Phase I Protocol for the Evaluation of the Safety and Immunogenicity of Vaccination With a Synthetic Melanoma Peptide in Patients With High Risk Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Safety: Grade 3 Adverse Events
研究概览
简要总结
RATIONALE: Vaccines made from peptide 946 may make the body build an immune response to kill tumor cells. Combining these vaccines with proteins from the tetanus vaccine, and/or with either QS21 or Montanide ISA-51 may be an effective treatment for metastatic melanoma.
PURPOSE: Randomized phase I trial to study the effectiveness of vaccines made from peptide 946 with or without tetanus peptide, QS21, or Montanide ISA-51 in treating patients with metastatic melanoma that cannot be surgically removed or with melanoma that is likely to recur.
详细描述
OBJECTIVES:
I. Determine the safety of peptide 946 melanoma vaccine (peptide 946), peptide 946 combined with tetanus peptide melanoma vaccine, or peptide 946-tetanus peptide conjugate in patients with high risk melanoma.
II. Determine the immunogenicity of peptide 946 melanoma vaccine (peptide 946), peptide 946 combined with tetanus peptide melanoma vaccine, or peptide 946-tetanus peptide conjugate in patients with high risk melanoma.
OUTLINE: This is a randomized, open-label study. Patients are randomized to 1 of 6 treatment arms: Arm I: Patients receive peptide 946 melanoma vaccine (peptide 946) emulsified with QS21 subcutaneously (SQ). Arm II: Patients receive peptide 946 emulsified with Montanide ISA-51 (ISA-51) SQ. Arm III: Patients receive peptide 946 combined with tetanus peptide melanoma vaccine (tetanus peptide) emulsified with QS21 SQ. Arm IV: Patients receive peptide 946 combined with tetanus peptide emulsified with ISA-51 SQ. Arm V: Patients receive peptide 946-tetanus peptide conjugate emulsified with QS21 SQ. Arm VI: Patients receive peptide 946-tetanus peptide conjugate emulsified with ISA-51 SQ. Initially, 4 patients are randomized to Arm I and 4 patients are randomized to Arm II. If no dose limiting toxicities are observed in these patients, then additional patients are randomized to arms III-VI. Patients in each arm receive vaccine on day 0 and at months 1, 2, 3, 6, 9, and 12. Patients are followed at 6 and 12 months.
PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed unresectable metastatic melanoma (AJCC stage III or IV) OR resected melanoma with high risk of recurrence or mortality (stage IIB and above)
- •Age: 18 to 79
- •Performance status: ECOG 0-2
- •Life expectancy: Greater than 12 months
- •Hematopoietic: Absolute neutrophil count greater than 1,000/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 9 g/dL
- •Hepatic: AST and ALT no greater than 2.5 times upper limit of normal (ULN) Bilirubin no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN
- •Renal: Creatinine no greater than 1.5 times ULN
排除标准
- •patients currently receiving cytotoxic chemotherapy or who have received that therapy within the preceding 3 months
- •known or suspected allergies to any component of the treatment vaccine
- •unresectable tumor llikely to cause symptoms and for which therapy is anticipated within 3 months.
- •receiving acute treatment for seriouis infection within 14 days.
- •Patients with bulky disease, or with multiple brain metastases, but solitary brain metastases treated successfully with surgery or gamma knife may be eligible.
- •Any of the following with 3 months:
- •agentes with putative immunomodulating activity (except NSAIDs)
- •allergy desensitizing injections
- •other investigational agents
- •interferons
- •corticosteroids
- •any growth factors
- •prior melanoma vaccinations
- •pregnancy or the possibility of becoming pregnant on study
- •medical contraindication or potential problems in complying with the requirements of the protocol.
研究组 & 干预措施
Group 2. p946 plus IFA
100 mcg peptide gp100 [280-288] plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
干预措施: IFA (incomplete Freund's adjuvant) (Biological)
Group 3: p946 plus Tet-p plus QS-21
100 mcg peptide gp100 [280-288],190 mcg tetanus peptide, plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
干预措施: Tet-p (Biological)
Group 4. p946, Tet-p plus IFA
100 mcg peptide gp100 [280-288], 190 mcg tetanus peptide, plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
干预措施: IFA (incomplete Freund's adjuvant) (Biological)
Group 4. p946, Tet-p plus IFA
100 mcg peptide gp100 [280-288], 190 mcg tetanus peptide, plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
干预措施: Tet-p (Biological)
Group 5: p946/Tet-p plus QS-21
282 mcg gp100 [280-288]/tetanus peptide conjugate, plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
干预措施: p946/tet-p (Biological)
Group 6. p946/Tet-p plus IFA
282 mcg gp100 [280-288]/tetanus peptide conjugate, plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
干预措施: IFA (incomplete Freund's adjuvant) (Biological)
Group 6. p946/Tet-p plus IFA
282 mcg gp100 [280-288]/tetanus peptide conjugate, plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
干预措施: p946/tet-p (Biological)
Group 5: p946/Tet-p plus QS-21
282 mcg gp100 [280-288]/tetanus peptide conjugate, plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
干预措施: QS21 (Biological)
Group 4. p946, Tet-p plus IFA
100 mcg peptide gp100 [280-288], 190 mcg tetanus peptide, plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
干预措施: p946 (Biological)
Group 3: p946 plus Tet-p plus QS-21
100 mcg peptide gp100 [280-288],190 mcg tetanus peptide, plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
干预措施: p946 (Biological)
Group 3: p946 plus Tet-p plus QS-21
100 mcg peptide gp100 [280-288],190 mcg tetanus peptide, plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
干预措施: QS21 (Biological)
Group 2. p946 plus IFA
100 mcg peptide gp100 [280-288] plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
干预措施: p946 (Biological)
Group 1: peptide 946 plus QS-21
100 mcg peptide gp100 [280-288] plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
干预措施: p946 (Biological)
Group 1: peptide 946 plus QS-21
100 mcg peptide gp100 [280-288] plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
干预措施: QS21 (Biological)
结局指标
主要结局
Safety: Grade 3 Adverse Events
时间窗: Up to 24 months after last vaccine
Adverse events are monitored according to NCI/DCT Common Toxicity Criteria
次要结局
- Immunogenicity of Each Vaccine Regimen(up to 12 months since enrollment)
研究者
Craig L Slingluff, Jr
Professor of Surgery
University of Virginia