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Phase III Randomized Study of Sargramostim (GM-CSF) and Peptide Vaccination Comprising Tyrosinase:368-376, gp100:209-217 (210M) Antigen, and MART-1:27-35 Peptide Versus Peptide Vaccination Alone Versus GM-CSF Alone Versus Placebo in Patients With Locally Advanced or Metastatic Melanoma
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outcomes Outline Published Results Trial Contact Information Related Information Registry Information
Alternate Title
Vaccine Therapy and/or Sargramostim in Treating Patients With Locally Advanced or Metastatic Melanoma
Basic Trial Information
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Protocol IDs
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Phase III
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Treatment
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Closed
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18 and over
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NCI
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ECOG-4697 SWOG-E4697, E4697, NCT00005034
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Objectives - Compare overall survival and disease-free survival in HLA-A2-positive or negative patients with completely resected locally advanced or metastatic melanoma treated with or without sargramostim (GM-CSF).
- Compare overall survival and disease-free survival in HLA-A2-positive patients treated with peptide vaccination comprised of tyrosinase:368-376, gp100:209-217 (210M) antigen, and MART-1:27-35 peptide vs no peptide vaccination.
- Compare the influence of GM-CSF on circulating dendritic cell numbers and subpopulations in peripheral blood of patients treated with or without GM-CSF.
- Determine whether immunization with peptides with or without GM-CSF elicits a measurable T-cell response in HLA-A2-positive patients.
Entry Criteria Disease Characteristics:
- Histologically proven completely resected melanoma including one of the
following:
- Any locoregional recurrence after prior adjuvant
interferon or failure on SWOG-0008
- Any local recurrence after adequate surgical excision
of the original primary
- Mucosal melanoma
- Stage IV disease including:
- Cutaneous melanoma
- Ocular melanoma
- Mucosal melanoma
- Multiple primary lesions allowed
- If ineligible for SWOG-0008 or are determined by managing physician to be
medically unfit to receive standard high-dose interferon, patients with
one of the
following may be eligible:
- Any clinically evident satellite or intransit disease
- Stage III disease with gross extracapsular extension
- Recurrence in previously resected nodal basin
- Four or more involved lymph nodes or matted lymph nodes
- Ulcerated primary melanoma and any involved lymph nodes
- Known HLA-A2 status
- Rendered free of disease with negative margins by surgical means only
- Ineligible if rendered free of disease by nonsurgical
means
- Must be randomized within 16 weeks of surgical resection
- If more than one surgical procedure is required to
render the patient disease free, all required surgeries must be completed
within this 16-week time
period
- Patients with bone pain must have a negative bone scan
Prior/Concurrent Therapy:
Biologic therapy: - See Disease Characteristics
- No prior sargramostim (GM-CSF)
- No prior MART-1:27-35 peptide, tyrosinase:368-376, or
gp100:209-217 (210M) antigen
- No prior adjuvant biologic therapy after resection(s) that
rendered the patient disease-free with negative margins
- One prior systemic regimen after prior surgery allowed if
completed at least 8 weeks ago
- Chemotherapy and biologic therapy administered together as
one planned treatment count as one regimen
Chemotherapy: - See Biologic therapy
- No prior adjuvant chemotherapy after resection(s) that
rendered the patient disease-free with negative margins
Endocrine therapy: - At least 2 weeks since prior systemic corticosteroids,
including oral steroids (e.g., prednisone or dexamethasone)
- At least 2 weeks since prior continuous use of topical steroid
creams or ointments or any steroid-containing inhalers
- Concurrent replacement doses of steroids for adrenal
insufficiency allowed
- No concurrent systemic corticosteroids, including oral
steroids (e.g., prednisone or dexamethasone)
- No concurrent continuous use of topical steroid creams or
ointments or any steroid-containing inhalers
Radiotherapy: - At least 30 days since prior radiotherapy, including after the
resection
Surgery: - See Disease Characteristics
- See Biologic therapy
- See Chemotherapy
- See Radiotherapy
Other: - No prior adjuvant limb perfusion after resection(s) that
rendered the patient disease-free with negative margins
- No concurrent IV antibiotics
Patient Characteristics:
Age: Performance status: Life expectancy: Hematopoietic: - WBC at least 3,000/mm3
- Platelet count at least 100,000/mm3
Hepatic: - SGOT no greater than 2 times upper limit of normal
(ULN)
- Bilirubin no greater than 2 times ULN
- LDH normal
- Alkaline phosphatase no greater than ULN (1.25
times ULN if negative CT scan or MRI of liver and negative bone scan or
negative PET scan)
Renal: - Creatinine no greater than 1.8 mg/dL
Other: - No active infection requiring treatment with IV
antibiotics
- No other significant medical, surgical, or psychiatric
condition or requirement for medication or treatment that would preclude
study compliance
- No diagnosis or evidence of organic brain syndrome or
significant impairment of basal cognitive function that would preclude study
compliance
- Able to self administer or arrange for administration of
subcutaneous injections
- No other malignancy within the past 5 years except any of the
following curatively treated cancers:
- Lobular carcinoma in situ of the breast
- Carcinoma in situ of the cervix
- Any other in situ cancer
- Atypical melanocytic hyperplasia
- Clark's level I melanoma (melanoma in situ)
- Basal cell or squamous cell skin cancer
- No autoimmune disorder
- No condition of immunosuppression
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and
for 18 months after study participation
Expected Enrollment 800A total of 800 patients will be accrued for this study within 4.4 years. Outcomes Primary Outcome(s)Overall survival at 2 years Two-year survival Time to progression
Outline This is a randomized, double-blind, placebo-controlled, multicenter
study. Patients are stratified by HLA-A2 status (positive vs negative), site
of metastases this occurrence (visceral vs nonvisceral vs visceral and
nonvisceral vs no metastases), and number of metastases this occurrence (1 vs 2 or 3 vs 4 or
more vs 0). Patients are assigned to one of two treatment groups based on HLA-A2
status. - Group A (HLA-A2 positive): Patients are randomized to 1 of 4 treatment
arms.
- Arm I: Patients receive sargramostim (GM-CSF) subcutaneously (SC)
daily on days 1-14. Patients receive peptide vaccination comprising the following 3 peptides: tyrosinase:368-376, gp100:209-217 (210M) antigen (gp100),
and MART-1:27-35 peptide. Each peptide is emulsified separately in
Montanide ISA-51 (ISA-51) and administered separately via 2 SC injections into
3 different sites on days 1 and 15 of course 1 and on day 1 of
subsequent courses.
- Arm II: Patients receive GM-CSF placebo SC on days 1-14.
Patients receive peptide vaccination as in arm I.
- Arm III: Patients receive GM-CSF as in arm I. Patients receive
peptide vaccination placebo comprising tyrosinase placebo, gp100 placebo,
and MART -1 placebo. Each peptide placebo is emulsified separately in
ISA-51 and administered separately via 2 SC injections into 3 different sites
on days 1 and 15 of course 1 and on day 1 of subsequent courses.
- Arm IV: Patients receive GM-CSF placebo as in arm II and peptide vaccination placebo as in arm III.
- Group B (HLA-A2 negative): Patients are randomized to 1 of 2 treatment
arms.
- Arm V: Patients receive GM-CSF SC as in arm I.
- Arm VI: Patients receive GM-CSF placebo as in arm II.
Treatment in both groups repeats every 4 weeks for 13 courses in the
absence of disease progression. Patients who develop unresectable recurrent
disease are taken off study, whereas those who develop resectable recurrent
disease undergo complete resection and may continue treatment on the arm to
which they were originally randomized for 6 additional courses or until they
complete 1 year of protocol treatment. Patients who develop a second
recurrence are taken off study. Patients are followed every 3 months for 2 years, every 6 months for 3
years, and then annually for up to 10 years. Published ResultsFalkson CI, Lawson DH, Ibrahim J, et al.: A randomised, placebo-controlled phase III trial of yeast derived GM-CSF vs. peptide vaccination vs. GM-CSF plus peptide vaccination vs. placebo in pts with ‘no evidence of disease’ after complete surgical resection of ‘locally advanced’ and / or stage IV melanoma. An Eastern Cooperative
group trial
. [Abstract] 4th International Conference on the Adjuvant Therapy of Malignant Melanoma, 15th-16th March 2002, London, UK A-I-03, 2002.
Trial Contact Information
Trial Lead Organizations Eastern Cooperative Oncology Group | | | David Lawson, MD, Protocol chair | | Ph: 404-778-4348; 888-946-7447 |
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Southwest Oncology Group | | | Kim Allyson Margolin, MD, Protocol chair | | | |
Related Information PDQ® clinical trial SWOG-S0008
Registry Information | | 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 | | Trial Start Date | | 1999-12-29 | | Registered in ClinicalTrials.gov | | NCT00005034 | | Date Submitted to PDQ | | 1999-12-23 | | Information Last Verified | | 2006-11-14 | | NCI Grant/Contract Number | | CA21115 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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