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Transoral Surgery Followed By Low-Dose or Standard-Dose Radiation Therapy With or Without Chemotherapy in Treating Patients With HPV Positive Stage III-IVA Oropharyngeal Cancer

Primary Purpose

Human Papilloma Virus Infection, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage IVA Squamous Cell Carcinoma of the Oropharynx

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Transoral surgery
intensity-modulated radiation therapy
cisplatin
carboplatin
Sponsored by
ECOG-ACRIN Cancer Research Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Human Papilloma Virus Infection focused on measuring oropharynx cancer, HPV+

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Registration to Surgery (Arm S)

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Patients must have newly diagnosed, histologically or cytologically confirmed squamous cell carcinoma or undifferentiated carcinoma of the oropharynx; patients must have been determined to have resectable oropharyngeal disease; patients with primary tumor or nodal metastasis fixed to the carotid artery, skull base or cervical spine are not eligible
  • Patients must have American Joint Committee on Cancer (AJCC) TNM tumor stage III, IV a, or IV b (with no evidence of distant metastases) as determined by imaging studies (performed < 30 days prior to pre-registration) and complete head and neck exam; the following imaging is required: computed tomography (CT) scan with IV contrast or magnetic resonance imaging (MRI)
  • Patients must have biopsy-proven p16+ oropharynx cancer; the histologic evidence of invasive squamous cell carcinoma may have been obtained from the primary tumor or metastatic lymph node. It is required that patients have a positive p16 IHC (as surrogate for HPV) status from either the primary tumor or metastatic lymph node.
  • Carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory; using p16 antibody obtained from Roche mtm laboratories AG (CINtec, clone E6H4) is recommended
  • Patients with a history of a curatively treated malignancy must be disease-free for at least two years except for carcinoma in situ of cervix and/or non-melanomatous skin cancer
  • Patients with the following within the last 6 months prior to pre-registration must be evaluated by a cardiologist and/or neurologist prior to entry into the study

    • Congestive heart failure > NYHA Class II
    • Cerebrovascular accident (CVA)/transient ischaemic attack (TIA)
    • Unstable angina
    • Myocardial infarction
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelets >= 100,000/mm^3
  • Total bilirubin =< the upper limit of normal (ULN)
  • Calculated creatinine clearance must be > 60 ml/min using the Cockcroft-Gault formula

Registration/Randomization to Step2 - Arms A, B, C and D

  • Histopathologic assessment of surgical pathology must include examination for perineural invasion (PNI) and lymphovascular invasion (LVI) and reported as absent or present; the absence or presence of extracapsular extension (ECE) requires gross and microscopic assessment and is defined to be:

    • Absent (negative or nodal metastasis with smooth/rounded leading edge confined to thickened capsule/pseudocapsule),
    • Present - minimal (tumor extends =< 1 mm beyond the lymph node capsule), or
    • Present - extensive (gross, tumor extends > 1 mm beyond the lymph node capsule (includes soft tissue metastasis)
  • Patient must be stratified/classified into one of the following risk categories (the highest risk feature assessed pathologically will determine the patient's category/treatment arm assignment):

    • Low Risk: T1-T2, N0-N1 AND clear (≥ 3mm) margins, AND no ECE or PNI/LVI
    • High Risk: Any of the following features: one or more positive margin(s) with any T stage, OR "Extensive" (> 1mm) ECE, OR ≥ 5 metastatic lymph nodes (regardless of primary tumor margin status)
    • Intermediate Risk: Any of the following features: one or more "close" (< 3mm) margin(s), OR "Minimal" (≤ 1mm) ECE, OR N2a (1 or more lymph node > 3cm in diameter), OR N2b (2-4 lymph nodes positive, any diameter ≤ 6cm), OR with perineural invasion or lymphovascular invasion.
    • Unknown Risk: Patients found to have N2C or N3 disease on final pathologic analysis are at unknown risk for recurrence, but are not candidates for deintensified adjuvant therapy in this trial. These patients will be treated on Arm C.
    • Patients not categorized into the appropriate risk category will be considered ineligible for the study
  • Patient must be registered/randomized to Step 2 within a maximum of 7 weeks following surgery
  • Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception

Exclusion Criteria:

Registration to Surgery (Arm S)

  • Prior radiation above the clavicles
  • Evidence of extensive or "matted/fixed" pathologic adenopathy on preoperative imaging
  • Women must not be pregnant or breast-feeding due to the teratogenicity of chemotherapy; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Any intercurrent illness likely to interfere with protocol therapy or prevent surgical resection
  • Uncontrolled diabetes, uncontrolled infection despite antibiotics or uncontrolled hypertension within 30 days prior to pre-registration

Sites / Locations

  • University of Alabama at Birmingham Cancer Center
  • Mayo Clinic in Arizona
  • University of Arkansas for Medical Sciences
  • City of Hope Comprehensive Cancer Center
  • UCLA / Jonsson Comprehensive Cancer Center
  • Kaiser Permanente Oakland-Broadway
  • Stanford Cancer Institute
  • UCSF Medical Center-Mount Zion
  • Rocky Mountain Cancer Centers-Boulder
  • Penrose-Saint Francis Healthcare
  • Rocky Mountain Cancer Centers-Penrose
  • Porter Adventist Hospital
  • Yale University
  • University of Miami Sylvester Comprehensive Cancer Center at Deerfield Beach
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
  • Florida Hospital Orlando
  • Emory University Hospital Midtown
  • Emory University/Winship Cancer Institute
  • University of Iowa/Holden Comprehensive Cancer Center
  • University of Kansas Cancer Center
  • University of Kentucky/Markey Cancer Center
  • Greater Baltimore Medical Center
  • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Brigham and Women's Hospital
  • Dana-Farber Cancer Institute
  • Boston Medical Center
  • Henry Ford Hospital
  • Mercy Hospital Springfield
  • Nebraska Methodist Hospital
  • University of Nebraska Medical Center
  • Dartmouth Hitchcock Medical Center
  • University of New Mexico
  • Montefiore Medical Center - Moses Campus
  • Memorial Sloan-Kettering Cancer Center
  • Duke University Medical Center
  • Case Western Reserve University
  • Cleveland Clinic Foundation
  • Ohio State University Comprehensive Cancer Center
  • Providence Portland Medical Center
  • Oregon Health and Science University
  • PinnacleHealth Cancer Center-Community Campus
  • University of Pennsylvania/Abramson Cancer Center
  • Thomas Jefferson University Hospital
  • Fox Chase Cancer Center
  • University of Pittsburgh Cancer Institute (UPCI)
  • Medical University of South Carolina
  • Vanderbilt University/Ingram Cancer Center
  • UT Southwestern/Simmons Cancer Center-Dallas
  • M D Anderson Cancer Center
  • University of Virginia Cancer Center
  • Inova Fairfax Hospital
  • Sentara Cancer Institute at Sentara CarePlex Hospital
  • Sentara Hospitals
  • Sentara Virginia Beach General Hospital
  • University of Washington Medical Center
  • University of Wisconsin Hospital and Clinics
  • Froedtert and the Medical College of Wisconsin
  • Zablocki Veterans Administration Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Arm S (Surgery) then Arm A (Low risk, observation)

Arm S (Surgery) then Arm B (Intermediate risk, low-dose IMRT)

Arm S (Surgery) then Arm C (Intermediate risk, standard-dose IMRT)

Arm S (Surgery) then Arm D (High risk, IMRT, chemotherapy)

Arm Description

Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, low risk patients are under observation.

Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, intermediate risk patients receive low-dose IMRT (50 Gy) QD five days a week for 5 weeks.

Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, intermediate risk patients receive standard-dose IMRT (60 Gy) QD five days a week for 6 weeks.

Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, high risk patients then receive IMRT (66Gy) QD five days a week for 6-7 weeks. Patients also receive cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, 36, and 43 during radiation therapy.

Outcomes

Primary Outcome Measures

Progression-free Survival Rate at 2 Years
Progression-free survival is defined as the time from randomization/assignment of post-surgical treatment to the appearance of lesions, including primary, nodal or new site, or death, whichever occurs first. These patients are considered disease-free after surgery so the appearance of any lesions is counted as progression. Kaplan-Meier estimate was used to characterize progression-free survival rate at 2 years.
Proportion of Patients With Grade III or IV Oropharyngeal Bleeding or Positive Margins
Surgery quality was evaluated based on grade 3-4 bleeding events per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 during surgery and positive margins after surgery. Per CTCAE v5.0, grade 3 = severe and grade 4 = life-threatening. Having grade 3-4 bleeding or positive margins indicates worse outcomes.

Secondary Outcome Measures

Distribution of Histologic Risk Status
Low Risk: T1-T2, N0-N1 AND clear (> 3mm) margins, AND no extranodal extension (ENE) or PNI/LVI. Intermediate Risk: Any of the following features: one or more "close" (< 3mm) margin(s), OR "Minimal" (< 1mm) ENE, OR N2a (1 or more lymph node >3cm in diameter), OR N2b (2-4 lymph nodes positive, any diameter < 6cm), OR with perineural invastion or lymphovascular invasion. High Risk: Any of the following features: one or more positive margin(s) with any T stage, OR "Extensive" (> 1mm) ENE, OR > 5 metastatic lymph nodes (regardless of primary tumor margin status).
Swallowing Function Before Surgery Assessed Using MD Anderson Dysphagia Inventory (MDADI)
The MDADI measures swallowing-related quality of life (QOL) in patients with swallowing dysfunction in a 20-item written questionnaire. It evaluates the patient's physical (P), emotional (E) and functional (F) perceptions of swallowing dysfunction. This instrument has been psychometrically validated in head and neck cancer patients. Two summary scores can be obtained from the MDADI: 1) global and 2) composite. The global scale is a single question, scored individually, to assess the overall impact that swallowing abilities have on quality of life ("my swallowing impacts my day-to-day life"). The composite MDADI score summarizes overall performance on remaining 19-items of the MDADI, as a weighted average of the physical, emotional, and functional subscale questions. This study reports the composite MDADI score. The summary MDADI scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning).
Swallowing Function After Surgery Assessed Using MD Anderson Dysphagia Inventory (MDADI)
The MDADI measures swallowing-related quality of life (QOL) in patients with swallowing dysfunction in a 20-item written questionnaire. It evaluates the patient's physical (P), emotional (E) and functional (F) perceptions of swallowing dysfunction. This instrument has been psychometrically validated in head and neck cancer patients. Two summary scores can be obtained from the MDADI: 1) global and 2) composite. The global scale is a single question, scored individually, to assess the overall impact that swallowing abilities have on quality of life ("my swallowing impacts my day-to-day life"). The composite MDADI score summarizes overall performance on remaining 19-items of the MDADI, as a weighted average of the physical, emotional, and functional subscale questions. This study reports the composite MDADI score. The summary MDADI scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning).
Quality of Life (QOL) at 6 Months After Treatment Assessed by Functional Assessment of Cancer Therapy - Head and Neck Cancer (FACT-HN) Total Score
The FACT-H&N (version 4) consists of a cancer-specific questionnaire, FACT-G, in addition to 12 H&N cancer-specific items (the HN subscale). FACT-G is a 27-item measure that assesses general cancer quality of life. FACT-HN total score ranges between 0 and 148. The higher the score, the better the QOL.

Full Information

First Posted
July 10, 2013
Last Updated
June 15, 2023
Sponsor
ECOG-ACRIN Cancer Research Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01898494
Brief Title
Transoral Surgery Followed By Low-Dose or Standard-Dose Radiation Therapy With or Without Chemotherapy in Treating Patients With HPV Positive Stage III-IVA Oropharyngeal Cancer
Official Title
Phase II Randomized Trial of Transoral Surgical Resection Followed by Low-Dose or Standard-Dose IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 22, 2014 (Actual)
Primary Completion Date
November 30, 2020 (Actual)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ECOG-ACRIN Cancer Research Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This randomized phase II trial studies how well transoral surgery followed by low-dose or standard-dose radiation therapy works in treating patients with human papilloma virus (HPV) positive stage III-IVA oropharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy with chemotherapy may kill any tumor cells that remain after surgery. It is not yet known how much extra treatment needs to be given after surgery.
Detailed Description
PRIMARY OBJECTIVES: I. Accrual, risk distribution, and surgical quality will be used to determine the feasibility of a prospective multi-institutional study of transoral surgery for HPV positive (+) oropharynx cancer followed by risk-adjusted adjuvant therapy. II. To assess the oncologic efficacy following transoral resection and adjuvant therapy in patients determined to be at "intermediate risk" after surgical excision, the 2-year progression free survival (PFS) rate will be examined. SECONDARY OBJECTIVES: I. To estimate the patient distribution with various histologic risk features. II. To assess and compare early and late toxicities associated with transoral surgery (TOS) and the different doses of adjuvant postoperative radiotherapy (PORT). III. To evaluate swallowing function before and after TOS and risk-adjusted adjuvant therapy. IV. To evaluate quality of life (QOL), swallowing perception and performance, voice outcomes, and head and neck symptoms. TERTIARY OBJECTIVES: I. To correlate tumor TP53 mutation and other associated mutation profile with pathologic findings, with PFS and other outcome parameters in patients with resectable HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) after the above treatments. II. To evaluate radiation resistance markers, including excision repair cross complementing 1 (ERCC1) single nucleotide polymorphism and protein expression, and correlate them with treatment efficacy. III. To investigate the usefulness of biomarkers in predicting progression-free survival and biomarkers, including tumor ERCC1, epidermal growth factor receptor (EGFR), plasma cytokine/chemokines, cellular immunity to HPV, and oral HPV deoxyribonucleic acid (DNA). OUTLINE: All patients undergo transoral surgery (TOS) in Step 1. ARM S: Patients undergo transoral resection of the oropharyngeal tumor. Then patients are classified by risk status (low risk, intermediate risk, or high risk) in Step 2 and assigned to the appropriate treatment group. Patients classified as intermediate risk are randomized to arms B or C. ARM A (low risk; observation): Patients receive observation. ARM B (intermediate risk): Patients undergo low-dose (50Gy) intensity modulated radiation therapy (IMRT) once daily (QD) over 25 fractions. ARM C (intermediate risk): Patients undergo standard-dose (60Gy) IMRT QD over 30 fractions. ARM D (high risk): Patients receive IMRT at 66 Gy QD for 33 fractions. Patients also receive cisplatin intravenously (IV) over 60 minutes on days 1, 8, 15, 22, 29, 36, and 43 during radiation therapy. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 year.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Papilloma Virus Infection, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVB Squamous Cell Carcinoma of the Oropharynx
Keywords
oropharynx cancer, HPV+

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
519 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm S (Surgery) then Arm A (Low risk, observation)
Arm Type
Experimental
Arm Description
Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, low risk patients are under observation.
Arm Title
Arm S (Surgery) then Arm B (Intermediate risk, low-dose IMRT)
Arm Type
Experimental
Arm Description
Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, intermediate risk patients receive low-dose IMRT (50 Gy) QD five days a week for 5 weeks.
Arm Title
Arm S (Surgery) then Arm C (Intermediate risk, standard-dose IMRT)
Arm Type
Experimental
Arm Description
Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, intermediate risk patients receive standard-dose IMRT (60 Gy) QD five days a week for 6 weeks.
Arm Title
Arm S (Surgery) then Arm D (High risk, IMRT, chemotherapy)
Arm Type
Experimental
Arm Description
Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, high risk patients then receive IMRT (66Gy) QD five days a week for 6-7 weeks. Patients also receive cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, 36, and 43 during radiation therapy.
Intervention Type
Procedure
Intervention Name(s)
Transoral surgery
Other Intervention Name(s)
TOS
Intervention Description
Undergo transoral surgical resection
Intervention Type
Radiation
Intervention Name(s)
intensity-modulated radiation therapy
Other Intervention Name(s)
IMRT
Intervention Description
Undergo standard-dose or low-dose IMRT
Intervention Type
Drug
Intervention Name(s)
cisplatin
Other Intervention Name(s)
Cis-diaminedichloroplatinum Cis-diaminedichloroplatinum (II), diaminedichloroplatinum, cis-platinum, CDDP, DDP, platinum, Platinol, Platinol-AQ, DACP, NSC 119875 R R
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
carboplatin
Other Intervention Name(s)
CBDCA, JM-8, NSC-241240, Paraplatin
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Progression-free Survival Rate at 2 Years
Description
Progression-free survival is defined as the time from randomization/assignment of post-surgical treatment to the appearance of lesions, including primary, nodal or new site, or death, whichever occurs first. These patients are considered disease-free after surgery so the appearance of any lesions is counted as progression. Kaplan-Meier estimate was used to characterize progression-free survival rate at 2 years.
Time Frame
Assessed every 3 months for 2 years
Title
Proportion of Patients With Grade III or IV Oropharyngeal Bleeding or Positive Margins
Description
Surgery quality was evaluated based on grade 3-4 bleeding events per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 during surgery and positive margins after surgery. Per CTCAE v5.0, grade 3 = severe and grade 4 = life-threatening. Having grade 3-4 bleeding or positive margins indicates worse outcomes.
Time Frame
Assessed during surgery and directly after surgery
Secondary Outcome Measure Information:
Title
Distribution of Histologic Risk Status
Description
Low Risk: T1-T2, N0-N1 AND clear (> 3mm) margins, AND no extranodal extension (ENE) or PNI/LVI. Intermediate Risk: Any of the following features: one or more "close" (< 3mm) margin(s), OR "Minimal" (< 1mm) ENE, OR N2a (1 or more lymph node >3cm in diameter), OR N2b (2-4 lymph nodes positive, any diameter < 6cm), OR with perineural invastion or lymphovascular invasion. High Risk: Any of the following features: one or more positive margin(s) with any T stage, OR "Extensive" (> 1mm) ENE, OR > 5 metastatic lymph nodes (regardless of primary tumor margin status).
Time Frame
Assessed after directly surgery
Title
Swallowing Function Before Surgery Assessed Using MD Anderson Dysphagia Inventory (MDADI)
Description
The MDADI measures swallowing-related quality of life (QOL) in patients with swallowing dysfunction in a 20-item written questionnaire. It evaluates the patient's physical (P), emotional (E) and functional (F) perceptions of swallowing dysfunction. This instrument has been psychometrically validated in head and neck cancer patients. Two summary scores can be obtained from the MDADI: 1) global and 2) composite. The global scale is a single question, scored individually, to assess the overall impact that swallowing abilities have on quality of life ("my swallowing impacts my day-to-day life"). The composite MDADI score summarizes overall performance on remaining 19-items of the MDADI, as a weighted average of the physical, emotional, and functional subscale questions. This study reports the composite MDADI score. The summary MDADI scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning).
Time Frame
Assessed at baseline
Title
Swallowing Function After Surgery Assessed Using MD Anderson Dysphagia Inventory (MDADI)
Description
The MDADI measures swallowing-related quality of life (QOL) in patients with swallowing dysfunction in a 20-item written questionnaire. It evaluates the patient's physical (P), emotional (E) and functional (F) perceptions of swallowing dysfunction. This instrument has been psychometrically validated in head and neck cancer patients. Two summary scores can be obtained from the MDADI: 1) global and 2) composite. The global scale is a single question, scored individually, to assess the overall impact that swallowing abilities have on quality of life ("my swallowing impacts my day-to-day life"). The composite MDADI score summarizes overall performance on remaining 19-items of the MDADI, as a weighted average of the physical, emotional, and functional subscale questions. This study reports the composite MDADI score. The summary MDADI scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning).
Time Frame
Assessed 4-6 weeks after surgery
Title
Quality of Life (QOL) at 6 Months After Treatment Assessed by Functional Assessment of Cancer Therapy - Head and Neck Cancer (FACT-HN) Total Score
Description
The FACT-H&N (version 4) consists of a cancer-specific questionnaire, FACT-G, in addition to 12 H&N cancer-specific items (the HN subscale). FACT-G is a 27-item measure that assesses general cancer quality of life. FACT-HN total score ranges between 0 and 148. The higher the score, the better the QOL.
Time Frame
Assessed at 6 months after treatment
Other Pre-specified Outcome Measures:
Title
Association Between TP53 Mutation and Progression-free Survival
Description
Progression-free survival is defined as the time from registration to the appearance of new metastatic lesions or objective tumor progression or death, whichever occurs first. Kaplan-Meier estimate was used to characterize progression-free survival.
Time Frame
Assessed every 3 months for 2 years, then every 6 months, up to 5 years
Title
Association Between Radiation Resistance Markers and Progression-free Survival
Description
Progression-free survival is defined as the time from registration to the appearance of new metastatic lesions or objective tumor progression or death, whichever occurs first. Kaplan-Meier estimate was used to characterize progression-free survival.
Time Frame
Assessed every 3 months for 2 year, then every 6 months, up to 5 years
Title
Usefulness of Biomarkers in Predicting Progression-free Survival
Description
Progression-free survival is defined as the time from registration to the appearance of new metastatic lesions or objective tumor progression or death, whichever occurs first. Kaplan-Meier estimate was used to characterize progression-free survival.
Time Frame
Assessed every 3 months for 2 years, then every 6 months, up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Registration to Surgery (Arm S) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Patients must have newly diagnosed, histologically or cytologically confirmed squamous cell carcinoma or undifferentiated carcinoma of the oropharynx; patients must have been determined to have resectable oropharyngeal disease; patients with primary tumor or nodal metastasis fixed to the carotid artery, skull base or cervical spine are not eligible Patients must have American Joint Committee on Cancer (AJCC) TNM tumor stage III, IV a, or IV b (with no evidence of distant metastases) as determined by imaging studies (performed < 30 days prior to pre-registration) and complete head and neck exam; the following imaging is required: computed tomography (CT) scan with IV contrast or magnetic resonance imaging (MRI) Patients must have biopsy-proven p16+ oropharynx cancer; the histologic evidence of invasive squamous cell carcinoma may have been obtained from the primary tumor or metastatic lymph node. It is required that patients have a positive p16 IHC (as surrogate for HPV) status from either the primary tumor or metastatic lymph node. Carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory; using p16 antibody obtained from Roche mtm laboratories AG (CINtec, clone E6H4) is recommended Patients with a history of a curatively treated malignancy must be disease-free for at least two years except for carcinoma in situ of cervix and/or non-melanomatous skin cancer Patients with the following within the last 6 months prior to pre-registration must be evaluated by a cardiologist and/or neurologist prior to entry into the study Congestive heart failure > NYHA Class II Cerebrovascular accident (CVA)/transient ischaemic attack (TIA) Unstable angina Myocardial infarction Absolute neutrophil count >= 1,500/mm^3 Platelets >= 100,000/mm^3 Total bilirubin =< the upper limit of normal (ULN) Calculated creatinine clearance must be > 60 ml/min using the Cockcroft-Gault formula Registration/Randomization to Step2 - Arms A, B, C and D Histopathologic assessment of surgical pathology must include examination for perineural invasion (PNI) and lymphovascular invasion (LVI) and reported as absent or present; the absence or presence of extracapsular extension (ECE) requires gross and microscopic assessment and is defined to be: Absent (negative or nodal metastasis with smooth/rounded leading edge confined to thickened capsule/pseudocapsule), Present - minimal (tumor extends =< 1 mm beyond the lymph node capsule), or Present - extensive (gross, tumor extends > 1 mm beyond the lymph node capsule (includes soft tissue metastasis) Patient must be stratified/classified into one of the following risk categories (the highest risk feature assessed pathologically will determine the patient's category/treatment arm assignment): Low Risk: T1-T2, N0-N1 AND clear (≥ 3mm) margins, AND no ECE or PNI/LVI High Risk: Any of the following features: one or more positive margin(s) with any T stage, OR "Extensive" (> 1mm) ECE, OR ≥ 5 metastatic lymph nodes (regardless of primary tumor margin status) Intermediate Risk: Any of the following features: one or more "close" (< 3mm) margin(s), OR "Minimal" (≤ 1mm) ECE, OR N2a (1 or more lymph node > 3cm in diameter), OR N2b (2-4 lymph nodes positive, any diameter ≤ 6cm), OR with perineural invasion or lymphovascular invasion. Unknown Risk: Patients found to have N2C or N3 disease on final pathologic analysis are at unknown risk for recurrence, but are not candidates for deintensified adjuvant therapy in this trial. These patients will be treated on Arm C. Patients not categorized into the appropriate risk category will be considered ineligible for the study Patient must be registered/randomized to Step 2 within a maximum of 7 weeks following surgery Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception Exclusion Criteria: Registration to Surgery (Arm S) Prior radiation above the clavicles Evidence of extensive or "matted/fixed" pathologic adenopathy on preoperative imaging Women must not be pregnant or breast-feeding due to the teratogenicity of chemotherapy; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) Any intercurrent illness likely to interfere with protocol therapy or prevent surgical resection Uncontrolled diabetes, uncontrolled infection despite antibiotics or uncontrolled hypertension within 30 days prior to pre-registration
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Ferris
Organizational Affiliation
ECOG-ACRIN Cancer Research Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
UCLA / Jonsson Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Kaiser Permanente Oakland-Broadway
City
Oakland
State/Province
California
ZIP/Postal Code
94611
Country
United States
Facility Name
Stanford Cancer Institute
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
UCSF Medical Center-Mount Zion
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Rocky Mountain Cancer Centers-Boulder
City
Boulder
State/Province
Colorado
ZIP/Postal Code
80304
Country
United States
Facility Name
Penrose-Saint Francis Healthcare
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
Rocky Mountain Cancer Centers-Penrose
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
Porter Adventist Hospital
City
Denver
State/Province
Colorado
ZIP/Postal Code
80210
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
University of Miami Sylvester Comprehensive Cancer Center at Deerfield Beach
City
Deerfield Beach
State/Province
Florida
ZIP/Postal Code
33442
Country
United States
Facility Name
University of Miami Miller School of Medicine-Sylvester Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Florida Hospital Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Emory University Hospital Midtown
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Emory University/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Iowa/Holden Comprehensive Cancer Center
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Kansas Cancer Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
University of Kentucky/Markey Cancer Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Greater Baltimore Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21204
Country
United States
Facility Name
Johns Hopkins University/Sidney Kimmel Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Boston Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Mercy Hospital Springfield
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65804
Country
United States
Facility Name
Nebraska Methodist Hospital
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
University of New Mexico
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87102
Country
United States
Facility Name
Montefiore Medical Center - Moses Campus
City
Bronx
State/Province
New York
ZIP/Postal Code
10467-2490
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Providence Portland Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
PinnacleHealth Cancer Center-Community Campus
City
Harrisburg
State/Province
Pennsylvania
ZIP/Postal Code
17109
Country
United States
Facility Name
University of Pennsylvania/Abramson Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
University of Pittsburgh Cancer Institute (UPCI)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Vanderbilt University/Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
UT Southwestern/Simmons Cancer Center-Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Virginia Cancer Center
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Inova Fairfax Hospital
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
Sentara Cancer Institute at Sentara CarePlex Hospital
City
Hampton
State/Province
Virginia
ZIP/Postal Code
23666
Country
United States
Facility Name
Sentara Hospitals
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Sentara Virginia Beach General Hospital
City
Virginia Beach
State/Province
Virginia
ZIP/Postal Code
23454
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
University of Wisconsin Hospital and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Froedtert and the Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Zablocki Veterans Administration Medical Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53295
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
Citations:
PubMed Identifier
34699271
Citation
Ferris RL, Flamand Y, Weinstein GS, Li S, Quon H, Mehra R, Garcia JJ, Chung CH, Gillison ML, Duvvuri U, O'Malley BW Jr, Ozer E, Thomas GR, Koch WM, Gross ND, Bell RB, Saba NF, Lango M, Mendez E, Burtness B. Phase II Randomized Trial of Transoral Surgery and Low-Dose Intensity Modulated Radiation Therapy in Resectable p16+ Locally Advanced Oropharynx Cancer: An ECOG-ACRIN Cancer Research Group Trial (E3311). J Clin Oncol. 2022 Jan 10;40(2):138-149. doi: 10.1200/JCO.21.01752. Epub 2021 Oct 26.
Results Reference
result

Learn more about this trial

Transoral Surgery Followed By Low-Dose or Standard-Dose Radiation Therapy With or Without Chemotherapy in Treating Patients With HPV Positive Stage III-IVA Oropharyngeal Cancer

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