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Adaptive Treatment De-escalation in Favorable Risk HPV-Positive Oropharyngeal Carcinoma Fase 2 120 Adaptief ontwerp
Adaptive De-escalation of Radiation Therapy Dose in HPV-Positive Oropharyngeal Carcinoma (ART) Demonstrating Favorable Mid-Treatment Response
- 17-00330
| Deelnemersgroep/Studiearm | Interventie/Behandeling |
|---|---|
ExperimenteelArm 1: Dose de-escalation (6 weeks) 26 participants demonstrating a favorable response defined as \>40% nodal shrinkage were eligible to receive the de-escalated treatment regimen (6 doses of weekly cisplatinum with 6 weeks of radiation to a total dose of 60Gy).
This arm is closed and has been replaced with Arm 3. | Dose-Deescalated Treatment Intensity-modulated radiation therapy (IMRT) is an advanced type of radiation therapy used to treat cancer and noncancerous tumors. IMRT uses advanced technology to manipulate photon and proton beams of radiation to conform to the shape of a tumor. Patients will be treated with intensity-modulated radiation therapy (IMRT) with megavoltage photons Cisplatinum Standard of care chemotherapy |
Actieve comparatorArm 2: Standard radiation therapy + cisplatinum (7 weeks) Participants will receive standard radiation therapy and cisplatinum for 7 weeks. | Standard Radiation Treatment An interval scan at 4 weeks to assess for a good response defined as \>40% nodal shrinkage will stratify patients into receiving standard treatment (≤40% nodal shrinkage) or a dose-deescalated treatment regimen (\>40% nodal shrinkage). Those with nodal shrinkage and clearance of circulating plasma HPV DNA shall undergo further treatment de-escalation. Dose-Deescalated Treatment Intensity-modulated radiation therapy (IMRT) is an advanced type of radiation therapy used to treat cancer and noncancerous tumors. IMRT uses advanced technology to manipulate photon and proton beams of radiation to conform to the shape of a tumor. Patients will be treated with intensity-modulated radiation therapy (IMRT) with megavoltage photons Cisplatinum Standard of care chemotherapy |
ExperimenteelArm 3: Dose de-escalation (6 weeks) For participants who achieve (a) rapid nodal shrinkage on interval CT scan but slow / unknown ctHPV DNA clearance OR (b) slow nodal shrinkage on interval CT scan but rapid ctHPV DNA clearance at week 4, radiation treatment will be de-escalated to a total dose of 60Gy/6 weeks with 6 doses of weekly (cisplatinum).
This arm replaced Arm 1. | Dose-Deescalated Treatment Intensity-modulated radiation therapy (IMRT) is an advanced type of radiation therapy used to treat cancer and noncancerous tumors. IMRT uses advanced technology to manipulate photon and proton beams of radiation to conform to the shape of a tumor. Patients will be treated with intensity-modulated radiation therapy (IMRT) with megavoltage photons Cisplatinum Standard of care chemotherapy |
ExperimenteelArm 4: Dose de-escalation (5 weeks) For participants who achieve both a favorable nodal response (\>40%) on interval CT scan as well as rapid ctHPV DNA clearance at week 4, radiation treatment will be further de-escalated to a total dose of 50 Gy/5 weeks with 5 doses of weekly cisplatinum). | Dose-Deescalated Treatment Intensity-modulated radiation therapy (IMRT) is an advanced type of radiation therapy used to treat cancer and noncancerous tumors. IMRT uses advanced technology to manipulate photon and proton beams of radiation to conform to the shape of a tumor. Patients will be treated with intensity-modulated radiation therapy (IMRT) with megavoltage photons Cisplatinum Standard of care chemotherapy |
| Uitkomstmaat | Beschrijving van de uitkomstmaat | Tijdsbestek |
|---|---|---|
Progression-free survival at 2 years | The non-inferiority (NI) analysis will be conducted on the pooled de-escalated cohort (Arms 3+4 combined) to evaluate whether the 2-year PFS is acceptable relative to the historical benchmark. For Arm 3 and Arm 4 separately, Kaplan-Meier curves and 2-year PFS estimates with 95% confidence intervals will be provided. Patients who do not experience progression of disease and have not died will be censored on the date of last follow up. | 2 Years |
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.
If the primary site is biopsied, 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 not available for p16 immunohistochemistry.
Patients must have detectable HPV ctDNA Score Report at Screening or have a detectable baseline HPV ctDNA Score Report (Naveris test) if no primary site is biopsied. Must have detectable screening plasma HPV DNA (also referred to as ctHPV DNA).
Clinical stage T1-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:
- CT scan of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast);
- Or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast)
- 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.
- Number of pack-years = \[Frequency of smoking (number of cigarettes per day) x duration of cigarette smoking (years)\] / 20
- 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 ≤ 1.5 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.
Missing or undetectable baseline plasma HPV DNA level
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 (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:
- 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 intravenous antibiotics at the time of registration;
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration;
- 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.
- 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
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.
NYU Langone HealthNew York