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

UNC Lineberger Comprehensive Cancer Center40 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Head and Neck Cancer Squamous Cell Carcinoma of the Head and Neck

Interventions

CarboplatinDRUG

Weekly carboplatin given intravenously for 6 weeks during induction chemotherapy.

PaclitaxelDRUG

Weekly paclitaxel given intravenously prior to carboplatin infusion for 6 weeks during induction chemotherapy.

LapatinibDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Outcomes

Primary Outcomes

Overall Response Rate

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

Secondary Outcomes

Feasibility of 3 Part Therapy

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

Number of Patients Who Decreased in Risk Level Post Induction Chemotherapy.

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

Overall Survival

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

Time frame: up to 7.25 years

Progression-Free Survival

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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.