Sargramostim, Vaccine Therapy, or Sargramostim and Vaccine Therapy in Preventing Disease Recurrence in Patients With Melanoma That Has Been Removed By Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01989572
First received: November 18, 2013
Last updated: NA
Last verified: November 2013
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Ciliary Body and Choroid Melanoma, Medium/Large Size
Ciliary Body and Choroid Melanoma, Small Size
Extraocular Extension Melanoma
Iris Melanoma
Metastatic Intraocular Melanoma
Mucosal Melanoma
Recurrent Intraocular Melanoma
Recurrent Melanoma
Stage IIA Intraocular Melanoma
Stage IIA Melanoma
Stage IIB Intraocular Melanoma
Stage IIB Melanoma
Stage IIC Melanoma
Stage IIIA Intraocular Melanoma
Stage IIIA Melanoma
Stage IIIB Intraocular Melanoma
Stage IIIB Melanoma
Stage IIIC Intraocular Melanoma
Stage IIIC Melanoma
Stage IV Intraocular Melanoma
Stage IV Melanoma
Biological: sargramostim
Biological: tyrosinase peptide
Other: placebo
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Randomized, Placebo-Controlled Phase III Trial of Yeast Derived GM-CSF Versus Peptide Vaccination Versus GM-CSF Plus Peptide Vaccination Versus Placebo in Patients With "No Evidence of Disease" After Complete Surgical Resection of "Locally Advanced" and/or Stage IV Melanoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
    Performed using a two-sided log-rank test stratified on HLA-A2 status, site of metastases, and number of metastatic lesions, using an overall type I error of 0.05. Overall survival of PEP+ vs PEP- groups in the HLA-A2+ population will be compared.


Secondary Outcome Measures:
  • Disease-free survival [ Time Frame: From randomization to date of recurrence or death, whichever comes first, assessed up to 15 years ] [ Designated as safety issue: No ]
    The cure rate model will be used to compare the peptide positive versus the peptide negative groups. The truncated O'Brien-Fleming boundaries will be used for the interim analyses with an overall two-sided type I error rate of 0.05. The stratified log-rank test, stratifying on the presence and absence of sargramostim, will be used in this comparison.


Other Outcome Measures:
  • Change in number of T-cells [ Time Frame: Baseline up to day 43 ] [ Designated as safety issue: No ]
    The statistical analysis for this endpoint will involve doing a two-sample Wilcoxon rank sum test for the null hypothesis that d equals zero against the alternative that d does not equal zero.

  • Change in number of circulating dendritic cells [ Time Frame: Baseline up to day 43 ] [ Designated as safety issue: No ]
    The statistical analysis for this endpoint will involve doing a two-sample Wilcoxon rank sum test for the null hypothesis that d equals zero against the alternative that d does not equal zero.

  • Immune response in terms of cluster of differentiation (CD)8 T-cells and CD4 T-cell responses [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    The raw ELISPOT counts will be used in a repeated measures analysis to estimate changes in the mean counts as a function of treatment group


Enrollment: 800
Study Start Date: February 2000
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (sargramostim, peptide vaccine)
Patients receive sargramostim SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses).
Biological: sargramostim
Given SC
Other Names:
  • GM-CSF
  • Leukine
  • Prokine
Biological: tyrosinase peptide
Given SC
Other Name: TYRP
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (sargramostim placebo, peptide vaccine)
Patients receive sargramostim placebo SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses).
Biological: tyrosinase peptide
Given SC
Other Name: TYRP
Other: placebo
Given GM-CSF placebo SC
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm III (sargramostim, peptide placebo)
Patients receive sargramostim SC on days 1-14 and peptide placebo mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses).
Biological: sargramostim
Given SC
Other Names:
  • GM-CSF
  • Leukine
  • Prokine
Other: placebo
Given peptide placebo SC
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies
Placebo Comparator: Arm IV (placebo, peptide placebo)
Patients receive placebo SC on days 1-14 and peptide placebo on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses).
Other: placebo
Given GM-CSF placebo SC
Other Name: PLCB
Other: placebo
Given peptide placebo SC
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm V (sargramostim)
Patients receive sargramostim SC on days 1-14.
Biological: sargramostim
Given SC
Other Names:
  • GM-CSF
  • Leukine
  • Prokine
Other: laboratory biomarker analysis
Correlative studies
Placebo Comparator: Arm VI (sargramostim placebo)
Patients receive sargramostim placebo SC on days 1-14.
Other: placebo
Given GM-CSF placebo SC
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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/mm³
  • Platelet count >= 100,000/mm³
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01989572

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Investigators
Principal Investigator: David Lawson Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01989572     History of Changes
Obsolete Identifiers: NCT00005034
Other Study ID Numbers: NCI-2013-02101, NCI-2013-02101, CALGB 500101, U10CA021115, ECOG-4697, CDR0000067568, SWOG-E4697, E4697, E4697, U10CA021115
Study First Received: November 18, 2013
Last Updated: November 18, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases

ClinicalTrials.gov processed this record on August 01, 2014