Neoplasms

All Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Oropharyngeal Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Tongue Cancer

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

40 mg/m2 IV (intravenously) weekly for 6 weeks

Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

IMRT 6 weeks

Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy

IMRT 5 weeks

Sue Yom

This randomized phase II trial studies the side effects and how well modestly reduced-dose intensity-modulated radiation therapy (IMRT) with or without cisplatin works in treating patients with oropharyngeal cancer that has spread to other places in the body (advanced). Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether IMRT is more effective with or without cisplatin in treating patients with oropharyngeal cancer.

PRIMARY OBJECTIVES:

-To select the arm(s) achieving a 2-year progression-free survival rate of \>= 85% without unacceptable swallowing toxicity at 1 year.

SECONDARY OBJECTIVES:

* To determine patterns of failure (locoregional relapse versus distant) and survival -(overall and progression-free) at 6 months and 2 years.
* To determine acute toxicity profiles at the end of radiation therapy and at 1 and 6 months.
* To determine late toxicity profiles at 1 and 2 years.
* To determine patient-reported swallowing outcomes at 6 months and 1 and 2 years.
* To determine the predictive value of 12-14 week, post-treatment fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) for locoregional control and progression free survival (PFS) at 2 years.
* To determine the predictive value of blood and tissue biomarkers for disease outcomes at 2 years.
* To determine swallowing recovery per videofluoroscopy imaging at 2 years.

After completion of study treatment, patients are followed at 1 and 3 months then every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Reduced-Dose Intensity-Modulated Radiation Therapy With or Without Cisplatin in Treating Patients With Advanced Oropharyngeal Cancer

A Randomized Phase II Trial for Patients With p16 Positive, Non-Smoking Associated, Locoregionally Advanced Oropharyngeal Cancer

Progression is defined as local, regional, or distant disease progression or death due to any cause. Percentage is estimated using the binomial distribution.

Local-regional failure is defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown \> 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression. Distant metastasis and death due to other causes are considered competing risks. Local-regional failure time is defined as time from randomization to the date of first progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method.

Distant metastasis is defined as distant progression. Local-regional failure and death due to any cause are considered competing risks. Distant metastasis time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method.

Overall survival time is defined as time from randomization to the date of death or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method.

Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.

The MDADI is a 20-item tool with each item scored as Strongly agree; Agree; No opinion; Disagree; or Strongly disagree. There is 1 global item (G1), 6 emotional subscale items (E2-E7), 5 functional subscale items (F1-F5), and 8 physical subscale items (P1-P8). For all items except E7 and F2, Strongly agree corresponds to a score of 1, Agree 2, No opinion 3, Disagree 4, and Strongly disagree 5. For E7 and F2, the scores are reversed; these 2 items are rescored to match the others before calculating summary scores. The composite (total) score is the mean of the 19 items (other than G1) X 20. Composite scores range from 20 to 100 with higher scores indicating less dysphagia.

NPV is the percentage of participants alive and failure-free at 2 years among those with a negative post-treatment scan, as evaluated by central review. Negative scan determined as follows: primary site, right neck, left neck evaluated using a 5-point ordinal scale: 1-Definite complete metabolic response (CMR), 2-Likely CMR, 3-Likely inflammatory, 4-Likely residual metabolic disease (RMD), and 5-Definite RMD. 'Negative'= 1 or 2, 'Indeterminate'=3, 'Positive' = 4 or 5. 'Negative' for all three evaluation sites = overall score of 'Negative.' Progression (failure) is defined as local, regional, or distant disease progression (PR) or any death. Local-regional progression (failure) is defined as local or regional PR, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown \> 20 weeks post RT, death due to study cancer or unknown causes without documented PR. The protocol specified that both arms would be combined for analysis.

With a two-sided type error rate of 5% and based on chi-squared test for proportions, there is a greater than 99% power to detect HPV DNA detection rate of 65% and 95% between the 2 groups (n=140 in each arm). The rate of detection for each group will be summarized based on binomial distributions and a 95% confidence intervals (CI) will be provided.

With a two-sided type error rate of 5% and based on paired t test for means, there is 99% power to detect HPV DNA rate decline of 0.375 (effect size) within each arm (n=140). The HPV DNA rate for each group will be summarized using means and standard deviations.

Correlation between HPV DNA copy number and the nodal metabolic volume will be calculated using Spearman's correlation coefficient and R2, and the corresponding 95% CI will be provided.

Univariable and multivariable cause specific analysis will be performed using the Cox proportional hazards model for rate of relapse.

National Cancer Institute (NCI)

NRG Oncology

Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks

IMRT 6 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

IMRT 6 Weeks + Cisplatin

IMRT 5 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy

IMRT 5 Weeks

Total

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Zubrod performance status

Smoking history as measured in pack-years, calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked.

Smoking history (pack years)

Primary tumor site

Tumor stage per the American Joint Committee on Cancer (AJCC) 7th ed. refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further divided to provide more detail, such as T3a and T3b.

T stage, clinical

Regional lymph nodes staging per American Joint Committee on Cancer (AJCC) 7th ed. refers to the number and/or extent of spread of lymph nodes that contain cancer. The higher the number after the N, the greater the involvement of regional lymph nodes.

N stage, clinical

Radiation therapy plan included unilateral or bilateral radiation to the neck, as provided by the treating site at stratification.

Radiation Therapy (RT) planning (as stratified)

Radiation therapy plan included unilateral or bilateral radiation to the neck, as provided by central review by the study radiation oncologist.

RT planning (per central review)

Wendy Seiferheld

Assuming a binomial distribution, 140 eligible patients per arm were required for 80% power and 1-sided type I error rate of 10% to test the null hypothesis of 2-year progression-free survival (PFS) rate ≤ 85% against the alternative hypothesis of \> 85% with a binomial test. The arms are not compared to each other; they are each tested separately against the null hypothesis.

Assuming a binomial distribution, 140 eligible patients per arm were required for 80% power and 1-sided type I error rate of 10% to test the null hypothesis of 2-year PFS rate ≤ 85% against the alternative hypothesis of \> 85% with a binomial test. The arms are not compared to each other; they are each tested separately against the null hypothesis.

IMRT 6 Weeks + Cisplatin (Arm 1)

IMRT 5 Weeks (Arm 2)

Two-year data was available for 147/157 (Arm 1) and 145/149 (Arm 2) randomized and eligible participants.

Percentage of Participants Alive Without Progression at Two Years (Progression-free Survival)

Six months

Two years

Percentage of Participants With Local-regional Failure

Percentage of Participants With Distant Metastasis

Percentage of Participants Alive

End of RT

1 month post-RT

6 months post-RT

1 year post-RT

2 years post-RT

Randomized and eligible participants who started study treatment. Adverse event data was not available for all participants at each time point.

Percentage of Participants With Grade 3+ Adverse Events

Randomized and eligible participants. Questionnaires were not completed by all participants. 121 Arm 1 and 106 Arm 2 participants had one year post-RT data.

Mean One-year Total MD Anderson Dysphagia Inventory (MDADI) Score (Patient-reported Swallowing Outcome)

Progression-free survival: The null hypothesis of negative predictive value ≤ 90% was tested against the alternative of \> 90% with a 1-sided binomial test at the 0.10 level.

Local-regional control: The null hypothesis of negative predictive value ≤ 90% was tested against the alternative of \> 90% with a 1-sided binomial test at the 0.10 level.

Progression-free Survival

Local-regional failure

IMRT 6 Weeks + Cisplatin arm: Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks; Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy.

IMRT 5 weeks arm: Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy

Both Arms Combined

Randomized and eligible participants with negative post-treatment PET

Negative Predictive Value (NPV) of Post-treatment FDG-PET/CT Scan [Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT)] for Progression-free Survival and Local-regional Control at Two Years

Spots Global Cancer Trial Database for imrt 5 weeks

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