Trial Using Gilotrif for Advanced Penile Squamous Cell Carcinoma

A Phase 2 Trial Using Gilotrif for Advanced Penile Squamous Cell Carcinoma Following Systemic Therapy

Penile squamous cell carcinoma (PSCC) is a highly aggressive and relatively rare disease. Supportive evidence for the value of systemic therapy does not exist for this disease and there are no agents currently approved by regulatory agencies. This study will evaluate the drug Gilotrif in patients with metastatic progressive PSCC following chemotherapy. Gilotrif has shown supportive evidence in non-small cell lung cancer by inhibiting certain proteins that are also found in PSCC. The drug has the potential for some patients to exhibit a response contributing to a greater quality of life.

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.