Using CircuLating Tumor DNA to Risk Adapt Post-Operative Therapy for HPV-associated Oropharyngeal Cancer

NCT06445114 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IIT2023-14-ZUMSTEG-ULTRA-HPV
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 4

Brief Summary

This is a single institution phase II study that will enroll patients with T0-3N0-2 p16-positive oropharyngeal squamous cell carcinoma (OSCC) undergoing resection of all gross visible disease at the primary site and in the lymph nodes.

Conditions

Oropharyngeal Cancer; Carcinoma

Keywords

Transoral Robotic Surgery (TORS); pT0 tumors (unknown primary); p16

Outcome Measures

Primary Outcomes (1)

• 2-year progression-free (PFS)

  The primary objective of this study is to assess the 2-year progression-free survival (PFS) of de-intensified post-operative chemoradiation in patients with HPV-associated oropharyngeal cancer when basing treatment intensity on both standard pathologic features and post-operative Blood-based circulating tumor tissue modified viral (cTTMV-HPV DNA)

  2 Years

Secondary Outcomes (13)

• Overall Survival (OS)

  2 Years

• Locoregional Control

  2 Years

• Distant Control

  2 Years

• Cause-Specific Survival

  2 Years

• Mean change in patient-reported outcomes using Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

  2 Years

Study Arms (1)

Single Arm

EXPERIMENTAL

Low risk pathology with post-op HPV DNA (-): cisplatin-based chemoradiation with 30 Gy in 15 fractions and 3 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, and 15 of radiation. Low risk pathology with post-op HPV DNA (+): cisplatin-based chemoradiation with 40 Gy in 20 fractions and 4 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, and 22 of radiation. High risk pathology with post-op HPV DNA (-), excluding patients with both 5 LN+ and ENE+ or pre-op HPV DNA≤12 copies/mL: cisplatin-based radiation with 40 Gy in 20 fractions and 4 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, and 22 of radiation. High risk pathology with post-op HPV DNA (+) OR pre-op HPV DNA≤12 copies/mL OR both 5 or more LN+ and ENE+: cisplatin-based radiation with 50 Gy in 25 fractions with 5 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, 22, and 29 of radiation.

Drug: Cisplatin

Interventions

Cisplatin DRUG

Low risk pathology with post-op HPV DNA (-): cisplatin-based chemoradiation with 30 Gy in 15 fractions and 3 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, and 15 of radiation. Low risk pathology with post-op HPV DNA (+): cisplatin-based chemoradiation with 40 Gy in 20 fractions and 4 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, and 22 of radiation. High risk pathology with post-op HPV DNA (-), excluding patients with both 5 LN+ and ENE+ or pre-op HPV DNA≤12 copies/mL: cisplatin-based radiation with 40 Gy in 20 fractions and 4 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, and 22 of radiation. High risk pathology with post-op HPV DNA (+) OR pre-op HPV DNA≤12 copies/mL OR both 5 or more LN+ and ENE+: cisplatin-based radiation with 50 Gy in 25 fractions with 5 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, 22, and 29 of radiation.

Also known as: Chemoradiation

Single Arm

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 is strongly positive by immunohistochemistry or high-risk HPV is detected by in-situ hybridization.
• Have undergone or will undergo gross total resection of all known disease in the head and neck via transoral robotic surgery. For patients with clinical unknown primary tumors, a patient must undergo both ipsilateral tonsillectomy and base of tongue resection unless the primary is identified clinically or pathologically at the time of surgery. If the primary is identified, then only resection of the primary site is required. If the primary tumor is resected with negative margins with a non-robotic surgery, such as a diagnostic tonsillectomy, this is considered acceptable and further robotic surgery is not necessary.
• 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
• Contralateral lymph node involvement
• 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.
• Patients consented preoperatively are required to have detectable cTTMV-HPV DNA based on pre-operative NavDx testing. For patients consented post-operatively, NavDx testing should be performed on the tumor tissue to ensure detectable HPV DNA and for HPV subtyping.

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.
• 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 enrollment
• Hepatic insufficiency resulting in clinical jaundice and/or known coagulation defects
• Moderate to severe hearing loss.
• Active connective tissue disease (e.g. systemic lupus erythematous, scleroderma) requiring immunosuppression.
• Pregnant or breast-feeding women.
• Prior allergic reaction to cisplatin.

Sponsors & Collaborators

• Zachary Zumsteg: lead

Study Sites (4)

Cedars-Sinai Cancer at Beverly Hills (THO)

Beverly Hills, California, 90211, United States

RECRUITING

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

CS Cancer at Valley Oncology Medical Group

Tarzana, California, 91356, United States

RECRUITING

CS Cancer at the Hunt Cancer Center

Torrance, California, 90505, United States

RECRUITING

MeSH Terms

Conditions

Oropharyngeal Neoplasms; Carcinoma

Interventions

Cisplatin; Chemoradiotherapy

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• Zachary S Zumsteg, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trial Navigator

CONTACT

3104232133; cancer.trial.info@cshs.org

Study Design

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

Model Details: Prospective single arm multicenter clinical trial

Study Record Dates

• First Submitted: May 22, 2024
• First Posted: June 6, 2024
• Study Start: May 12, 2025
• Primary Completion (Estimated): June 1, 2032
• Study Completion (Estimated): June 1, 2032
• Last Updated: November 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)