Trial Using Gilotrif for Advanced Penile Squamous Cell Carcinoma

This is a non-randomized trial phase 2 trial in which the drug Gilotrif will be administered
at an oral dosage of 40 mg daily. This will continue until there is disease progression or
severe toxicities. Patients will undergo a clinical exam every 4 weeks as well as have blood
collected. Radiographic scans will be done every 8 weeks.

Inclusion Criteria:

1. Histologically or cytologically confirmed PSCC.

2. Patients with metastatic or locally advanced unresectable PSCC.

3. Progressive disease after ≥1 prior chemotherapy regimens.

4. Measurable disease by RECIST 1.1 criteria.

5. Prior regimen within 6 months

6. ECOG performance status 0-2.

7. Adequate organ function, defined as all of the following:

- Absolute neutrophil count (ANC) >1500 /mm3. Platelet count >100,000/ mm3.

- Estimated creatinine clearance ≥ 45ml/min.

- Total Bilirubin <1.5 times upper limit of institutional normal; Aspartate amino
transferase (AST) or alanine amino transferase (ALT) <2.5 times the upper limit
of institutional normal (ULN).

- Hemoglobin ≥8.5 g/dl.

8. Resolution of all acute toxic effects of prior chemotherapy or surgical procedures to
NCI CTCAE version 4.03 grade <1, in the opinion of the Treating Physician.

9. Ability to understand and willingness to sign a written informed consent. Age ≥18
years or age of majority at the participating site, whichever is greater.

10. Availability of 20 archival formalin-fixed paraffin embedded tumor tissue slides.

Exclusion Criteria:

1. Patients will have recovered from toxicities from prior systemic anticancer treatment
or local therapies.

2. Prior EGFR inhibitors.

3. Major surgery within 4 weeks or minor surgery within 2 weeks before registration or
scheduled for surgery during the projected course of the study. Wounds will be
completely healed prior to study entry and patients recovered from all toxicities from
surgery. Placement of vascular access device is not considered major or minor surgery
in this regard.

4. Prior radiation therapy is allowed as long as the irradiated area was not the sole
source of measurable disease and radiotherapy was completed with recovery from
toxicity, at least 3 weeks prior to enrollment. If the irradiated area is the only
site of disease, there will be progressive disease.

5. History or presence of clinically relevant cardiovascular abnormalities such as
uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA)
classification of 3, unstable angina or poorly controlled arrhythmia as determined by
the investigator. Myocardial infarction within 6 months prior to registration.

6. Any history of or concomitant condition that, in the opinion of the Investigator,
would compromise the patient's ability to comply with the study or interfere with the
evaluation of the efficacy and safety of the test drug.

7. Previous or concomitant malignancies at other sites, except effectively treated
non-melanoma skin cancers, ductal carcinoma in situ or effectively treated malignancy
that has been in remission for more than 3 years and is considered to be cured.

8. Requiring treatment with any of the prohibited concomitant medications listed in the
protocol that cannot be stopped for the duration of trial participation.

9. Known pre-existing interstitial lung disease.

10. Any history or presence of poorly controlled gastrointestinal disorders that could
affect the absorption of the study drug (e.g. Crohn's disease, ulcerative colitis,
chronic diarrhea, malabsorption).

11. Active hepatitis B infection (defined as presence of Hep BsAg and/ or Hep B DNA),
active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV
carrier.

12. Meningeal carcinomatosis.

13. Patients with active brain or subdural metastases are not eligible, unless they have
completed local (radiation) therapy and have discontinued the use of corticosteroids
or have been on stable dose of corticosteroids for at least 4 weeks before starting
study treatment. Any symptoms attributed to brain metastases will be stable for at
least 4 weeks before starting study treatment.

14. Any active or uncontrolled infection.