Adaptive Treatment De-escalation in Favorable Risk HPV-Positive Oropharyngeal Carcinoma

Launched by NYU LANGONE HEALTH · Jul 11, 2017

Keywords

ClinConnect Summary

This clinical trial is investigating a new approach to treating a specific type of throat cancer called HPV-positive oropharyngeal carcinoma. Researchers want to see if they can safely reduce the amount of chemotherapy and radiation treatment based on how well the tumor responds to the initial treatment. They will specifically look at the tumor's shrinkage and the presence of HPV DNA in the blood during the treatment. The goal is to evaluate how long patients remain free from cancer progression over a two-year period.

To participate in this trial, patients must have a confirmed diagnosis of HPV-positive oropharyngeal squamous cell carcinoma, show signs of the disease at certain stages, and have specific health criteria like a certain level of blood health and kidney function. Patients aged 65 to 74, regardless of gender, can join the study, provided they meet these criteria. Those who qualify will receive treatment and regular check-ups to monitor their response. It’s important to note that patients with a history of certain other cancers, serious health issues, or those who are pregnant cannot participate. This study is currently recruiting participants, aiming to find effective ways to treat this type of cancer while minimizing side effects.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma of the oropharynx, which include the sites tonsil, base of tongue, soft palate, or posterior oropharyngeal wall. Histologic variants will be included (papillary squamous cell carcinoma and basaloid squamous cell carcinoma). Cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx.
• • Patient's tissue must be positive for p16 by immunohistochemical staining (\>70% staining). Fine needle aspiration (FNA) biopsy specimens may be used as the sole diagnostic tissue if formalin-fixed paraffin-embedded cell block material is available for p16 immunohistochemistry.
• • Patients must have detectable circulating plasma HPV DNA at baseline
• * Clinical stage T1-T2, N1-N2b or T3, N1-N2b (AJCC 7th Edition) with no distant metastases based on the following diagnostic workup:
• • Fiberoptic exam with laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 8 weeks prior to registration.
• * One of the following combinations of imaging is required within 8 weeks of registration:
• • 1. Or a CT scan of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast);
• • 2. Or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast)
• • 3. Note: A CT scan of the neck and/or a PET/CT performed for the purposes of radiation planning may serve as both staging and planning tools.
• • Patients must provide their personal smoking history prior to registration. Patients cannot have a cumulative personal smoking history that exceeds 10 pack-years.
• • 1. Number of pack-years = \[Frequency of smoking (number of cigarettes per day) x duration of cigarette smoking (years)\] / 20
• • 2. Note: Twenty cigarettes is considered equivalent to one pack. Cigar and pipe tobacco consumption is not included in calculating lifetime pack-years.
• • Zubrod Performance Status of 0-1 within 8 weeks prior to registration;
• * Adequate hematologic function within 2 weeks prior to registration, defined as follows:
• • Absolute neutrophil count (ANC) ≥ 1,500 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 2 weeks prior to registration, defined as follows:
• • a.Serum creatinine ≤ mg/dl or creatinine clearance (CC) ≥ 50 ml/min determined by 24 hour collection or estimated by Cockcorft-Gault formula: i.CCr male = \[(140 - age) x (wt in kg)\] \[(Serum Cr mg/dl) x (72)\] ii.CCr female = 0.85 x (CrCl male)
• • Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential;
• • Patients who are HIV positive but who have no prior AIDS-defining illness and have CD4 cells of at least 350/mm3 are eligible. HIV-positive patients must not have multi-drug resistant HIV infection or other concurrent AIDS-defining conditions. Patients must not be sero-positive for Hepatitis B (Hepatitis B surface antigen positive or anti-hepatitis B core antigen positive) or sero-positive for Hepatitis C (anti-Hepatitis C antibody positive). However, patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B).
• • The patient must provide study-specific informed consent prior to study entry.
• Exclusion Criteria:
• • Cancers considered to be from an oral cavity site (oral tongue, floor of mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16 positive;
• • Carcinoma of the neck of unknown primary site origin (even if p16 positive);
• • Distant metastasis or adenopathy below the clavicles;
• • Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease.
• • Simultaneous primary cancers or separate bilateral primary tumor sites;
• • Prior invasive malignancy malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible);
• • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable;
• • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
• * Severe, active co-morbidity defined as follows:
• • 1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
• • 2. Transmural myocardial infarction within the last 6 months;
• • 3. Acute bacterial or fungal infection intravenous antibiotics at the time of registration;
• • 4. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration;
• • 5. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol other than those listed in 4.1.10.
• • 6. Acquired immune deficiency syndrome (AIDS) based upon the current CDC definition with immune compromise greater than that noted in section 4.1.12; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immune-compromised patients.
• • Pregnancy; this exclusion is necessary because the treatment in this study may be significantly teratogenic
• • Prior allergic reaction to cisplatin.
• • Exclusion Criteria for MRI: Normal MRI exclusion criteria will apply, including those on the following list. A standard MRI safety form will be used to identify potential conditions warranting exclusion.
• • Electrical implants such as cardiac pacemakers or perfusion pumps
• • Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial heart, valves with steel parts, metal fragments, shrapnel, bullets, tattoos near the eye, or steel implants
• • Ferromagnetic objects such as jewelry or metal clips in clothing
• • Claustrophobia
• • History of seizures
• • Diabetes a.In addition, patients with GFR \< 15 ml/min/1.73m2 or who are on dialysis will not have DCE-MRI scan. These patients will have conventional anatomical MRI without contrast and DW-MRI,