Ignite Creation Date:
2024-05-05 @ 4:35 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00273910
Status:
COMPLETED
Last Update Posted:
2012-10-19
First Post:
2006-01-07
Brief Title:
Evaluation of the Impact of Adjuvants Accompanying Peptide Immunization in High-Risk Melanoma
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Evaluation of the Impact of Adjuvants Accompanying Peptide Immunization in High Risk Melanoma
Status:
COMPLETED
Status Verified Date:
2012-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will evaluate the immunization effects of a vaccine for patients who are at risk for recurrence of their skin cancer That is the risk of cancer is higher if melanoma has invaded deep into the skin or lymph nodes Currently the only therapy that the US Food and Drug Administration FDA has approved for preventing recurrence of melanoma is alpha-interferon But the research data are controversial In this study the vaccine to be used called gp100 contains a piece of a protein called a peptide which melanoma cancer cells produce
Patients 16 and older who have had confirmed melanoma surgically removed and whose tissue type is tested as being human leukocyte antigen serotype within HLA-A serotype group HLA-A2 through a specific blood test may be eligible for this study
Up to 132 participants will be enrolled There will be a physical examination and collection of blood samples for tests and making sure that x-rays and scans are current Patients will be randomly assigned to four groups Group 1 will receive the peptide with an adjuvant assistant oil-based liquid called Montanide ISA-51 as an injection in the thigh Group 2 will receive gp100 Montanide and a cream called imiquimod which the FDA has approved for treating genital warts and herpes but that may help immune cells in the skin to recognize the vaccine Imiquimod will be applied to the skin for 5 days Group 3 will receive gp100 mixed in salt water given as several mini-doses under the skin of the thigh Group 4 will also receive several mini-doses of gp100 mixed in saline as well as imiquimod cream applied to the skin for 5 days All patients will receive the gp100 every 3 weeks for 12 weeks Every dose is a cycle with four cycles considered a course of therapy If the melanoma does not return or patients do not experience side effects from this therapy then the courses of vaccine will repeated for up to 12 cycles of therapy 3 courses over 33 weeks Side effects of the peptide vaccination include local swelling swelling of local lymph nodes bruising and pain and redness at the injection sites There may be chills or fever Patients will be watched closely for such side effects
To study how the vaccine changes the action of cells in the immune system patients white blood cells lymphocytes will be obtained involving a separate informed consent The procedure called leukaphersis requires inserting a needle into the arm to obtain blood going into a machine which divides the blood into red cells plasma or the serum part and lymphocytes The lymphocytes are removed and the plasma and red cells returned to the patient through a second needle in the other arm Risks associated with the procedure include fainting which can be prevented by patients eating before coming to the lab and bleeding and infection at the needle site Patients will undergo leukapheresis will be done about four times before receiving the vaccine 3 weeks after the first four doses and then after 8 cycles and 12 cycles Patients assigned to the groups receiving imiquimod will be asked to record every time they apply that cream and describe any symptoms developed during the study All patients will be watched closely for any sign that their melanoma has returned Before and throughout the study multiple blood tests will be conducted
The vaccine Montanide and imiquimod may increase patients immune system in fighting off new tumors but that is not known now However the study may provide information that will be useful in treating melanoma patients in the future
Patients 16 and older who have had confirmed melanoma surgically removed and whose tissue type is tested as being human leukocyte antigen serotype within HLA-A serotype group HLA-A2 through a specific blood test may be eligible for this study
Up to 132 participants will be enrolled There will be a physical examination and collection of blood samples for tests and making sure that x-rays and scans are current Patients will be randomly assigned to four groups Group 1 will receive the peptide with an adjuvant assistant oil-based liquid called Montanide ISA-51 as an injection in the thigh Group 2 will receive gp100 Montanide and a cream called imiquimod which the FDA has approved for treating genital warts and herpes but that may help immune cells in the skin to recognize the vaccine Imiquimod will be applied to the skin for 5 days Group 3 will receive gp100 mixed in salt water given as several mini-doses under the skin of the thigh Group 4 will also receive several mini-doses of gp100 mixed in saline as well as imiquimod cream applied to the skin for 5 days All patients will receive the gp100 every 3 weeks for 12 weeks Every dose is a cycle with four cycles considered a course of therapy If the melanoma does not return or patients do not experience side effects from this therapy then the courses of vaccine will repeated for up to 12 cycles of therapy 3 courses over 33 weeks Side effects of the peptide vaccination include local swelling swelling of local lymph nodes bruising and pain and redness at the injection sites There may be chills or fever Patients will be watched closely for such side effects
To study how the vaccine changes the action of cells in the immune system patients white blood cells lymphocytes will be obtained involving a separate informed consent The procedure called leukaphersis requires inserting a needle into the arm to obtain blood going into a machine which divides the blood into red cells plasma or the serum part and lymphocytes The lymphocytes are removed and the plasma and red cells returned to the patient through a second needle in the other arm Risks associated with the procedure include fainting which can be prevented by patients eating before coming to the lab and bleeding and infection at the needle site Patients will undergo leukapheresis will be done about four times before receiving the vaccine 3 weeks after the first four doses and then after 8 cycles and 12 cycles Patients assigned to the groups receiving imiquimod will be asked to record every time they apply that cream and describe any symptoms developed during the study All patients will be watched closely for any sign that their melanoma has returned Before and throughout the study multiple blood tests will be conducted
The vaccine Montanide and imiquimod may increase patients immune system in fighting off new tumors but that is not known now However the study may provide information that will be useful in treating melanoma patients in the future
Detailed Description:
Background
A previous clinical trial has been conducted in the Surgery Branch National Cancer Institute NCI in which gp100 immunizations have been administered to patients with melanoma in the adjuvant setting In this prior protocol the peptide emulsified in Incomplete Freunds Adjuvant was administered subcutaneously using several different schedules and was well tolerated except for mild and transient erythema at the site of injection Each of the schedules provided successful immunization although the q3w schedule was the best tolerated locally and three courses of immunization appeared to be sufficient using this regimen An important finding from the adjuvant protocol however was the significant increase in immune precursors specifically reactive against peptide and tumor that occurred with increasing courses of immunization These findings have encouraged us to now further explore the optimal methods for generating immune precursors using the gp100209-217210M peptide by testing the impact of an additional immune adjuvant imiquimod reported to increase the immunizing potential of antigens as well as evaluate an alternate route of injection intradermal administration
Objectives
The primary objective of this trial is to evaluate the immunologic activity of immunization with four different preparations of the gp100209-217210M melanoma antigen peptide and potentially select one for further study
Eligibility
HLA-A 0201 patients age greater than or equal 16 years with primary melanomas with lesions that are ulcerated and greater than or equal 2mm or any lesions that are greater than or equal 40 mm in thickness or greater than or equal 1 positive lymph node or local recurrence or resected metastatic disease within 6 months of surgical resection will be considered Patients who have ocular or mucosal melanoma or who require systemic steroid therapy will be excluded The following patients will also be excluded have previously been immunized with gp100 have known hypersensitivity to any of the agents used in this study have previously received chemotherapy for treatment of melanoma or who are undergoing or have undergone in the past 3 weeks any systemic therapy except surgery for their cancer
Design
Patients will be randomized into one of the following four arms
1 gp100209-217210M peptide emulsified in MONTANIDE ISA-51 or Montanide ISA 51 VG injected subcutaneously on day one every three weeks 1 cycle for a total of twelve cycles 33 weeks
2 gp100209-217210M peptide emulsified in MONTANIDE ISA-51 or Montanide ISA 51 VG injected subcutaneously on day one every three weeks 1 cycle for a total of twelve cycles 33 weeks following the injection patients will apply imiquimod to the skin at the site of injection daily for 5 days
3 gp100209-217210M in 09 Sodium Chloride Injection injected intradermally on day one every three weeks 1 cycle for a total of twelve cycles 33 weeks
4 gp100209-217210M peptide in 09 Sodium Chloride Injection injected intradermally on day one every three weeks 1 cycle for a total of twelve cycles 33 weeks following the injection patients will apply imiquimod to the skin at the site of the injection daily for 5 days
Immunizations will be administered on an outpatient basis unless side effects or the patients clinical condition warrants hospitalization Patients will receive full clinical evaluation three weeks after 8 cycles and 12 cycles
Each of the arms will be conducted using a two-stage optimal design Since the primary objective is to select one regimen from among the four on the basis of the immune response this design allows there to be greater than 80 probability of correctly selecting the superior arm if there is either a tie in the number of immune responses or if there is at least one more immune response on one arm than the other three arms and if the true response rates are 15 15 15 and 35 Initially 19 patients will be enrolled in each arm and evaluated if 0 to 3 of 19 in an arm have an immune response to T2 cells pulsed with 001 M peptide after the 4th 8th and 12th cycles no further patients would be randomized to receive the peptide on that arm If at least four immunologic responses are noted after the 8th cycle then accrual to 33 patients would take place If all four arms need to be completed and 33 patients need to be completed in each arm a total of 132 patients are required
A previous clinical trial has been conducted in the Surgery Branch National Cancer Institute NCI in which gp100 immunizations have been administered to patients with melanoma in the adjuvant setting In this prior protocol the peptide emulsified in Incomplete Freunds Adjuvant was administered subcutaneously using several different schedules and was well tolerated except for mild and transient erythema at the site of injection Each of the schedules provided successful immunization although the q3w schedule was the best tolerated locally and three courses of immunization appeared to be sufficient using this regimen An important finding from the adjuvant protocol however was the significant increase in immune precursors specifically reactive against peptide and tumor that occurred with increasing courses of immunization These findings have encouraged us to now further explore the optimal methods for generating immune precursors using the gp100209-217210M peptide by testing the impact of an additional immune adjuvant imiquimod reported to increase the immunizing potential of antigens as well as evaluate an alternate route of injection intradermal administration
Objectives
The primary objective of this trial is to evaluate the immunologic activity of immunization with four different preparations of the gp100209-217210M melanoma antigen peptide and potentially select one for further study
Eligibility
HLA-A 0201 patients age greater than or equal 16 years with primary melanomas with lesions that are ulcerated and greater than or equal 2mm or any lesions that are greater than or equal 40 mm in thickness or greater than or equal 1 positive lymph node or local recurrence or resected metastatic disease within 6 months of surgical resection will be considered Patients who have ocular or mucosal melanoma or who require systemic steroid therapy will be excluded The following patients will also be excluded have previously been immunized with gp100 have known hypersensitivity to any of the agents used in this study have previously received chemotherapy for treatment of melanoma or who are undergoing or have undergone in the past 3 weeks any systemic therapy except surgery for their cancer
Design
Patients will be randomized into one of the following four arms
1 gp100209-217210M peptide emulsified in MONTANIDE ISA-51 or Montanide ISA 51 VG injected subcutaneously on day one every three weeks 1 cycle for a total of twelve cycles 33 weeks
2 gp100209-217210M peptide emulsified in MONTANIDE ISA-51 or Montanide ISA 51 VG injected subcutaneously on day one every three weeks 1 cycle for a total of twelve cycles 33 weeks following the injection patients will apply imiquimod to the skin at the site of injection daily for 5 days
3 gp100209-217210M in 09 Sodium Chloride Injection injected intradermally on day one every three weeks 1 cycle for a total of twelve cycles 33 weeks
4 gp100209-217210M peptide in 09 Sodium Chloride Injection injected intradermally on day one every three weeks 1 cycle for a total of twelve cycles 33 weeks following the injection patients will apply imiquimod to the skin at the site of the injection daily for 5 days
Immunizations will be administered on an outpatient basis unless side effects or the patients clinical condition warrants hospitalization Patients will receive full clinical evaluation three weeks after 8 cycles and 12 cycles
Each of the arms will be conducted using a two-stage optimal design Since the primary objective is to select one regimen from among the four on the basis of the immune response this design allows there to be greater than 80 probability of correctly selecting the superior arm if there is either a tie in the number of immune responses or if there is at least one more immune response on one arm than the other three arms and if the true response rates are 15 15 15 and 35 Initially 19 patients will be enrolled in each arm and evaluated if 0 to 3 of 19 in an arm have an immune response to T2 cells pulsed with 001 M peptide after the 4th 8th and 12th cycles no further patients would be randomized to receive the peptide on that arm If at least four immunologic responses are noted after the 8th cycle then accrual to 33 patients would take place If all four arms need to be completed and 33 patients need to be completed in each arm a total of 132 patients are required
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 06-C-0069 | None | None | None |