Multimodality Risk Adapted Tx Including Induction Chemo for SCCHN Amenable to Transoral Surgery

• Sponsor: UNC Lineberger Comprehensive Cancer Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01612351
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 40
• Location: 1
• Arm: 1
• Duration (Months): 233
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer; Squamous Cell Carcinoma of the Head and Neck	Drug: Carboplatin; Drug: Paclitaxel; Drug: Lapatinib; Drug: Cisplatin; Drug: Cisplatin; Radiation: Ipsilateral Radiation; Radiation: Bilateral Radiation; Procedure: Transoral Surgery	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multimodality Risk Adapted Therapy Including Carboplatin/Paclitaxel/Lapatinib as Induction for Squamous Cell Carcinoma of the Head and Neck Amenable to Transoral Surgical Approaches
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Nov 1, 2016
• Anticipated Study Completion Date: Nov 1, 2031

Arms and Interventions

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.

Drug: Carboplatin; Weekly carboplatin given intravenously for 6 weeks during induction chemotherapy.; Other Names: Paraplatin ; Drug: Paclitaxel; Weekly paclitaxel given intravenously prior to carboplatin infusion for 6 weeks during induction chemotherapy.; Other Names: Taxol ; Drug: Lapatinib; 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: Tykerb ; Drug: Cisplatin; 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: Platinol ; Drug: Cisplatin; 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: Platinol ; Radiation: Ipsilateral Radiation; 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: Radiation therapy ; Radiation: Bilateral Radiation; 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: Radiation therapy ; Procedure: Transoral Surgery; Transoral resection by robotic or microscopic approach, which will be at the discretion of the treating surgeon.; Other Names: Surgery

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [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. 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

Secondary Outcome Measures

1. Feasibility of 3 Part Therapy [2 years]

   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.

2. Number of Patients Who Decreased in Risk Level Post Induction Chemotherapy. [11 weeks]

   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.

3. Overall Survival [15 years]

   Overall survival is measured from the time the patient goes on treatment until death.

4. Progression-Free Survival [15 years]

   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

5. Voice and Swallowing Function- MD Anderson Dysphagia Inventory (MDADI) [Pre-treatment up to 1 year post surgery]

   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.

6. Voice and Swallowing Function - Voice-Related Quality of Life Assessment (VRQOL) [Pre-treatment up to 1 year post surgery]

   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

7. Estimate the Pathologic Complete Response Rate at the Primary Site and in the Neck Following Induction Chemotherapy [11 weeks]

   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)

8. Response Rates at the Primary Site [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.

9. Number of Subjects Who Experience Grade 3/4 Adverse Events According to CTCAE 4.0 [18 weeks]

   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.

10. the Kinome Response to Induction Chemotherapy [11 weeks]

    Describe the kinome response to induction chemotherapy (lapatinib, paclitaxel, and carboplatin) in patients who consent to this optional evaluation via co-enrollment in LCCC0121

11. Response Rates at the Neck. [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599

Sponsors and Collaborators

• UNC Lineberger Comprehensive Cancer Center
• GlaxoSmithKline

Investigators

• Principal Investigator: Jared Weiss, MD, University of North Carolina, Chapel Hill

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of North Carolina Lineberger Comprehensive Cancer Center

Publications

None provided.

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01612351
• Other Study ID Numbers: LCCC 1125
• First Posted: Jun 5, 2012
• Last Update Posted: May 20, 2022
• Last Verified: Apr 1, 2022

• Keywords provided by UNC Lineberger Comprehensive Cancer Center: Head and neck cancer; Squamous Cell Carcinoma; Phase II; Transoral Surgery; Induction Chemotherapy; Carboplatin; Paclitaxel; Lapatinib
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Paclitaxel; Cisplatin; Carboplatin; Lapatinib

Study Results

Participant Flow

Arm/Group Title	Induction Chemotherapy Followed by Transoral Surgery
Arm/Group Description	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.
Period Title: Chemotherapy
STARTED	40
COMPLETED	40
NOT COMPLETED	0
Period Title: Chemotherapy
STARTED	39
COMPLETED	39
NOT COMPLETED	0
Period Title: Chemotherapy
STARTED	39
COMPLETED	39
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Induction Chemotherapy Followed by Transoral Surgery
Arm/Group Description	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.
Overall Participants	40
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	57.5
Sex: Female, Male (Count of Participants)
Female	10 25%
Male	30 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.5%
Not Hispanic or Latino	39 97.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 12.5%
White	34 85%
More than one race	0 0%
Unknown or Not Reported	1 2.5%
Region of Enrollment (participants) [Number]
United States	40 100%
Disease Location (Count of Participants)
Supraglottic Larynx	5 12.5%
Oral Cavity	4 10%
Hypopharynx	1 2.5%
Oropharynx	30 75%
Stage of disease (Count of Participants)
T1N1	1 2.5%
T1N2a	4 10%
T1N2b	6 15%
T2N1	4 10%
T2N2a	5 12.5%
T2N2b	12 30%
T2N2c	2 5%
T3N0	3 7.5%
T3N2c	1 2.5%
T4N1	2 5%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	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
Time Frame	11 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Induction Chemotherapy Followed by Transoral Surgery
Arm/Group Description	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.
Measure Participants	40
Count of Participants [Participants]	37 92.5%

2. Secondary Outcome

Title	Feasibility of 3 Part Therapy
Description	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.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

All participants started to receive study treatment.

Arm/Group Title	Induction Chemotherapy Followed by Transoral Surgery
Arm/Group Description	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.
Measure Participants	40
completed	39 97.5%
not-completed	1 2.5%

3. Secondary Outcome

Title	Number of Patients Who Decreased in Risk Level Post Induction Chemotherapy.
Description	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.
Time Frame	11 weeks

Outcome Measure Data

Analysis Population Description

One patient withdrew before surgery.

Arm/Group Title	Induction Chemotherapy Followed by Transoral Surgery
Arm/Group Description	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.
Measure Participants	39
Count of Participants [Participants]	29 72.5%

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival is measured from the time the patient goes on treatment until death.
Time Frame	15 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Progression-Free Survival
Description	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
Time Frame	15 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Voice and Swallowing Function- MD Anderson Dysphagia Inventory (MDADI)
Description	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.
Time Frame	Pre-treatment up to 1 year post surgery

Outcome Measure Data

Analysis Population Description

Subjects were encouraged to complete the assessments but it was left to their discretion. Participants with data available reported.

Arm/Group Title	Pre-treatment	Post-Induction	1 Year Post Surgery
Arm/Group Description	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.	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.	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.
Measure Participants	39	25	26
Mean (Standard Deviation) [units on a scale]	83.90 (14.04)	86.26 (13.24)	81.90 (16.56)

7. Secondary Outcome

Title	Voice and Swallowing Function - Voice-Related Quality of Life Assessment (VRQOL)
Description	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
Time Frame	Pre-treatment up to 1 year post surgery

Outcome Measure Data

Analysis Population Description

Patients were encouraged to complete the assessment but at their discretion. Participants with data available reported.

Arm/Group Title	Pre-treatment	Post-Induction	1 Year Post Surgery
Arm/Group Description	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.	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.	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.
Measure Participants	38	25	23
Mean (Standard Deviation) [units on a scale]	93.42 (13.20)	92.00 (20.12)	91.85 (13.80)

8. Secondary Outcome

Title	Estimate the Pathologic Complete Response Rate at the Primary Site and in the Neck Following Induction Chemotherapy
Description	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)
Time Frame	11 weeks

Outcome Measure Data

Analysis Population Description

All participants received induction chemotherapy and underwent surgery.

Arm/Group Title	Induction Chemotherapy Followed by Transoral Surgery
Arm/Group Description	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.
Measure Participants	39
Pathologic complete response (pCR)	14 35%
Pathologic Partial Response (pPR)	25 62.5%

9. Secondary Outcome

Title	Response Rates at the Primary Site
Description	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.
Time Frame	11 weeks

Outcome Measure Data

Analysis Population Description

All participants received induction chemotherapy and radiological tumor response evaluation was completed.

Arm/Group Title	Non-Randomized Single-Arm
Arm/Group Description	All participants will receive induction chemotherapy and response evaluation was completed.
Measure Participants	39
Complete Response	15 37.5%
Partial Response	21 52.5%
Stable Disease	3 7.5%

10. Secondary Outcome

Title	Number of Subjects Who Experience Grade 3/4 Adverse Events According to CTCAE 4.0
Description	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.
Time Frame	18 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Induction Chemotherapy Followed by Transoral Surgery
Arm/Group Description	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.
Measure Participants	40
Alanine aminotransferase increased	2 5%
Aspartate Aminotransferase increased	1 2.5%
Chest pain- cardiac	1 2.5%
Diarrhea	5 12.5%
Fatigue	4 10%
Febrile neutropenia	4 10%
Hyperglycemia	1 2.5%
Hyponatremia	1 2.5%
Hypotension	1 2.5%
Lymphocyte count decreased	1 2.5%
Nausea	1 2.5%
Neutrophil count decreased	22 55%
Palmar-plantar erythrodysesthesia syndrome	1 2.5%
Peripheral sensory neuropathy	2 5%
Rash acneiform	4 10%
Sepsis	1 2.5%
White blood cell decreased	15 37.5%

11. Secondary Outcome

Title	the Kinome Response to Induction Chemotherapy
Description	Describe the kinome response to induction chemotherapy (lapatinib, paclitaxel, and carboplatin) in patients who consent to this optional evaluation via co-enrollment in LCCC0121
Time Frame	11 weeks

Outcome Measure Data

Analysis Population Description

The data were unable to be analyzed because co-enrollment with LCCC0121 could not be implemented.

Arm/Group Title	Induction Chemotherapy Followed by Transoral Surgery
Arm/Group Description	All participants received LCCC1125 study treatment and co-enrolled with o-enrollment with the LCCC0121 study.
Measure Participants	0

12. Secondary Outcome

Title	Response Rates at the Neck.
Description	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.
Time Frame	11 weeks

Outcome Measure Data

Analysis Population Description

All participants received induction chemotherapy and radiological tumor response evaluation was completed.

Arm/Group Title	Non-Randomized Single-Arm
Arm/Group Description	All participants will receive induction chemotherapy and response evaluation was completed.
Measure Participants	29
Complete Response	11 27.5%
Partial Response	15 37.5%
Stable Disease	3 7.5%

Adverse Events

Time Frame	13 weeks
Arm/Group Title	Induction Chemotherapy Followed by Transoral Surgery
Arm/Group Description	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.
All Cause Mortality
	Induction Chemotherapy Followed by Transoral Surgery
	Affected / at Risk (%)	# Events
Total	0/40 (0%)
Serious Adverse Events
	Induction Chemotherapy Followed by Transoral Surgery
	Affected / at Risk (%)	# Events
Total	7/40 (17.5%)
Blood and lymphatic system disorders
Febrile neutropenia	2/40 (5%)
Cardiac disorders
Chest pain - cardiac	1/40 (2.5%)
Gastrointestinal disorders
Diarrhea	2/40 (5%)
Ileus	1/40 (2.5%)
Nausea	1/40 (2.5%)
Vomiting	1/40 (2.5%)
Investigations
Neutrophil count decreased	2/40 (5%)
White blood cell decreased	1/40 (2.5%)
Metabolism and nutrition disorders
Dehydration	1/40 (2.5%)
Hyponatremia	1/40 (2.5%)
Nervous system disorders
Peripheral sensory neuropathy	1/40 (2.5%)
Psychiatric disorders
Confusion	1/40 (2.5%)
Other (Not Including Serious) Adverse Events
	Induction Chemotherapy Followed by Transoral Surgery
	Affected / at Risk (%)	# Events
Total	39/40 (97.5%)
Blood and lymphatic system disorders
Anemia	25/40 (62.5%)
Febrile neutropenia	2/40 (5%)
Eye disorders
Blurred vision	2/40 (5%)
Gastrointestinal disorders
Abdominal pain	5/40 (12.5%)
Constipation	12/40 (30%)
Diarrhea	28/40 (70%)
Dry mouth	2/40 (5%)
Mucositis oral	4/40 (10%)
Nausea	22/40 (55%)
Oral pain	2/40 (5%)
Vomiting	5/40 (12.5%)
General disorders
Dyspepsia	3/40 (7.5%)
Edema face	2/40 (5%)
Edema limbs	4/40 (10%)
Fatigue	20/40 (50%)
Fever	2/40 (5%)
Pain	5/40 (12.5%)
Investigations
Alanine aminotransferase increased	12/40 (30%)
Aspartate aminotransferase increased	13/40 (32.5%)
Blood bilirubin increased	6/40 (15%)
Creatinine increased	4/40 (10%)
Lymphocyte count decreased	10/40 (25%)
Neutrophil count decreased	31/40 (77.5%)
Platelet count decreased	6/40 (15%)
White blood cell decreased	33/40 (82.5%)
Metabolism and nutrition disorders
Anorexia	5/40 (12.5%)
Dehydration	5/40 (12.5%)
Hyperglycemia	2/40 (5%)
Hypoalbuminemia	8/40 (20%)
Hypocalcemia	5/40 (12.5%)
Hypokalemia	8/40 (20%)
Hypomagnesemia	9/40 (22.5%)
Hyponatremia	8/40 (20%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/40 (7.5%)
Bone pain	2/40 (5%)
Flank pain	2/40 (5%)
Myalgia	10/40 (25%)
Pain in extremity	3/40 (7.5%)
Nervous system disorders
Dysgeusia	10/40 (25%)
Headache	2/40 (5%)
Peripheral sensory neuropathy	14/40 (35%)
Psychiatric disorders
Anxiety	2/40 (5%)
Insomnia	4/40 (10%)
Renal and urinary disorders
Urinary tract pain	2/40 (5%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	4/40 (10%)
Sore throat	2/40 (5%)
Skin and subcutaneous tissue disorders
Alopecia	12/40 (30%)
Dry skin	3/40 (7.5%)
Palmar-plantar erythrodysesthesia syndrome	3/40 (7.5%)
Rash acneiform	18/40 (45%)
Rash maculo-papular	2/40 (5%)
Vascular disorders
Hypotension	3/40 (7.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.