Individualized Adaptive De-escalated Radiotherapy for HPV-related Oropharynx Cancer

Study Overview
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Brief Summary
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This prospective study aims to utilize pre- and mid-treatment PET-CT to guide de-escalation of radiation therapy in HPV-related squamous cell carcinoma of the oropharynx.

Official Title
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A Multi-Center Phase II Trial of Individualized Adaptive De-escalated Radiotherapy Using Pre and Mid-Treatment FDG-PET/CT for HPV-related Oropharynx Cancer

Conditions
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Oropharynx Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Radiation: Radiation Therapy
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have FDG-avid and histologically or cytologically proven squamous cell carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate) that is p16 positive by immunohistochemistry or HPV positive by in situ hybridization. AJCC eighth edition staging stage 1 and stage 2 Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup: History/physical examination, including documentation of weight within 4 weeks prior to registration; FDG-PET/CT scan for staging and RT plan within 4 weeks prior to registration; Zubrod Performance Status (A quantification of the functional status of cancer patients that runs from 0 to 5, with 0 denoting perfect health and 5 death) 0-1 within 4 weeks prior to registration; Age ≥ 18; Able to tolerate PET/CT imaging required to be performed CBC/differential obtained within 4 weeks prior to registration on study, with adequate bone marrow function; Serum creatinine within normal institutional limits or a creatinine clearance ≥ 45 ml/min within 4 weeks prior to registration; Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study. The patient must provide study-specific informed consent prior to study entry. Exclusion Criteria: cT4, cN3 or cM1 disease Matted nodes as determined by review with Neuroradiology Gross total excision of both primary and nodal disease with curative intent; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. In other words, to participate in this protocol, the patient must have clinically or radiographically evident gross disease for which disease response can be assessed. Carcinoma of the neck of unknown primary site origin (even if p16 positive); Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years Any prior therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable if > 3 years prior to study; Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields; Severe, active co-morbidity; Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; Poorly controlled diabetes

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Treatment<br>Patients will receive a single prescription of 70 Gy in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy) | Drug: Carboplatin<br>* AUC=1 weekly during radiation therapy. Carboplatin will be given once a week in combination with paclitaxel (standard treatment), concurrent with radiation therapy. Given IV.<br>Radiation: Radiation Therapy<br>* Patients will initially receive a single prescription of 70 Gy to PTV1 in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). Dose will be reduced to 54Gy to high risk PTV and 43.2Gy to low risk PTV all in 27 fractions for patients who meet pPET-CT and iPET-CT parameters.<br>Drug: Paclitaxel<br>* 30 mg/m2 weekly during radiation therapy. Paclitaxel will be given once a week in combination with carboplatin (standard treatment), concurrent with radiation therapy. Given IV.<br>|
| Experimental: De-escalation Treatment<br>Patients will initially receive a single prescription of 70 Gy in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). If certain parameters are met radiation therapy will be reduced to 54Gy to high risk Planned Target Volume (PTV) and 43.2Gy to low risk PTV all in 27 fractions. | Drug: Carboplatin<br>* AUC=1 weekly during radiation therapy. Carboplatin will be given once a week in combination with paclitaxel (standard treatment), concurrent with radiation therapy. Given IV.<br>Radiation: Radiation Therapy<br>* Patients will initially receive a single prescription of 70 Gy to PTV1 in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). Dose will be reduced to 54Gy to high risk PTV and 43.2Gy to low risk PTV all in 27 fractions for patients who meet pPET-CT and iPET-CT parameters.<br>Drug: Paclitaxel<br>* 30 mg/m2 weekly during radiation therapy. Paclitaxel will be given once a week in combination with carboplatin (standard treatment), concurrent with radiation therapy. Given IV.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of patients with Local Regional Recurrence (LRR) of disease | RECIST (Response Evaluation Criteria In Solid Tumors) will be used to evaluate response and recurrence. All patients will be analyzed together as the goal of the study is to estimate risk of LRR in this patient population treated with this particular strategy in which some patients continue to receive standard therapy while others are de-escalated. Results will also be estimated and reported separately for patients receiving standard or de-escalated therapy. | 1 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients who progress in any location | RECIST (Response Evaluation Criteria In Solid Tumors) will be used to evaluate response. Progression will be defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study or the appearance of one or more new lesions. | 2 Years | 
| The proportion of patients alive |  | 2 Years | 
| Incidence of Toxicity | Toxicity outcomes will be estimated as proportions of patients with available toxicity data at 3, 6 12 and 24 months. | 3, 6, 12 and 24 Months |