Trial of De-Intensified Post-operative Chemoradiation Following Robotic Surgery for HPV-positive Oropharyngeal Cancer

NCT ID: NCT04502407

Last Updated: 2025-09-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-16
• Study Completion Date: 2029-12-15

Brief Summary

This study will enroll patients with HPV-associated oropharyngeal cancer, undergoing resection of all gross visible disease at the primary site and in the lymph nodes. A total of 40 patients who have had or will require surgery to remove cancer cells prior to starting chemoradiation may be enrolled. All eligible patients will receive de-intensified cisplatin-based chemoradiation, with high-risk patients receiving a higher dose and longer treatment period than other patients on the study. The study will assess whether a de-intensified version of standard chemoradiation treatment will be just as effective in treating HPV-associated oropharyngeal cancer while causing less side effects than standard dosing.

Detailed Description

This is a single arm phase II study that will enroll patients with HPV-associated oropharyngeal cancer, undergoing resection through trans-oral robotic surgery (TORS) of all gross visible disease at the primary site and in the lymph nodes. A total of 36 patients at Cedars-Sinai Medical Center and its affiliates (Tower Hematology-Oncology, Torrance Memorial Physician Network) who have had or will require surgery to remove cancer cells prior to starting chemoradiation may be enrolled. All eligible patients will receive de-intensified cisplatin-based chemoradiation, with high-risk patients receiving a higher dose and longer treatment period than other patients on the study. The treatment period will last 3 to 5 weeks depending on whether the patient is considered high-risk or not. The study will assess whether a de-intensified version of standard chemoradiation treatment will be just as effective in treating HPV-associated oropharyngeal cancer while causing less side effects than standard dosing.

Conditions

HPV Positive Oropharyngeal Squamous Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

De-intensified Cisplatin-based Chemoradiation

This is a non-randomized study, with all patients undergoing de-intensified post-operative cisplatin-based chemoradiation. Dosage level and duration of administration will be determined by whether the patient is high risk or not as assessed by the treating investigator.

Group Type: EXPERIMENTAL

Cisplatin-based Radiation Therapy

Intervention Type: RADIATION

• High risk patients who are patients with positive margins, extranodal extension, or ≥5 positive lymph nodes will receive radiation dose of 50 Gy in 25 fractions over 5 cycles on Days 1, 8, 15, 22, and 29 of radiation treatment.
• All other patients will receive radiation dose of 30 Gy in 15 fractions over 3 cycles on Days 1, 8 and 15 of radiation treatment.

Cisplatin Chemotherapy

Intervention Type: DRUG

• High risk patients who are patients with positive margins, extranodal extension, or ≥5 positive lymph nodes will receive 5 cycles of weekly chemotherapy of cisplatin 40mg/m2 given intravenously (IV) on Days 1, 8, 15, 22, and 29 of radiation.
• All other patients will receive 3 cycles of weekly chemotherapy of cisplatin 40mg/m2 given intravenously (IV) on Days 1, 8 and 15 of radiation.

Interventions

Cisplatin-based Radiation Therapy

• High risk patients who are patients with positive margins, extranodal extension, or ≥5 positive lymph nodes will receive radiation dose of 50 Gy in 25 fractions over 5 cycles on Days 1, 8, 15, 22, and 29 of radiation treatment.
• All other patients will receive radiation dose of 30 Gy in 15 fractions over 3 cycles on Days 1, 8 and 15 of radiation treatment.

Intervention Type: RADIATION

Cisplatin Chemotherapy

• High risk patients who are patients with positive margins, extranodal extension, or ≥5 positive lymph nodes will receive 5 cycles of weekly chemotherapy of cisplatin 40mg/m2 given intravenously (IV) on Days 1, 8, 15, 22, and 29 of radiation.
• All other patients will receive 3 cycles of weekly chemotherapy of cisplatin 40mg/m2 given intravenously (IV) on Days 1, 8 and 15 of radiation.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Zachary Zumsteg

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zachary S Zumsteg, MD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

Tower Hematology-Oncology

Beverly Hills, California, United States

Cedars-Sinai Medical Center (Beverly - Main Site)

Los Angeles, California, United States

Valley Oncology Medical Group

Tarzana, California, United States

Torrance Memorial Physician Network Cancer Care

Torrance, California, United States

Countries

United States

Other Identifiers

IIT2019-20-Zumsteg-HPVOPC

Identifier Type: -

Identifier Source: org_study_id