Using blood tests to tailor radiation therapy for HPV-positive throat cancer
DART 2.0: ctHPV-DNA Informed De-Escalated Adjuvant and Definitive Radiation Therapy
This study is testing if blood tests can help doctors decide how much radiation therapy patients with HPV-positive throat cancer really need, aiming to reduce side effects while still effectively treating the cancer.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 455 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Mayo Clinic Academic / other |
| Drugs / interventions | chemotherapy, radiation |
| Locations | 3 sites (Scottsdale, Arizona and 2 other locations) |
| Trial ID | NCT05541016 on ClinicalTrials.gov |
What this trial studies
This phase II trial investigates the use of blood-based biomarkers to guide treatment decisions for patients with HPV-positive oropharyngeal squamous cell carcinoma. The study aims to incorporate circulating tumor HPV DNA (ctHPVDNA) alongside clinical and pathologic factors to determine the appropriate intensity of radiation therapy. By identifying patients at low risk of treatment failure, the trial seeks to reduce unnecessary side effects while maintaining effective cancer control. The trial will evaluate progression-free survival rates based on different treatment intensities and the presence of ctHPVDNA. Overall, the goal is to improve treatment outcomes and minimize recurrence rates.
Who should consider this trial
Good fit: Ideal candidates for this study are adults aged 18 and older with histologically confirmed HPV-positive oropharyngeal squamous cell carcinoma who are planning for surgical resection or chemoradiotherapy.
Not a fit: Patients with distant metastases or those who are not eligible for cisplatin treatment may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could lead to more personalized and effective treatment plans for patients with HPV-positive throat cancer, potentially reducing side effects and improving survival rates.
How similar studies have performed: Other studies have shown promise in using biomarkers to tailor cancer treatments, suggesting that this approach may lead to significant advancements in patient care.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * PRE-REGISTRATION (optional): Provide written informed consent * Age \>= 18 years * Histological confirmation of squamous cell carcinoma originating from or suspected to be originating from the oropharynx * Plan for gross total surgical resection via trans oral surgery with curative intent and at least unilateral neck dissection OR chemoradiotherapy with cisplatin. Note: The patient must be cisplatin eligible even if an alternate is used due to drug shortage * Absence of distant metastases on standard diagnostic work-up =\< 16 weeks prior to registration. (Chest CT or PET/CT) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 1 * Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only * Ability to complete questionnaire(s) by themselves or with assistance * Provide written informed consent * Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) * Willing to provide blood samples for correlative research purposes, including anonymous shipment of samples to for NavDx testing Exclusion Criteria: * Any of the following: * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception * Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens * Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)+ * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm * Other active malignancy =\< 5 years prior to registration. EXCEPTIONS: Nonmelanotic skin cancer or carcinoma-in-situ of the cervix, or prostate or localized endometrioid endometrial cancer. NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer * Prior history of radiation therapy to the affected site * Prior systemic chemotherapy in the last 5 years * Contraindication to radiation therapy as determined by the treating team * History of allergic reaction to docetaxel * Receiving any medications or substances which in the opinion of the investigators would interfere with treatment. Examples could include strong inhibitors of cytochrome P450 3A4 (CYP3A4) at oncologist discretion * Severe pre-existing ototoxicity or neuropathy that would, in the opinion of the investigator, preclude the use of cisplatin chemotherapy * cT4 primary tumor * NOTE: Patients with no intermediate risk factors after surgery, low risk patients, as defined by T1, T2, tumors with lymph node less than 3cm, no intermediate or high-risk factors such as lymphatic invasion (LVSI), extranodal extension (ENE), perineural invasion (PNI), positive margin, will be withdrawn from study and be observed per current clinical standard of care. Patients found to be both HPV negative and p16 negative will be withdrawn from study. * Patients found to have HPV non 16 type, or HPV detectability in blood less than \<20tumor tissue modified viral (TTMV) will not be candidates for de-escalation in Groups 1 and 2 and will be treated in Group 3 unless otherwise meeting criteria for low risk. They will receive 60 Gy +/- cisplatin or acceptable alternate regimen when drug shortages of cisplatin exist. If treated primarily with chemoradiation (chemoRT) (Group 4), these patients will not be candidates for de-escalation if TTMV is \< 50 TTMV but can remain on study receiving 70 Gy with all corresponding correlative studies applying * Patients with unknown (radiologic/clinically occult) primaries but neck adenopathy suspected to be HPV associated oropharyngeal carcinoma can be registered to go on study for Groups 1-3. Should after primary resection, no primary tumor be identified, the patient will be withdrawn from study and be treated per institutional standard of care. Group 4 patients must have an identifiable (clinically or radiologically apparent) primary tumor * All treatment primarily, including surgery and chemotherapy will be performed at the enrolling institution
Where this trial is running
Scottsdale, Arizona and 2 other locations
- Mayo Clinic in Arizona — Scottsdale, Arizona, United States (Recruiting)
- Mayo Clinic in Florida — Jacksonville, Florida, United States (Recruiting)
- Mayo Clinic in Rochester — Rochester, Minnesota, United States (Recruiting)
Study contacts
- Principal investigator: David M, Routman, M.D. — Mayo Clinic in Rochester
- Study coordinator: Clinical Trials Referral Office
- Email: mayocliniccancerstudies@mayo.edu
- Phone: 855-776-0015
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.