremy Lorber, Johnny Chang, Jon Mallen-St. Clair, Julie Huynh, Julie Jang, Jun Gong, Justin Wayne Tiulim, Kamalesh Sankhala, Kevin Scher, Kristopher Wentzel, Leland Green, Mark Faries, Michelle Offner, Natasha Banerjee, Omid Hamid, Robert Reznik, Ronald Natale, Ryan Ponec, Stephen Shiao, Swati Sikaria, Syed Jilani, Thomas Lowe, Thomas Simko, Thyra Endicott, Usama Mahmood, Vanessa Dickey, Vi K. Chiu

Age Group

Adult

Phase

IRB Number

STUDY00000900

ClinicalTrials.gov ID

NCT04502407

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org