We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01898494
Recruitment Status : Active, not recruiting
First Posted : July 12, 2013
Results First Posted : September 28, 2022
Last Update Posted : October 6, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )

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.

Condition or disease Intervention/treatment Phase
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 Procedure: Transoral surgery Radiation: intensity-modulated radiation therapy Drug: cisplatin Drug: carboplatin Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 519 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 9, 2013
Actual Primary Completion Date : November 30, 2020
Estimated Study Completion Date : February 2023

Arm Intervention/treatment
Experimental: Arm S (Surgery) then Arm A (Low risk, observation)
Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, low risk patients are under observation.
Procedure: Transoral surgery
Undergo transoral surgical resection
Other Name: TOS

Experimental: Arm S (Surgery) then Arm B (Intermediate risk, low-dose IMRT)
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.
Procedure: Transoral surgery
Undergo transoral surgical resection
Other Name: TOS

Radiation: intensity-modulated radiation therapy
Undergo standard-dose or low-dose IMRT
Other Name: IMRT

Experimental: Arm S (Surgery) then Arm C (Intermediate risk, standard-dose IMRT)
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.
Procedure: Transoral surgery
Undergo transoral surgical resection
Other Name: TOS

Radiation: intensity-modulated radiation therapy
Undergo standard-dose or low-dose IMRT
Other Name: IMRT

Experimental: Arm S (Surgery) then Arm D (High risk, IMRT, chemotherapy)
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.
Procedure: Transoral surgery
Undergo transoral surgical resection
Other Name: TOS

Radiation: intensity-modulated radiation therapy
Undergo standard-dose or low-dose IMRT
Other Name: IMRT

Drug: cisplatin
Given IV
Other Names:
  • Cis-diaminedichloroplatinum Cis-diaminedichloroplatinum (II)
  • diaminedichloroplatinum
  • cis-platinum
  • CDDP
  • DDP
  • platinum
  • Platinol
  • Platinol-AQ
  • DACP
  • NSC 119875 R R

Drug: carboplatin
Given IV
Other Names:
  • CBDCA
  • JM-8
  • NSC-241240
  • Paraplatin




Primary Outcome Measures :
  1. Progression-free Survival Rate at 2 Years [ Time Frame: Assessed every 3 months for 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.

  2. Proportion of Patients With Grade III or IV Oropharyngeal Bleeding or Positive Margins [ Time Frame: Assessed during surgery and directly after surgery ]

    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 :
  1. Distribution of Histologic Risk Status [ Time Frame: Assessed after directly surgery ]

    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).


  2. Swallowing Function Before Surgery Assessed Using MD Anderson Dysphagia Inventory (MDADI) [ Time Frame: Assessed at baseline ]
    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).

  3. Swallowing Function After Surgery Assessed Using MD Anderson Dysphagia Inventory (MDADI) [ Time Frame: Assessed 4-6 weeks after surgery ]
    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).

  4. Quality of Life (QOL) at 6 Months After Treatment Assessed by Functional Assessment of Cancer Therapy - Head and Neck Cancer (FACT-HN) Total Score [ Time Frame: Assessed at 6 months after treatment ]
    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.


Other Outcome Measures:
  1. Association Between TP53 Mutation and Progression-free Survival [ Time Frame: Assessed every 3 months for 2 years, then every 6 months, up to 5 years ]
    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.

  2. Association Between Radiation Resistance Markers and Progression-free Survival [ Time Frame: Assessed every 3 months for 2 year, then every 6 months, up to 5 years ]
    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.

  3. Usefulness of Biomarkers in Predicting Progression-free Survival [ Time Frame: Assessed every 3 months for 2 years, then every 6 months, up to 5 years ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01898494


Locations
Show Show 58 study locations
Sponsors and Collaborators
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Robert Ferris ECOG-ACRIN Cancer Research Group
  Study Documents (Full-Text)

Documents provided by Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group ):
Publications of Results:
Layout table for additonal information
Responsible Party: ECOG-ACRIN Cancer Research Group
ClinicalTrials.gov Identifier: NCT01898494    
Other Study ID Numbers: E3311
NCI-2013-00814 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
E3311 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
U10CA180820 ( U.S. NIH Grant/Contract )
U10CA021115 ( U.S. NIH Grant/Contract )
First Posted: July 12, 2013    Key Record Dates
Results First Posted: September 28, 2022
Last Update Posted: October 6, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

Layout table for additional information
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
Keywords provided by Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group ):
oropharynx cancer
HPV+
Additional relevant MeSH terms:
Layout table for MeSH terms
Papillomavirus Infections
Carcinoma
Carcinoma, Squamous Cell
Oropharyngeal Neoplasms
Papilloma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Virus Diseases
Infections
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
DNA Virus Infections
Tumor Virus Infections
Cisplatin
Carboplatin
Antineoplastic Agents