A Study on Using Cell-Free Tumor DNA (ctDNA) Testing to Decide When to StartRoutine Treatment in People With Human Papilloma Virus (HPV)- Associated Oropharynx Cancer (OPC)

Официальное название

Phase II Trial Evaluating Selective Minimal Residual Disease Directed Adjuvant Radiation in Human Papilloma Virus Associated Oropharynx Carcinoma

Обзор

This study will look at whether monitoring HPV ctDNA levels is an effective way to detect cancer relapse risk in people with HPV-OPC. All participants will have recently had surgery to treat their disease, or they will be scheduled to have this surgery. In Arm A the researchers will see whether monitoring participants' HPV ctDNA levels can safely identify patients who do not need radiation therapy (RT) after surgery and whose RT can be delayed until their HPV ctDNA levels become detectable. In Arm B, the researchers will see whether patients who usually need 6-6.5 weeks of CRT can be selected by HPV ctDNA to receive 3 weeks of CRT.

Вмешательства

• Диагностический тест HPV ctDNA Assay
  HPV ctDNA evaluation will be completed using NavDx which is a validated digital droplet PCR (ddPCR) assay that targets primers and hydrolysis probes to specifically detect amplicons within the E6 and E7 genes encoded by high-risk HPV strain 16, and the E7 gene for high-risk HPV strains: 18, 31, 33, and 35.
• Диагностический тест MRI Studies
  Research MRI studies will be acquired at Memorial Sloan Kettering using a fast multi-phase spoiled gradient echo sequence. A Gadolinium-based agent will be used for DCE-MRI studies.
• Поведенческое EORTC QLQ H&N 35 and C30
  The EORTC QLQ H\&N 35 s a validated 35-item site specific assessment tool. The module uses 7 multi-item scales to measure problems with swallowing, senses, speech, social eating and social contact. In addition, 11 single-item scales are utilized in assessing problems with teeth, mouth opening, dry mouth, sticky saliva, coughing, feeling ill, as well as use of analgesics, nutritional supplements, feeding tube and finally, weight gain and weight loss. All of the scales and single item measures ran
• Поведенческое MDADI-HN
  The MDADI-HN is a questionnaire scored on a scale of 1 to 5, consisting of global, emotional, functional, and physical subscales. The MDADI-HN evaluates the effects of dysphagia on QOL.
• Поведенческое COST-FACIT
  Comprehensive Score for financial Toxicity or COST survey is a validated screening tool to assess objective and subjective questions about treatment-related financial distress. It is scored from 0-44, where lower composite scores reflect greater risk of financial toxicity.
• Лучевая терапия Intensity-Modulated Radiation Therapy (Arm A)
  59.4-60 Gy in 1.8-2 Gy fractions: CTV\_primary, Involved/Adjacent to nodal levels. 50 Gy to this volume is allowed as per MSK institutional standards in patients with clear or close margins and 2-4 involved nodes. 45-50.4 Gy in 1.8-2 Gy fractions: Dissected node positive neck: uninvolved levels that are not adjacent to positive node - Dissected node negative neck
• Комбинированный продукт Chemoradiation (Arm B)
  30 Gy in 2 Gy fractions: CTV\_primary, CTV\_node-positive neck, CTV\_node-negative neck, received de-escalated postoperative chemoradiation. Adjuvant radiation will be administered as previously outlined. Concurrent chemotherapy will be administered as per standard of care. Cisplatin will be administered concurrently with radiation. For non-cisplatin candidates, carboplatin/5fu will be administered. Reasons for using carboplatin/5FU instead of cisplatin need to be charted in the medical record,

Первичные конечные точки

• Pathologically confirmed progression free survival [Срок оценки: 2 years]

Критерии участия

Критерии включения

• Age ≥ 18
• ECOG 0-2
• HPV-16 squamous cell carcinoma of the oropharynx or HPV-16 head and neck squamous cell carcinoma of unknown primary . HPV status must be confirmed by in-situ hybridization.
• HPV ctDNA detectable by HPV digital PCR (Naveris assay) with a minimum of 50 copies/mL pre-operatively.
• Surgical resection of all gross disease with no gross disease visualized on post-operative imaging.

o For patients with pT0 (unknown primary) evaluation for the primary should include PET/CT, direct laryngoscopy, ipsilateral tonsillectomy, and targeted biopsy. This should be followed by a neck dissection.

• Two, undetectable (<1 copy/mL) post-operative HPV ctDNA within 2-6 weeks following surgery (blood drawn at least one week apart preferred).
• A minimum of one of the following pathologic criteria: (Arm A)

• AJCC 7 Stage: pT0N1-N2b, pT1N1, pT2N1, or ≥pT3
• AJCC 7 ≥pN2
• Lymphovascular invasion
• Perineural invasion
• Close pathologic margin (≤ 3 mm)
• Signed informed consent form by the participant or their legally authorized representative (LAR).
• A minimum of one of the following pathologic criteria (Arm B):

• Microscopic positive margin
• Extracapsular extension
• Signed informed consent form by the participant or their legally authorized representative (LAR).

Additional criteria for Arm B only:

• Adequate hematologic function within 30 days prior to registration, defined as follows:

• White Blood Count (WBC) ≥ 2 K/mcL
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
• Platelets ≥ 100,000 cells/mm3
• Hemoglobin ≥ 8.0 g/dl; Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable
• Adequate renal function within 30 days prior to registration, defined as follows:

• Serum creatinine < 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula:
• CCr male = \[(140 - age) x (wt in kg)\] divided by \[(Serum Cr mg/dl) x (72)\]
• CCr female = 0.85 x (CrCl male)
• Adequate hepatic function within 30 days prior to registration, defined as follows:

\- Bilirubin < 2 mg/dl o AST or ALT < 3 x the upper limit of normal

• Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential

Критерии исключения

• Metastatic disease
• Non-HPV16 genotype (i.e. HPV-18,-31, -33, -35)
• Patients who receive surgery at outside institution. Exceptions can be made for high-volume surgical centers at the discretion of the PI/co-PI
• Prior head and neck radiation
• Patients without pre-operative HPV ctDNA or pre-operative HPV ctDNA ≤ 50 copies/mL
• Subjects with simultaneous primary cancers outside of the oropharynx

o Note: Exceptions can be made for patients with simultaneous primaries outside of the oropharynx if determined by the PI/Co-PI, then the patient can proceed with protocol activities

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 3 years or if cure rate from treatment at 5 years is 90% or greater

o Note: Exceptions can be made for patients with prior invasive malignancy if determined by the PI/Co-PI, then the patient can proceed with protocol activities

• Prior systemic chemotherapy for the study cancer

o Note: prior chemotherapy for a different cancer is allowable

• 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 within 30 days of registration
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• Lack of ability to understand and willingness to sign a written informed consent and complete questionnaires.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

США · 8 центров

• Baptist Alliance MCI (Data Collection Only) — Miami
• Memorial Sloan Kettering Basking Ridge (Limited protocol activities) — Basking Ridge
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale
• Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities) — Commack
• Memorial Sloan Kettering Westchester (Limited Protocol Activites) — East White Plains
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York
• Memorial Sloan Kettering Nassau (Limited protocol activities) — Rockville Centre

Идентификаторы

NCT: NCT05307939 · 21-434

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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