Pilot hu14.18-IL2 in Resectable Recurrent Stage III or Stage IV Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: hu14.18-IL2; hu14.18-IL2
Intervention description: 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2; Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course
Intervention MeSH terms: Interleukin-2
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 15 Years
Healthy volunteers: No
Keywords: Melanoma; hu14.18-IL2

Summary:

      Evaluate the antitumor activity of hu14.18-IL2 in the minimal residual disease setting.
      Evaluate the time to recurrence and overall survival of patients treated with hu14.18-IL2.
    

Eligibility criteria:

        Inclusion criteria

          1. Subjects must have recurrent stage III (i.e., recurrent regional metastasis), or stage
             IV (i.e., any distant metastasis) melanoma for which surgical resection would be
             clinically recommended, with biopsy proven (current or previous) Stage III or Stage IV
             disease. Any biopsies obtained to demonstrate recurrent regional metastasis or distant
             metastasis must be considered clinically appropriate for clinical management and must
             not be performed solely for meeting eligibility criteria. In addition, subjects must
             have disease that has not yet been completely excised.

          2. Patients must have disease which involves 3 or fewer sites. A nodal basin recurrence
             will be scored as one site, even if multiple nodes are positive. "Clustered"
             subcutaneous and/or cutaneous lesions that can be removed in a single surgical
             excision will be scored as one site, even if multiple subcutaneous and/or cutaneous
             lesions are present.

          3. The subjects' disease is determined to be completely resectable with uninvolved
             margins using standard surgical guidelines based on physical exam and radiographic
             imaging (MRI or CT of the head, and CT or MRI of the chest, abdomen and pelvis).

          4. Subjects must have one of the following: a) Stage III melanoma with recurrence after
             prior surgery, with or without subsequent adjuvant systemic (standard or experimental)
             and/or radiotherapy management Or b) Stage IV melanoma (cutaneous, ocular, mucosal, or
             unknown primary)

          5. Subjects must be 18 years old or older OR if they are 15 years old or greater,
             considered to be mature minors, able to give adult informed consent (with parental
             co-signature), meet all other eligibility criteria, and also weigh at least 45 kg..
             Subjects must weigh at least 45 kg in order to safely provide sufficient blood for
             monitoring studies (see section 7.7 for details).

          6. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0 or 1.

          7. Subjects must have adequate bone marrow, liver, and renal function.

          8. Subjects with one or more of the following cardiac risk factors must complete a stress
             radionuclide scan with no evidence of myocardial ischemia or heart failure: (a) a
             history of cardiac disease, (b) age greater than 65 years old, (c) any clinically
             significant abnormality found on ECG (required at baseline), or (d) significant risk
             factors for coronary artery disease (history of significant dyslipidemia; any
             treatment for dyslipidemia; or two first degree relatives with a documented myocardial
             infarction prior to age 55).

          9. Subjects with significant history of pulmonary disease, shortness of breath at rest,
             or known Chronic Obstructive Pulmonary Disease (COPD) must have pulmonary function
             tests within 35% of normal age-predicted values.

         10. Subjects must be willing and able to provide informed written consent prior to any
             study-related procedures.

         11. Subjects must have no immediate requirements for palliative chemotherapy, palliative
             radiotherapy, or palliative hormonal therapy.

         12. Subjects must be willing and able to discontinue antihypertensive medications if
             advised to do so for days of hu14.18-IL2 infusion.

         13. Subjects must have slides available from stage III or stage IV melanoma. Paraffin
             blocks are preferable, but at a minimum, slides documenting melanoma by biopsy
             (including fine needle cytology) must be available for pathology review, and potential
             restaining/staining (see Section 7.4, Surgical Pathology Guidelines). Prior histologic
             demonstration of metastatic melanoma (either stage III or Stage IV) may be utilized if
             a repeat biopsy is not clinically needed to to establish eligibility.

        Exclusion criteria

          1. Subjects are ineligible if they have received monoclonal antibodies (mAb) during
             biologic therapy, tumor imaging, purging of autologous marrow/stem cells for
             re-infusion or for any other reason unless serological testing is performed. If the
             absence of detectable antibody (over background) to hu14.18 is documented, the subject
             is eligible for the study.

          2. Subjects treated with IL2 in the past that developed intolerable (Grade 4) IL2-related
             side effects are not eligible.

          3. Subjects who have received any (standard or experimental) systemic therapy for stage
             IV disease are not eligible.

          4. Women of childbearing potential will be excluded if they are pregnant, nursing, or not
             using effective contraception during the treatment period.

          5. Subjects with symptoms of ischemic cardiac disease, congestive heart failure,
             myocardial infarct within the immediate preceding 6 months and/or uncontrolled cardiac
             rhythm disturbance are ineligible.

          6. Subjects with significant psychiatric disabilities or seizure disorders are
             ineligible.

          7. Subjects who have had major surgery within the past 3 weeks are ineligible.

          8. Subjects with clinically detectable pleural effusions or ascites are ineligible.

          9. Subjects with organ allografts are ineligible.

         10. Subjects who require or are likely to require corticosteroid or other
             immunosuppressive drugs or have used them within 2 weeks of registration are
             ineligible.

         11. Subjects with significant intercurrent illnesses are ineligible.

         12. Subjects with active infections or active peptic ulcer unless these conditions are
             corrected or controlled are ineligible.

         13. Subjects with brain metastases, whether active or inactive, are ineligible. A head MRI
             or head CT scan will be required at baseline to rule out silent metastases.

         14. Subjects with active second malignancy other than non-melanoma skin cancer are
             ineligible. Patients will be considered eligible if they have been continuously
             disease free for > 5 years prior to the time of enrollment.

         15. Subjects who are infected with human immunodeficiency virus (HIV), hepatitis B surface
             antigen (HBs Ag) carrier state or with clinical evidence of hepatitis are ineligible.
             Treatment may be initiated before laboratory confirmation of HIV and HBs Ag
             negativity, but will be stopped if results are positive.

         16. Subjects with a clinically significant neurologic deficit or objective peripheral
             neuropathy (Grade > 2) are ineligible.

         17. Subjects with a known hypersensitivity to the study drug, Tween-80® or to human
             immunoglobulin are ineligible.

         18. Patients with a known history of diabetes mellitus that has required systemic therapy
             within the past 3 months (either oral hypoglycemic agents or insulin) will be
             excluded, as treatment with hu14.18-IL2 may alter blood glucose levels.

         19. Subjects with a legal incapacity or limited legal capacity are ineligible.

         20. Subjects with bone metastases are ineligible.