Trial Using Gilotrif for Advanced Penile Squamous Cell Carcinoma
Condition: Penile Squamous Cell Carcinoma (PSCC)
MeSH terms: Carcinoma; Carcinoma, Squamous Cell
Intervention: Gilotrif
Intervention description: Patients will take a single oral dose of Gilotrif each day starting at 40 mg. Dose escalation and reductions can occur.
Intervention MeSH terms: Afatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Epidermal growth factor receptor (EGFR),; Human Papillomavirus (HPV); Penile squamous cell carcinoma (PSCC); Gilotrif

Summary:

      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.
    

Eligibility criteria:

        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.