- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05388773
Transoral Surgical Resection Followed by De-escalated Adjuvant IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer
Phase II Trial of Transoral Surgical Resection Followed by De-escalated Adjuvant IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Samantha Demko, RN, BSN
- Phone Number: 412-623-1400
- Email: albesl@upmc.edu
Study Contact Backup
- Name: Brieana Marino, MS
- Phone Number: 412-647-8258
- Email: rowlesbm@upmc.edu
Study Locations
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15232
- Recruiting
- UPMC Hillman Cancer Center
-
Contact:
- Samantha Demko, RN, BSN
- Phone Number: 412-623-1400
- Email: albesl@upmc.edu
-
Contact:
- Brieana Marino, MS
- Phone Number: 412-647-8258
- Email: rowlesbm@upmc.edu
-
Principal Investigator:
- Heath D Skinner, MD, PhD
-
Sub-Investigator:
- Umamaheswar Duvvuri, MD, PhD
-
Sub-Investigator:
- Dan Zandberg, MD
-
Sub-Investigator:
- Simon Chiosea, MD
-
Sub-Investigator:
- Robert L Ferris, MD, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- ECOG performance status of 0 or 1 or Karnofsky score 80-100.
- Newly diagnosed, histologically or cytologically confirmed SCC or undifferentiated carcinoma of the oropharynx and resectable oropharyngeal disease.
- Patients must be deemed eligible for a TOS procedure with no evidence of distant metastasis as determined by imaging studies.
- 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.
- Carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a CLIA approved laboratory.
- No prior radiation above the clavicles.
- 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, melanoma in-situ (if fully resected), and/or non-melanomatous skin cancer.
- Patients with congestive heart failure > NYHA Class II, CVA/TIA, unstable angina, or myocardial infarction within the last 6 months prior to registration must be evaluated by a cardiologist and/or neurologist.
- Acceptable renal and hepatic function within 4 weeks prior to registration as predefined.
Exclusion Criteria:
- No 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.
- No intercurrent illness likely to interfere with protocol therapy or prevent surgical resection.
- No uncontrolled diabetes, infection despite antibiotics, or hypertension within 30 days prior to registration.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm S (Low Risk)
Low risk patients are defined as T1-T2 AND 0 or 1 metastatic lymph nodes AND <3 cm AND clear (≥3mm) margins AND no extracapsular extension (ECE) AND no perineural invasion AND no lymphovascular invasion. Patients will undergo transoral surgical resection of the oropharyngeal tumor. |
Correlative studies
Transoral surgical resection of tumor(s).
Ancillary studies.
Other Names:
|
Experimental: Arm RT (Intermediate Risk)
Intermediate risk patients are defined as having any of the following features: One or more close (<3mm) margins, OR "minimal" ≤1 mm ECE OR 1 or more metastatic lymph nodes >3 cm in diameter OR 2-4 lymph nodes positive (≤ 6 cm in diameter), OR perineural invasion OR lymphovascular invasion Patients will undergo transoral surgical resection of the oropharyngeal tumor. Following surgery, patients will receive low-dose IMRT five times a week for 3 weeks. |
Correlative studies
Transoral surgical resection of tumor(s).
Ancillary studies.
Other Names:
Low-dose IMRT
Other Names:
|
Experimental: Arm CRT (High Risk)
High risk patients are defined as having any of the following features: One or more positive margins OR >1 mm ECE OR ≥ 5 metastatic lymph nodes. Patients will undergo transoral surgical resection of the oropharyngeal tumor. Following surgery, patients will receive low-dose IMRT six times a week and a weekly chemotherapy infusion (cisplatin or carboplatin) during radiation therapy. Patients will receive 2 Gy/fraction, 6 fractions per week with at least a 6-hour interfraction interval between each treatment:
|
Correlative studies
Given IV
Other Names:
Given IV.
Other Names:
Transoral surgical resection of tumor(s).
Ancillary studies.
Other Names:
Low-dose IMRT
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Recurrence-Free Survival (RFS)
Time Frame: Up to 2 years (for cohort)
|
Time to recurrence, defined as local and/or regional progression (identification of disease growth that is present within the area in which it was first located) and/or distant metastasis (identification of disease growth that is present in area(s) distant to that previously located).
Local progression is defined as progression at the primary tumor site.
Regional progression is defined as progression in the draining lymphatics (typically the cervical, retropharyngeal/retrostyloid and supraclavicular lymph nodes).
Distant progression is defined as tumor recurrence in one or more non-local and non-regional sites (e.g., bone, lung, liver, etc.).
Recurrent malignancy will be determined based on clinical exam and imaging findings.
Patients who are disease-free but who die from other causes will be censored.
|
Up to 2 years (for cohort)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Loco-regional control (at 1 year)
Time Frame: Up to 1 year
|
Loco-regional control will be evaluated based on the percentage of patients without recurrence (identification of disease growth) in the primary site or regional lymphatics based on imaging and/or clinical exam.
|
Up to 1 year
|
Loco-regional control (at 2 years)
Time Frame: Up to 2 year
|
Loco-regional control will be evaluated based on the percentage of patients without recurrence (identification of disease growth) in the primary site or regional lymphatics based on imaging and/or clinical exam.
|
Up to 2 year
|
Time to distant metastasis (at 1 year)
Time Frame: Up to 1 year
|
Percentage of patients with distant metastasis (identification of disease growth that is present in area(s) distant to that previously located) evident on imaging and/or clinical exam.
Distant metastasis is defined as tumor recurrence in one or more non-local (at the primary tumor) and non-regional (draining lymphatic) sites such as bone, lung, liver, etc.
|
Up to 1 year
|
Time to distant metastasis (at 2 years)
Time Frame: Up to 2 years
|
Percentage of patients with distant metastasis (identification of disease growth that is present in area(s) distant to that previously located) evident on imaging and/or clinical exam.
Distant metastasis is defined as tumor recurrence in one or more non-local (at the primary tumor) and non-regional (draining lymphatic) sites such as bone, lung, liver, etc.
|
Up to 2 years
|
Overall survival at 1 year
Time Frame: Up to 1 year
|
Overall survival will be measured as the time from start of treatment to death from any cause.
|
Up to 1 year
|
Overall survival at 2 years
Time Frame: Up to 2 years
|
Overall survival will be measured as the time from start of treatment to death from any cause.
|
Up to 2 years
|
Distribution of patients based on histologic risk features
Time Frame: Up to 3 years
|
The percentage of total patients enrolled in the study allocated to low (Arm S), intermediate (Arm RT) and high risk (Arm CRT) groups.
Histologic risk features are defined as follows: Low risk (ARM S) - T1-T2 AND 0 or 1 metastatic lymph nodes AND <3 cm AND clear (≥3mm) margins AND no extracapsular extension (ECE) AND no perineural invasion AND no lymphovascular invasion; Intermediate risk (ARM RT) - Any of the following features: One or more close (<3mm) margins, OR "minimal" ≤1 mm ECE OR 1 or more metastatic lymph nodes >3 cm in diameter OR 2-4 lymph nodes positive (≤ 6 cm in diameter), OR perineural invasion OR lymphovascular invasion; High risk (ARM CRT) - Any of the following features: One or more positive margins OR >1 mm ECE OR ≥ 5 metastatic lymph nodes.
|
Up to 3 years
|
Assessment of PEG tube dependence
Time Frame: At 1 year (post treatment)
|
The percentage of patients that have a feeding tube, by Arm, for the low (Arm S), intermediate (Arm RT) and high risk (Arm CRT) groups following treatment with transoral resection and adjuvant therapy.
|
At 1 year (post treatment)
|
Adverse Events Related to Treatment
Time Frame: Up to 5 years
|
Number of patients experiencing toxicities related to study treatment per Common Terminology Criteria for Adverse Events (CTCAE v5.0) determined at each follow-up summarized by frequency and grade.
|
Up to 5 years
|
Quality of Life via FACT-HN
Time Frame: Baseline (before treatment), at 4-8 weeks post-surgery, at 3 months, 6 months, 1 year, up to 2 years following treatment
|
FACT-HN is a self-administered questionnaire.
Item responses are on a Likert scale score ranging from 0 to 4. Individual responses are summed to compute subscale scores, and the subscales to compute overall total scores.
FACT-HN includes 2 parts - FACT-G and FACT-HN.
The basic FACT-G (general) is comprised of 27 items, with four subscales including Physical Well-Being (score = 0-28), Social/Family Well-Being (score= 0-28), Emotional Well-Being (score = 0-24), and Functional Well-Being, (score = 0-28), for a total score min/max = 0-108.
The FACT-HN is comprised of 12 head and neck specific items (0-48).
Thus, the overall total possible score range is 0-156.
Analysis will include the FACT Head & Neck Trial Outcome Index, a composite score which includes only physical, functional, and FACT-HN, thus, scores range from 0-104.
Higher scores indicate better Quality of Life.
|
Baseline (before treatment), at 4-8 weeks post-surgery, at 3 months, 6 months, 1 year, up to 2 years following treatment
|
MD Anderson Symptom Inventory-Head & Neck (MDASI-HN)
Time Frame: Baseline (before treatment), at 4-8 weeks post-surgery, at 3 months, 6 months, up to 2 years following treatment
|
Patient-reported swallowing perception and performance using MDASI-HN measures treatment related symptom burden in head and neck cancer patients.
The 20-item MDASI measures both severity and burden of symptoms and their effect on patients' daily activities, using a numeric rating scale of 0-10.
This instrument includes 13 core symptoms and 9 head and neck specific items.
Higher scores indicate superior perception of function.
|
Baseline (before treatment), at 4-8 weeks post-surgery, at 3 months, 6 months, up to 2 years following treatment
|
Modified Barium Swallow (MBS) rating
Time Frame: Before treatment, at 4-8 weeks post-surgery, 6 months and 24 months following treatment
|
Three swallowing outcomes will be rated by the SLP conducting the MBS study and reported by research staff: 1) laryngeal penetration (yes, no); 2) aspiration (no, sensate, silent), and 3) pharyngeal residue (no, < 50%, > 50%).
These have been selected as universal items generally reported by swallowing clinicians that have been shown to significantly predict pneumonia in patients with oropharyngeal cancers.
Prevalence of these dysphagia endpoints will be estimated at each time point.
|
Before treatment, at 4-8 weeks post-surgery, 6 months and 24 months following treatment
|
Voice outcomes
Time Frame: Baseline (before treatment), at 4-8 weeks post-surgery, at 1 year, up to 2 years following treatment
|
Patient-reported voice outcomes will be assessed using the Voice Handicap Index-10 (VHI-10) survey.
The VHI-10 is a patient self-assessment instrument that quantifies patients' perception of their voice handicap.
It evaluates patient's physical (P), emotional (E), and functional (F) perceptions of voice and has shown to be highly reliable for internal consistency and test-retest stability.
The VHI-10 utilizes a 10-item questionnaire in which the patient circles the response that most accurately reflects his or her own experience on a linear scale (from "never" to "always").
"Always" response is scored 4 points, a "Never" response is scored 0. The remaining options are scored between 1 and 3 points.
The tallied number of points for each of the subscales is computed to a total composite score.
The patient's values are compared to published norms.
|
Baseline (before treatment), at 4-8 weeks post-surgery, at 1 year, up to 2 years following treatment
|
Performance Status Scale (PSS-HN)
Time Frame: Baseline (before treatment), at 4-8 weeks post-surgery, at 3 months, 6 months, 1 year, up to 2 years following treatment
|
The Performance Status Scale (PSS-HN) is a clinician-rated instrument consisting of 3 questions: normalcy of diet, public eating/swallowing, and understandability of speech subscales in patients with head and neck cancer.
Each subscale is rated from 0 to 100, with higher scores indicating better performance.
|
Baseline (before treatment), at 4-8 weeks post-surgery, at 3 months, 6 months, 1 year, up to 2 years following treatment
|
MD Anderson Dysphagia Inventory (MDADI)
Time Frame: Baseline (before treatment), at 4-8 weeks post-surgery, at 1 year, up to 2 years following treatment
|
Patient-reported swallowing-related quality of life will be measured using the MD Anderson Dysphagia Inventory (MDADI).
It evaluates the patient's physical (P), emotional (E) and functional (F) perceptions of swallowing dysfunction.
The MDADI is a 20-item questionnaire in which the patient circles the response that best reflects their experience in the past week on a 5-point Likert Scale with answers ranging from "Strongly Agree" (scored as 1 point on all questions except E7 and F2, where it is scored as 5 points) to "Strongly Disagree" (scored as 5 points on all questions except E7 and F2, where it is scored as 1 point).
Scores for individual questions are summed and averaged to obtain a composite score ranging from 20 (extremely low swallow functioning) to 100 (high swallow functioning).
|
Baseline (before treatment), at 4-8 weeks post-surgery, at 1 year, up to 2 years following treatment
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Heath Skinner, MD, PhD, UPMC Hillman Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- Cisplatin
- Carboplatin
- Antineoplastic Agents
- Head and Neck Neoplasms
- DNA Virus Infections
- Tumor Virus Infections
- Papillomavirus Infections
- Neoplasms, Glandular and Epithelial
- Otorhinolaryngologic Diseases
- Oropharyngeal Neoplasms
- Intensity Modulated Radiotherapy
- Stomatognathic Diseases
- Carcinoma, Squamous Cell
- Pharyngeal Diseases
- Pharyngeal Neoplasms
- Otorhinolaryngologic Neoplasms
- Transoral Surgery
- Papilloma
Additional Relevant MeSH Terms
Other Study ID Numbers
- HCC 22-030
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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