Clinical trial NCT01711658: TRYHARD: Radiation Therapy Plus Cisplatin With or Without Lapatinib in Treating Patients With Head and Neck Cancer.
Official title: TRYHARD: A Phase II, Randomized, Double Blind, Placebo-Controlled Study of Lapatinib (Tykerb®) for Non-HPV Locally Advanced Head and Neck Cancer With Concurrent Chemoradiation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-HPV Locally Advanced Head and Neck Cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: GlaxoSmithKline
name: Novartis
First posted: 2012-10-22
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: PURPOSE: This trial is studying if and how well lapatinib adds to the effectiveness of radiation therapy plus cisplatin in patients who have head and neck cancer that is not related to the human papillomavirus (HPV).


Eligibility criteria: Inclusion criteria:

* Patients must have histologically or cytologically confirmed diagnosis (from primary lesion and/or lymph nodes) of Squamous Cell Cancer of the oropharynx, hypopharynx or larynx (For patients with oropharynx primary, the tumor must be negative for p16 by immunohistochemistry).
* Patients with selected Stage III or IV disease (T2 N2-3 M0, T3-4 any N M0, T1 N2b, N2c or N3 p16 negative oropharynx cancer or T1-2 any N+ hypopharynx cancer) including no distant metastases.
* History/Physical examination by a Radiation Oncologist and Medical oncologist prior to entering the study.
* Examination by an ears, nose, throat (ENT) or Head \& Neck Surgeon including laryngopharyngoscopy prior to entering the study.
* Patients must have a chest CT scan, or positron emission tomography (PET)/CT scan to rule out metastatic disease
* Patients must have a contrast enhanced CT scan or MRI or PET/CT scan of the tumor site and neck nodes prior to entering the study.
* Patients must have an EKG and echocardiogram (ECHO) or multigated acquisition (MUGA) scan prior to entering the study.
* Patients must have Zubrod Performance Status of 0-1.
* Patients must be ≥ 18 years of age.
* Patients must have normal organ and marrow function as defined below:

  * Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
  * Platelets ≥ 100,000 cells/mm3
  * Hemoglobin ≥ 8.0 g/dl
  * Serum creatinine \< 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min
  * Total bilirubin \< 2 x the institutional upper limit of normal
  * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 x the institutional upper limit of normal
* Patient must have magnesium, calcium, glucose, potassium and sodium levels within normal limits
* Women of childbearing potential must have a negative pregnancy test prior to registration.
* Patients of reproductive potential must practice effective contraception while on study and for at least 60 calendar days following treatment.
* All patients must sign an informed consent prior to enrollment.
* Patients must comply with the treatment plan and follow-up schedule.

Exclusion criteria:

* Patients with simultaneous primaries or bilateral tumors.
* Patients who have had gross total excision of the primary tumor.
* Patients with initial surgical treatment, radical or modified neck dissection.
* Patients who received prior systemic chemotherapy for the study cancer.
* Patients who received prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
* Patients with primary tumor of oral cavity, nasopharynx, sinuses or salivary glands.
* Prior allergic reaction to the study drugs.
* Patients who have had prior therapy that specifically and directly targets the epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) pathway.
* Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment);
* Pregnant women or sexually active patients not willing or able to use medically acceptable forms of contraceptive method while on treatment.
* Patients with severe, active co-morbidity, defined as follows:

  * Uncontrolled cardiac disease, such as uncontrolled hypertension, unstable angina, and/or congestive heart failure requiring hospitalization within the last 6 months
  * Transmural myocardial infarction within the last 6 months
  * Left ventricular ejection fraction \< 45%
  * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  * Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 calendar days prior to registration
  * Hepatic insufficiency resulting in clinical jaundice and/or Coagulation defects
  * Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition

Primary outcomes:
measure: Percentage of Participants Alive Without Progression (Progression-free Survival)
timeFrame: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.
Secondary outcomes:
measure: Percentage of Participants Alive (Overall Survival)
timeFrame: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.
measure: Percentage of Participants With Distant Metastases
timeFrame: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.
measure: Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events
timeFrame: From start of treatment to last follow-up. Maximum follow-up at time of analysis was 7.1 years.
measure: Percentage of Participants Who Complied With Protocol Treatment
timeFrame: From start of treatment to end of treatment (approximately 5 months from randomization).
measure: Percentage of Participants With Local-regional Progression
timeFrame: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.
measure: Performance Status Scale for Head & Neck Cancer.
timeFrame: 3 months, 1 year, and 2 years
measure: Functional Assessment of Cancer Therapy - Head & Neck.
timeFrame: 3 months, 1 year, and 2 years.
measure: University of Michigan Xerostomia-Related Quality of Life Scale.
timeFrame: 3 months, 1 year, and 2 years.
measure: HER2, EGFR, EMT as Biomarkers of Response.
timeFrame: End of Study
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Sacramento
country: United States
facility: Sutter General Hospital
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Louisville
country: United States
facility: James Graham Brown Cancer Center at University of Louisville
state: Kentucky
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Furlong
country: United States
facility: Fox Chase Cancer Center Buckingham
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical School
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
Study officials:
affiliation: Medical College of Wisconsin
name: Stuart Wong, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7.
citation: Harrington K. et al. Phase II study of oral Lapatinib, a dual-tyrosine kinase inhibitor, combined with chemoradiotherapy (CRT) in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). J Clin Oncol. 28:15s, 2010 suppl. Abstract 5505. GSK study 884