Sargramostim, Vaccine Therapy, or Sargramostim and Vaccine Therapy in Preventing Disease Recurrence in Patients With Melanoma That Has Been Removed By Surgery
Condition: Iris Melanoma; Medium/Large Size Posterior Uveal Melanoma; Mucosal Melanoma; Ocular Melanoma With Extraocular Extension; Recurrent Melanoma; Recurrent Uveal Melanoma; Small Size Posterior Uveal Melanoma; Stage IIA Cutaneous Melanoma AJCC v6 and v7; Stage IIA Uveal Melanoma AJCC v7; Stage IIB Cutaneous Melanoma AJCC v6 and v7; Stage IIB Uveal Melanoma AJCC v7; Stage IIC Cutaneous Melanoma AJCC v6 and v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIA Uveal Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIB Uveal Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IIIC Uveal Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Uveal Melanoma AJCC v7
MeSH terms: Melanoma; Skin Neoplasms; Uveal Neoplasms; Recurrence
Intervention: Laboratory Biomarker Analysis; Placebo; Placebo; Sargramostim; Tyrosinase Peptide
Intervention description: Correlative studies; Given GM-CSF placebo SC; Given peptide placebo SC; Given SC; Given SC
Intervention MeSH terms: Sargramostim
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Investigator)
Enrollment: 815.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies sargramostim or vaccine therapy alone to see how well
      they work compared to sargramostim and vaccine therapy together in preventing disease
      recurrence in patients with melanoma that has been removed by surgery. Sargramostim may
      stimulate the immune system in different ways and stop tumor cells from growing. Vaccines
      made from peptides may help the body build an effective immune response to kill tumor cells.
      It is not yet known whether yeast derived sargramostim and vaccine therapy are more effective
      alone or together in preventing recurrence of melanoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have HLA-A2 status known prior to randomization; typing may be obtained
             through a local laboratory facility or through a reference lab utilized by the
             initiating institution; if typing is not available through these means, it may be
             obtained from the University of Pittsburgh

          -  All patients must have disease completely resected with one of the following in order
             to be eligible:

               -  Completely resected disease

               -  Any locoregional recurrence after prior adjuvant interferon or failure on S008

               -  Any local recurrence of disease after adequate surgical excision of the original
                  primary

               -  Mucosal melanoma

               -  Stage IV melanoma (cutaneous, ocular, mucosal, or unknown primary)

          -  The following groups of patients may be entered onto this trial only if they are
             ineligible for S0008 or are, in the opinion of the managing physician, medically unfit
             to receive standard high-dose interferon:

               -  Any clinically evident satellite or in-transit disease

               -  Stage II disease with gross extracapsular extension

               -  Recurrence in a previously resected nodal basin

               -  Four or more involved lymph nodes or matted lymph nodes

               -  Ulcerated primary melanoma and any involved lymph nodes

                    -  NOTE: Patients who are eligible for S0008 will be strongly encouraged to
                       participate in that study in preference to this one

          -  Patients must have been surgically rendered free of disease with negative margins on
             resected specimens; patients rendered free of disease by non-surgical means are not
             eligible

          -  Patients must be randomized within 112 days (16 weeks) of surgical resection; if more
             than one surgical procedure is required to render the patient disease-free, all
             required surgeries must be accomplished within this 16 week time period

          -  Patients must not have received any adjuvant treatment (chemotherapy, biotherapy, or
             limb perfusion) after the resection(s) that make(s) them eligible for this trial; one
             systemic treatment after a prior surgery is allowed, and must have been completed >= 8
             weeks prior to randomization; (when chemotherapy and biotherapy are given together as
             one planned treatment [biochemotherapy], this counts as one regimen); NOTE: Previous
             radiation therapy, including after the resection, is allowed as long as 30 days elapse
             between the radiation and initiation of therapy

          -  Prior treatment with GM-CSF or any peptides used in this protocol, is not allowed

          -  Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  Patients must not have an active infection requiring treatment with parenteral
             antibiotics

          -  Patients must not have other significant medical, surgical, or psychiatric conditions
             or require any medication or treatment that may interfere with compliance on any of
             the E4697 treatment regimens

          -  Patients must not have a diagnosis or evidence of organic brain syndrome or
             significant impairment of basal cognitive function or any psychiatric disorder that
             might preclude participation in the full protocol

          -  Patients must be able to self-administer or arrange for administration of subcutaneous
             injections

          -  Patients who have other current malignancies are not eligible

          -  Patients with prior history at any time of any in situ cancer, lobular carcinoma of
             the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or Clark
             I melanoma in situ are eligible; patients who meet this criteria must be disease-free
             at time of randomization

          -  Patients with prior history of basal or squamous skin cancer are eligible; patients
             who meet this criteria must be disease-free at time of randomization

          -  Patients who have had multiple primary melanomas are eligible

          -  Patients with other malignancies are eligible if they have been continuously disease
             free for > 5 years prior to the time of randomization

          -  Patients must not have autoimmune disorders, conditions of immunosuppression or
             treatment with systemic corticosteroids, including oral steroids (i.e., prednisone,
             dexamethasone), continuous use of topical steroid creams or ointments, or any steroid
             containing inhalers; replacement doses of steroids for patients with adrenal
             insufficiency are allowed; patients who discontinue use of these classes of medication
             for at least 2 weeks prior to randomization are eligible if, in the judgment of the
             treating physician, the patient is not likely to require these classes of drugs during
             the study

          -  Women of childbearing potential must not be pregnant (negative beta human chorionic
             gonadotropin [bHCG] within 2 weeks prior to randomization) or breast-feeding

          -  Women of childbearing potential and sexually active males must be counseled to use an
             accepted and effective method of contraception (including abstinence) while on
             treatment and for a period of 18 months after completing or discontinuing treatment

          -  All patients must have brain computed tomography (CT) or magnetic resonance imaging
             (MRI), chest CT or chest x-ray (CXR), and abdominal (liver) CT or MRI within 4 weeks
             prior to randomization; positron emission tomography (PET) scans are also acceptable
             in place of CT, CXR and/or abdominal MRI if obtained within 4 weeks prior to
             randomization; patients with lesions on the lower extremity must also have pelvic
             imaging within this time period; this is also strongly recommended for patients with
             lesions on the lower trunk; PET scans are acceptable

          -  Patients with resection of visceral disease must have imaging of the affected
             area/organ documenting disease-free status within 2 weeks prior to randomization

          -  White blood cells (WBC) >= 3,000/mm?

          -  Platelet count >= 100,000/mm?

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2
             x institutional upper limit (IUL) of normal

          -  Bilirubin =< 2 x IUL of normal

          -  Serum creatinine =< 1.8 mg/dl

          -  Alkaline phosphatase and lactate dehydrogenase (LDH) must be performed within 4 weeks
             prior to randomization; LDH must be normal; patients with abnormal alkaline
             phosphatase which is =< 1.25 times the institutional upper limit of normal who have a
             negative CT or MRI of the liver and negative bone scan or a negative PET scan are
             eligible

          -  Patients with bone pain must have a bone scan within 4 weeks prior to randomization to
             document the absence of tumor