RTOG 3501 TRYHARD: A PHASE II, RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED STUDY OF LAPATINIB (TYKERB(RegisteredTM)) FOR NON-HPV LOCALLY ADVANCED HEAD AND NECK CANCER WITH CONCURRENT CHEMORADIATION

Study ID
STU 062012-078

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

Contact
Susan Cooley
214-633-1754
susan.cooley@utsouthwestern.edu

Principal Investigator
John Yordy

Summary

We hypothesize that, due to the disruptive effect of lapatinib upon eGFR and HeR2 signaling
pathways, the addition of concurrent and maintenance lapatinib to a concurrent radiationcisplatin regimen will enhance the cytotoxic effect, resulting in an improvement of PFS in highrisk (non-HPV) La-HnSCC patients.

Treatment arms
Week 1: lapatinib or placebo only
Weeks 2-8: lapatinib or placebo and Radiation Therapy
on Days 8 and 29: Cisplatin
Followed by lapatinib or placebo for 3 months

Participant Eligibility

1. Pathologically (histologically or cytologically) proven diagnosis (from primary lesion and/or
lymph nodes) diagnosis of squamous cell carcinoma of the oropharynx, hypopharynx, or larynx;

2. For patients with an oropharynx primary, the tumor must be negative for p16 by
immunohistochemistry;

3. 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, based upon the following minimum diagnostic workup:
*History/physical examination within 28 calendar days prior to registration, including an
examination by a Medical Oncologist and Radiation Oncologist and documentation of the
patient[Single Quote]s weight;
*Examination by an ENT or Head & Neck Surgeon, including laryngopharyngoscopy (mirror
and/or fiberoptic and/or direct procedure) within 42 days prior to registration;
*Chest CT scan, or PET/CT scan within 42 calendar days prior to registration to rule out
metastatic disease;
*CT scan, MRI, or PET/CT scan of the tumor site and neck nodes within 42 calendar days
prior to registration;
*EKG and ECHO or MUGA scan within 84 calendar days prior to registration;

4. Zubrod Performance Status 0-1 within 14 calendar days prior to registration;

5. Age >= 18;

6.CBC/differential obtained within 14 calendar days prior to registration, with adequate bone
marrow function defined as follows:
*Absolute neutrophil count (ANC) >= 1,500 cells/mm3;
*Platelets >= 100,000 cells/mm3;
*Hemoglobin >= 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb >=
8.0 g/dl is acceptable.);

7. Adequate renal and hepatic function within 14 calendar days prior to registration, defined as
follows:
*Serum creatinine < 1.5 mg/dl or creatinine clearance (CC) >= 50 ml/min within 14 calendar
days prior to registration, determined by 24-hour collection or estimated by Cockcroft-Gault
formula
*Total bilirubin < 2 x the institutional ULN;
*AST or ALT <= 3 x the institutional ULN;

8. Magnesium, calcium, glucose, potassium, and sodium within 14 calendar days prior to
registration, with the following required parameters:
*Magnesium: > 0.9 mg/dl or < 3 mg/dl;
*Calcium: > 7 mg/dl or < 12.5 mg/dl;
*Glucose: > 40 mg/dl or < 250 mg/dl;
*Potassium: > 3 mmol/L or < 6 mmol/L;
*Sodium: > 130 mmol/L or < 155 mmol/L.

9. Negative serum pregnancy test within 14 calendar days prior to registration for women of
childbearing potential;

10. Women of childbearing potential and men who are sexually active must practice adequate
contraception during treatment and for at least 60 calendar days following treatment.

11. Patients must be deemed able to comply with the treatment plan and follow-up schedule.

12. Patients must provide study specific informed consent prior to study entry, including, for
oropharyngeal cancer patients, consent for mandatory submission of tissue for required, central
p16 review.