Oropharynx Cancer
Conditions
Brief summary
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.
Interventions
DRUGPaclitaxel
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.
DRUGCarboplatin
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.
RADIATIONRadiation Therapy
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.
Sponsors
University of Michigan Rogel Cancer Center
VA Ann Arbor Healthcare System
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Patients With Local Regional Recurrence (LRR) of Disease | 1 Year | 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. |
| Change in Metabolic Tumor Volume 50% (MTV 50%) | 2 months | The change in metabolic tumor volume (MTV)50% at the mid-treatment timepoint will be calculated as percent change from baseline and used as a continuous variable in a Cox model for an outcome of time to LRR. Will also evaluate more non-parametrically, the relation between hazard of LRR and mid-treatment MTV50% using a kernel estimator in a Cox model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patterns of Failure | at 3 months and 2 years | Kaplan-Meier estimate of the percentage of participants who experienced Locoregional relapse versus distant relapse |
| Overall Survival | at 3 months, and 2 Years | Kaplan-Meier estimate of the percentage of participants who are still alive at 3 months and 2 years. |
| Progression- Free Survival | at 3 months and 2 years | Kaplan-Meier estimate of the percentage of participants who are still in progression free survival at 3 months and 2 years |
| Incidence of Toxicity | 1, 3 and 12 months | Toxicity outcomes will be estimated as proportions of patients with available toxicity data at 1, 3 and 12 months. XQ, Xerostomia Questionnaire, is scored on a scale of 0-100 with higher score indicating worse xerostomia. HN, FACT-HN, is scored on a scale of 0-190 with higher score indicating a better quality of life. |
| Detectable Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Participants | from Baseline up to 7 weeks | Median values of ctDNA molecules present throughout the study. The week 6/7 measurement is taken as the first measurement that was available during weeks 6 and 7 to minimize missing data and to account for minor timing deviations in sample collection during weeks 6 and 7 |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichelle Mierzwa, M.D.
University of Michigan Rogel Cancer Center
Participant flow
Pre-assignment details
6 subjects were removed from the trial before being assigned a cohort.
Participants by arm
| Arm | Count |
|---|---|
| Standard Treatment Patients received 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)
Carboplatin: 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.
Radiation Therapy: 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.
Paclitaxel: 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. | 49 |
| De-escalation Treatment Patients initially received 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.
Carboplatin: 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.
Radiation Therapy: 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.
Paclitaxel: 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. | 36 |
| Total | 85 |
Baseline characteristics
| Characteristic | Standard Treatment | De-escalation Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 13 Participants | 31 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 23 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants | 36 Participants | 83 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 47 Participants | 33 Participants | 80 Participants |
| Region of Enrollment United States | 49 participants | 36 participants | 85 participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 43 Participants | 34 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 49 | 1 / 36 |
| other Total, other adverse events | 49 / 49 | 36 / 36 |
| serious Total, serious adverse events | 5 / 49 | 3 / 36 |
Outcome results
Primary
Change in Metabolic Tumor Volume 50% (MTV 50%)
The change in metabolic tumor volume (MTV)50% at the mid-treatment timepoint will be calculated as percent change from baseline and used as a continuous variable in a Cox model for an outcome of time to LRR. Will also evaluate more non-parametrically, the relation between hazard of LRR and mid-treatment MTV50% using a kernel estimator in a Cox model.
Time frame: 2 months
Population: 2 patients were not evaluable
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Treatment | Change in Metabolic Tumor Volume 50% (MTV 50%) | -11.3 percent change from baseline | Standard Deviation 66.7 |
| De-escalation Treatment | Change in Metabolic Tumor Volume 50% (MTV 50%) | -71.1 percent change from baseline | Standard Deviation 16.7 |
Primary
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.
Time frame: 1 Year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Treatment | The Percentage of Patients With Local Regional Recurrence (LRR) of Disease | 2 percentage of participants |
| De-escalation Treatment | The Percentage of Patients With Local Regional Recurrence (LRR) of Disease | 3 percentage of participants |
Secondary
Detectable Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Participants
The proportion of patients in whom ctDNA is detectable will be summarized as a binomial proportion at each timepoint. Additionally, the relation between ctDNA presence or other characteristics and patient outcomes including time to local or distant progression will be assessed by including ctDNA as a covariate in Cox models for local or distant control.
Time frame: 4 weeks
Secondary
Incidence of Toxicity
Toxicity outcomes will be estimated as proportions of patients with available toxicity data at 3, 6 12 and 24 months.
Time frame: 3, 6, 12 and 24 Months
Secondary
Quality of Life Assessed Per the Functional Assessment of Cancer Therapy-Head and Neck (FACTHN)
Quality of life (QOL) outcomes and swallowing study results will be summarized descriptively by timepoint. If there is substantial missingness in the QOL outcomes the study will assess for informative missingness by comparing earlier QOL scores and change in earlier QOL scores between patients missing QOL at later time points (e.g. 1 or 2 years).
Time frame: 2 Years
Secondary
The Proportion of Patients Alive
Time frame: 2 Years