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

• ClinicalTrials.gov Identifier: NCT01612351
• Recruitment Status: Active, not recruiting
• First Posted: June 5, 2012
• Results First Posted: October 13, 2017
• Last Update Posted: December 8, 2021
• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): UNC Lineberger Comprehensive Cancer Center

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; 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 (Clinical Trial)
• 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: June 2012
• Actual Primary Completion Date: November 2016
• Estimated Study Completion Date: November 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 Name: Paraplatin; Drug: Paclitaxel; Weekly paclitaxel given intravenously prior to carboplatin infusion for 6 weeks during induction chemotherapy.; Other Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Radiation therapy; Procedure: Transoral Surgery; Transoral resection by robotic or microscopic approach, which will be at the discretion of the treating surgeon.; Other Name: Surgery

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate [ 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. 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 [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 15 years ]
   Overall survival is measured from the time the patient goes on treatment until death.
4. Progression-Free Survival [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ 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.
8. Response Rates at Both the Primary Site and in 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 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 [ Time Frame: 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. 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 ]

Eligibility Criteria

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

Criteria

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

United States, North Carolina

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

More Information

Additional Information:

University of North Carolina Lineberger Comprehensive Cancer Center 

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01612351
• Other Study ID Numbers: LCCC 1125
• First Posted: June 5, 2012
• Results First Posted: October 13, 2017
• Last Update Posted: December 8, 2021
• Last Verified: December 2021

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; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Neoplasms by Site; Paclitaxel; Cisplatin; Carboplatin; Lapatinib; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Protein Kinase Inhibitors; Enzyme Inhibitors