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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by UNC Lineberger Comprehensive Cancer Center
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01612351
First received: May 31, 2012
Last updated: February 15, 2013
Last verified: February 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Overall Response Rate [ Time Frame: 11 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Feasibility of 3 part therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.

  • Post Induction Chemotherapy Changes in Risk Level [ Time Frame: 11 weeks ] [ Designated as safety issue: No ]
    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.

  • Progression Free Survival and Overall Survival [ Time Frame: 15 years ] [ Designated as safety issue: No ]
    Will be 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.

  • Voice and Swallowing Function [ Time Frame: 11 weeks ] [ Designated as safety issue: No ]
    Assessed by Functional Outcome Swallowing Scale (FOSS) scores, the MD Anderson Dysphagia Inventory (MDADI), the dysphagia-specific quality of life tool (SWAL-QOL), and voice related quality of life tool (V-RQOL), and through videolaryngoscopy evaluation of the aerodigestive tract at screening and 3-5 weeks post induction chemotherapy.

  • Number of subjects who experience adverse events [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
    Toxicity will be graded using CTCAE criteria.


Estimated Enrollment: 40
Study Start Date: June 2012
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low Risk
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.
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
Procedure: Transoral Surgery
Transoral resection by robotic or microscopic approach, which will be at the discretion of the treating surgeon.
Other Name: Surgery
Experimental: Medium Risk
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 medium risk category will receive ipsilateral radiation concurrent with weekly cisplatin.
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
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
Procedure: Transoral Surgery
Transoral resection by robotic or microscopic approach, which will be at the discretion of the treating surgeon.
Other Name: Surgery
Experimental: High Risk
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 high risk category will receive bilateral radiation concurrent with cisplatin every 3 weeks plus daily lapatinib.
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
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: 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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 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 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:

  • T1N0 disease or 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01612351

Contacts
Contact: Dale Flowers, RN, OCN 919-966-4432 dale_flowers@med.unc.edu

Locations
United States, North Carolina
The University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Dale Flowers, RN, OCN    919-966-4432    dale_flowers@med.unc.edu   
Principal Investigator: Jared Weiss, MD         
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:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01612351     History of Changes
Other Study ID Numbers: LCCC 1125
Study First Received: May 31, 2012
Last Updated: February 15, 2013
Health Authority: United States: Institutional Review Board

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
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Lapatinib
Cisplatin
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 28, 2014