- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01612351
Multimodality Risk Adapted Tx Including Induction Chemo for SCCHN Amenable to Transoral Surgery
September 13, 2023 updated by: UNC Lineberger Comprehensive Cancer Center
Multimodality Risk Adapted Therapy Including Carboplatin/Paclitaxel/Lapatinib as Induction for Squamous Cell Carcinoma of the Head and Neck Amenable to Transoral Surgical Approaches
The purpose of this study is to see if a three method risk adapted design using induction chemotherapy, transoral surgery and radiation chemotherapy will lessen toxic effects and make treatment of squamous cell carcinoma of the head and neck (SCCHN) better.
Study Overview
Status
Active, not recruiting
Detailed Description
This is a single-arm non-randomized two-stage phase II trial in previously untreated patients with squamous cell carcinoma of the head and neck (SCCHN) arising in the oral cavity, oropharynx, or supraglottic larynx amenable to a transoral surgical approach.
Treatment will consist of 3 parts: neoadjuvant induction with weekly carboplatin and paclitaxel in combination with daily lapatinib for 6 weeks (PART 1) prior to transoral surgery (PART 2).
Post-operative treatment (PART 3) will vary depending on the risk category assigned to the patient following surgery as follows: no further treatment or treatment limited to involved field radiation (low risk), ipsilateral radiation concurrent with weekly chemotherapy ( medium risk); or cisplatin every 3 weeks and daily lapatinib concurrent with bilateral radiation (high risk).
Study Type
Interventional
Enrollment (Actual)
40
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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North Carolina
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Chapel Hill, North Carolina, United States, 27599
- The University of North Carolina at Chapel Hill
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Previously untreated, histologically proven primary squamous cell carcinoma arising in the oral cavity, oropharynx, or supraglottic larynx, and amenable to transoral approach
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Appendix C)
- Measurable disease as per Response Evaluation Criteria In Solid Tumors (RECIST1.1)
- Age ≥18 years
- Adequate bone marrow function as demonstrated by: Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3; Hgb > 10 g/dL (use of transfusion to reach this threshold prior to study initiation is acceptable); Platelet count ≥ 100,000/mm3
- Adequate hepatic and renal function as demonstrated by: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN); Total serum bilirubin ≤1.5 mg/dL; Creatinine clearance (CrCL) ≥ 40ml/min as measured via Cockcroft-Gault
- Left ventricular ejection fraction (LVEF) must be > the lower limit of normal (LLN) per institutional standards by either echocardiography or radionuclide-based multiple gated acquisition (MUGA)
- Negative serum human chorionic gonadotropin (β-hCG) pregnancy test within 72 hours of day 1 of induction chemotherapy in women of child-bearing potential
- All males and females of childbearing potential must agree to use adequate contraception during the study. Adequate contraception is defined as any medically recommended method (or combination of methods) as per standard of care. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy
- Signed an institutional review board (IRB)-approved informed consent document for this protocol.
Exclusion Criteria:
- tumor 1-node 0 (T1N0) disease or tumor 2-node 0 (T2N0) disease
- Any metastatic disease
- Not considered eligible for any of the chemotherapy agents included in the induction regimen.
- Current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
- Major surgery within 3 weeks prior to day 1 of study treatment from which the patient has not completely recovered
- Current use of a prohibited medication or requires any of these medications during treatment with lapatinib prior to study entry
- Receiving any investigational agent currently, or within 2 weeks of Day 1 of treatment on this study
- Active, serious infection, medical, or psychiatric condition that would represent an inappropriate risk to the patient or would likely compromise achievement of the primary study objective, including unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction ≤ 6 months prior to study entry
- Adequate swallowing function or gastric-tube for drug administration. Of note, lapatinib can be administered via G-tube in a slurry for patients who cannot swallow
- Other prior or concomitant malignancies with the exception of: Non-melanoma skin cancer; In-situ malignancy; Low-risk prostate cancer after curative therapy; Other cancer for which the patient has been disease free for ≥ 3 years
- Pregnant or lactating women, or adults of reproductive potential who do not agree to use adequate contraception during study treatment (see definition of adequate contraception
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Non-Randomized Single-Arm
All participants will receive induction chemotherapy and transoral surgery.
Following surgery, participants will be stratified into a risk category (low, medium, or high).
Subjects in the low risk category will receive no further treatment after their transoral surgery.
Subjects in the medium risk category will receive ipsilateral radiation concurrent with weekly cisplatin, and subjects in the high risk category will receive cisplatin every three weeks with concurrent bilateral radiation.
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Weekly carboplatin given intravenously for 6 weeks during induction chemotherapy.
Other Names:
Weekly paclitaxel given intravenously prior to carboplatin infusion for 6 weeks during induction chemotherapy.
Other Names:
Lapatinib (1000mg) taken by mouth once a day either one hour before or one hour after a meal for 6 weeks during induction chemotherapy.
Participants deemed high risk following transoral surgery will additionally take lapatinib daily concurrently with their chemoradiation therapy.
Other Names:
Weekly cisplatin given intravenously for 6 weeks concurrent with ipsilateral radiation.
Alternative regimens may be substituted for cisplatin in patients who are not candidates for cisplatin at the discretion of the investigator.
If carboplatin is used, a maximum of 125 mL/min must be used, as per standard of care.
Other Names:
Cisplatin given once every 3 week cycle intravenously for 5-7 weeks concurrent with bilateral radiation and daily lapatinib.
Alternative regimens may be substituted for cisplatin in patients who are not candidates for cisplatin at the discretion of the investigator.
If carboplatin is used, a maximum of 125 mL/min must be used, as per standard of care.
Other Names:
After transoral surgery, subjects deemed medium risk will receive ipsilateral radiation as per standard of care 5 days/week for 6 weeks concurrent with weekly cisplatin.
Other Names:
After transoral surgery, subjects deemed high risk will receive bilateral radiation as per standard of care 5 days/week for 5-7 weeks concurrent with cisplatin every 3 weeks and daily lapatinib.
Other Names:
Transoral resection by robotic or microscopic approach, which will be at the discretion of the treating surgeon.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate
Time Frame: 11 weeks
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Evaluation of target lesions through tumor imaging (CT scan, MRI, and/or chest x-ray) at 3-5 weeks post induction chemotherapy.
Overall response rate will be based on RECIST criteria.
Overall response rate (ORR) is defined as the number of patients who have a partial or complete response to therapy.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
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11 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Feasibility of 3 Part Therapy
Time Frame: 2 years
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Percentage of patients successfully completing 3 part therapy will be used to assess the feasibility of 3 part therapy consisting of induction chemotherapy, surgery, and risk-adapted use of chemoradiation.
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2 years
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Number of Patients Who Decreased in Risk Level Post Induction Chemotherapy.
Time Frame: 11 weeks
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Number of patients who no longer need radiation (have decreases in risk level post induction therapy).
Estimations of Risk level pre-induction will be based on physical examination and imaging, post-induction risk level will be determined based on pathologic evaluation or surgical specimen.
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11 weeks
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Overall Survival
Time Frame: 15 years
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Overall survival is measured from the time the patient goes on treatment until death.
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15 years
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Progression-Free Survival
Time Frame: 15 years
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Progression-free survival associated with 3 part therapy consisting of induction chemotherapy, surgery and risk-adapted use of chemoradiation.
Defined as per RECIST criteria.
Physical examination, imaging of target lesions by CT scan or MRI and chest imaging (CT or Chest x-ray, if clinically indicated) every 3 months (+/- 30 days) for 18 months following end of treatment.
"Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
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15 years
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Voice and Swallowing Function- MD Anderson Dysphagia Inventory (MDADI)
Time Frame: Pre-treatment up to 1 year post surgery
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The MD Anderson Dysphagia Inventory (MDADI) is a 20 item assessment designed to measure voice and swallowing function.
Participants were asked 13 symptom questions and 6 interference items (walking, working) and asked id the 1- strongly agree to 5 strongly disagree.
Scores were summed for a range of 20-100.
The lower the score the worse the outcomes.
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Pre-treatment up to 1 year post surgery
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Voice and Swallowing Function - Voice-Related Quality of Life Assessment (VRQOL)
Time Frame: Pre-treatment up to 1 year post surgery
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The Voice-Related Quality of Life Tool is a 10 item list of possible voice-related problems.
The participant answers 1-5 with 1 being none, not a problem to 5, problem is as bad as it can be.
An algorithm is used to calculate the scores, so that sum scores range from 0 to 100, where 0 indicates poor V-RQOL and 100 indicates good V-RQOL
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Pre-treatment up to 1 year post surgery
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Estimate the Pathologic Complete Response Rate at the Primary Site and in the Neck Following Induction Chemotherapy
Time Frame: 11 weeks
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Pathologic complete response (pCR) is the disappearance of all signs of cancer in tissue samples removed during surgery or biopsy (pT0).
Also called pathologic complete remission.
Pathologic Partial Response (pPR), is the presence of only non-invasive cancer in tissue samples (<pT2)
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11 weeks
|
Response Rates at the Primary Site
Time Frame: 11 weeks
|
Evaluation of target lesions through tumor imaging (CT scan, MRI, and/or chest x-ray) at 3-5 weeks post induction chemotherapy.
Overall response rate will be based on RECIST criteria.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.
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11 weeks
|
Number of Subjects Who Experience Grade 3/4 Adverse Events According to CTCAE 4.0
Time Frame: 18 weeks
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The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting.
A grading (severity) scale is provided for each AE term.
Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL).
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.
Grade 4 Life-threatening consequences; urgent intervention indicated.
Grade 5 Death related to AE.
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18 weeks
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the Kinome Response to Induction Chemotherapy
Time Frame: 11 weeks
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Describe the kinome response to induction chemotherapy (lapatinib, paclitaxel, and carboplatin) in patients who consent to this optional evaluation via co-enrollment in LCCC0121
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11 weeks
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Response Rates at the Neck.
Time Frame: 11 weeks
|
Evaluation of target lesions through tumor imaging (CT scan, MRI, and/or chest x-ray) at 3-5 weeks post induction chemotherapy.
Overall response rate will be based on RECIST criteria.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for neck lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.
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11 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Jared Weiss, MD, University of North Carolina, Chapel Hill
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2012
Primary Completion (Actual)
November 1, 2016
Study Completion (Estimated)
November 1, 2031
Study Registration Dates
First Submitted
May 31, 2012
First Submitted That Met QC Criteria
June 1, 2012
First Posted (Estimated)
June 5, 2012
Study Record Updates
Last Update Posted (Actual)
September 15, 2023
Last Update Submitted That Met QC Criteria
September 13, 2023
Last Verified
April 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Neoplasms, Squamous Cell
- Head and Neck Neoplasms
- Carcinoma
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Protein Kinase Inhibitors
- Carboplatin
- Paclitaxel
- Cisplatin
- Lapatinib
Other Study ID Numbers
- LCCC1125
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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