Clinical trial NCT01612351: Multimodality Risk Adapted Tx Including Induction Chemo for SCCHN Amenable to Transoral Surgery
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Squamous Cell Carcinoma of the Head and Neck
Keywords: Head and neck cancer
Squamous Cell Carcinoma
Phase II
Transoral Surgery
Induction Chemotherapy
Carboplatin
Paclitaxel
Lapatinib
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2012-06-05
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Eligibility 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

Primary outcomes:
measure: Overall Response Rate
timeFrame: 11 weeks
Secondary outcomes:
measure: Feasibility of 3 Part Therapy
timeFrame: 2 years
measure: Number of Patients Who Decreased in Risk Level Post Induction Chemotherapy.
timeFrame: 11 weeks
measure: Overall Survival
timeFrame: 15 years
measure: Progression-Free Survival
timeFrame: 15 years
measure: Voice and Swallowing Function- MD Anderson Dysphagia Inventory (MDADI)
timeFrame: Pre-treatment up to 1 year post surgery
measure: Voice and Swallowing Function - Voice-Related Quality of Life Assessment (VRQOL)
timeFrame: Pre-treatment up to 1 year post surgery
measure: Estimate the Pathologic Complete Response Rate at the Primary Site and in the Neck Following Induction Chemotherapy
timeFrame: 11 weeks
measure: Response Rates at the Primary Site
timeFrame: 11 weeks
measure: Number of Subjects Who Experience Grade 3/4 Adverse Events According to CTCAE 4.0
timeFrame: 18 weeks
measure: the Kinome Response to Induction Chemotherapy
timeFrame: 11 weeks
measure: Response Rates at the Neck.
timeFrame: 11 weeks
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Jared Weiss, MD
role: PRINCIPAL_INVESTIGATOR
References: