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

NCT04502407 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IIT2019-20-Zumsteg-HPVOPC
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

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.

Conditions

HPV Positive Oropharyngeal Squamous Cell Carcinoma

Keywords

cisplatin; chemoradiation

Outcome Measures

Primary Outcomes (1)

• 2-Year Progression-Free Survival (PFS)

  Proportion of patients alive and without evidence of local, regional, or distant recurrence at 2 years from study enrollment.

  2 years

Secondary Outcomes (13)

• Overall Survival (OS)

  2 years

• Local Control

  2 years

• Regional Control

  2 years

• Locoregional Control

  2 years

• Distant Control

  2 years

Study Arms (1)

De-intensified Cisplatin-based Chemoradiation

EXPERIMENTAL

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.

Radiation: Cisplatin-based Radiation Therapy; Drug: Cisplatin Chemotherapy

Interventions

Cisplatin-based Radiation Therapy 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.

De-intensified Cisplatin-based Chemoradiation

Cisplatin Chemotherapy 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.

De-intensified Cisplatin-based Chemoradiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• For patients with pT0 tumors (unknown primary), there must be at least one metastatic lymph node present in cervical level II.
• p16 should be strongly and diffusely positive in the nuclear and cytoplasmic component in greater than 70% of the tumor cells.
• 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.
• Have undergone or will undergo neck dissection.
• Have at least one of the following after surgery:
• Pathologic stage T3
• 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.
• Age ≥ 18 years old
• ECOG performance status 0 or 1 within 56 days of start of chemoradiation.

You may not qualify if:

• AJCC 8th edition pT4 or cN3 disease.
• Radiologic or clinical evidence of distant metastasis.
• Recurrent disease.
• Inability to achieve gross total resection at time of surgery.
• Greater than 56 days (8 weeks) after surgical resection of the primary site.
• Prior radiation to the head and neck \> 30 Gy.
• 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
• 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.
• Moderate to severe hearing loss.
• Active connective tissue disease (e.g. systemic lupus erythematous, scleroderma) requiring immunosuppression.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (4)

Tower Hematology-Oncology

Beverly Hills, California, 90211, United States

Location

Cedars-Sinai Medical Center (Beverly - Main Site)

Los Angeles, California, 90048, United States

Location

Valley Oncology Medical Group

Tarzana, California, 91356, United States

Location

Torrance Memorial Physician Network Cancer Care

Torrance, California, 90505, United States

Location

Study Officials

• Zachary S Zumsteg, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 4, 2020
• First Posted: August 6, 2020
• Study Start: February 16, 2021
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): December 15, 2029
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

US (4)