Vaccine Therapy in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Melanoma

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00398073
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 35
• Location: 1
• Arms: 2
• Duration (Months): 53
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

RATIONALE: Vaccines made from DNA may help the body build an effective immune response to kill tumor cells. Giving the vaccine in different ways may make a stronger immune response and kill more tumor cells.

PURPOSE: This randomized clinical trial is studying two different ways of giving vaccine therapy to compare how well they work in treating patients with stage IIB, stage IIC, stage III, or stage IV melanoma.

Condition or Disease	Intervention/Treatment	Phase
Intraocular Melanoma; Melanoma (Skin)	Biological: mouse gp100 plasmid DNA vaccine; Device: The Dermal PowderMed® devices; Other: intramuscularly (IM injection)	Phase 1

Detailed Description

OBJECTIVES:

Primary

• Evaluate the safety and feasibility of particle-mediated epidermal delivery (PMED) immunization comprising mouse gp100 plasmid DNA vaccine in patients with stage IIB, IIC, III, or IV melanoma.

• Compare the immunologic response induced with PMED vs intramuscular jet injection methods of vaccination in these patients.

Secondary

• Observe patients with measurable tumor for evidence of any antitumor response generated after vaccination.

• Assess for disease relapse in patients treated with this vaccine.

OUTLINE: This is a randomized, pilot study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive mouse gp100 plasmid DNA vaccine by particle-mediated epidermal delivery on days 1, 3, 5, 8, 22, 24, 26, 29, 43, 45, 47, 50, 64, 66, 68, and 71.

• Arm II: Patients receive mouse gp100 plasmid DNA vaccine by intramuscular jet injection on days 1, 3, 5, 8, 22, 24, 26, 29, 43, 45, 47, 50, 64, 66, 68, and 71.

After completion of study treatment, patients are followed periodically for 1 year.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Injection of AJCC Stage IIB, IIC, III and IV Melanoma Patients With Mouse gp100 DNA: A Pilot Study to Compare Intramuscular Jet Injection With Particle Mediated Delivery
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mouse gp100 DNA via PMED patients will be randomized to mouse gp100 DNA delivered via gold particles using the PowderMed delivery system (ND10, described above). Two actuations/day will be administered every two weeks for 4 months for a total of 16 actuations. Each actuation consists of 2 μg of plasmid DNA coated onto 1000 μg of gold. The total dose of plasmid DNA given will be 32 μg DNA on 16,000 μg gold.	Biological: mouse gp100 plasmid DNA vaccine; Device: The Dermal PowderMed® devices
Experimental: mouse gp100 DNA injections intramuscularly patients will be injected with 1000 μg of mouse gp100 plasmid DNA intramuscularly. Two injections/day will be administered every two weeks for 4 months (4000 ug of mouse gp100 plasmid/month) for 16 vaccinations.	Biological: mouse gp100 plasmid DNA vaccine; Other: intramuscularly (IM injection)

Outcome Measures

Primary Outcome Measures

1. Number of Patients Evulated for Toxicity and Safety [2 years]

   All toxicity will be graded according to the National Cancer Institute (NCI) Common Toxicity Criteria v3.0.

2. Number of Participants With a T-cell Response [2 years]

   T-cell response: Peripheral blood lymphocytes will be tested for reactivity against gp100 using an IFN-y ELISPOT, intracellular cytokine staining or MHC tetramer assay. If T-cell reactivity is induced, additional samples may be drawn to determine the duration of this reactivity. Follow-up blood samples require only 20-30 ml. MHC tetramer assays and intracellular flow cytometry studies may also be performed.

Secondary Outcome Measures

1. Number of Participants With Response [2 years]

   In patients with measurable disease, the RECIST criteria for anti-tumor effect will be used. Lesions will be defined as measurable if they can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm by spiral CT scan.Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant melanoma

• Stage IIB, IIC, III, or IV disease

• Patients free of disease after surgical resection must meet 1 of the following criteria:

• Refused high-dose interferon alfa

• Recurrence while on interferon alfa

• Patients with stage IIB, IIC, or III disease must have already undergone initial standard therapy (i.e., surgery) for the disease

• Choroidal (uveal) melanoma allowed provided 1 of the following criteria is met:

• Basal diameter > 16 mm

• Basal height > 8 mm

• Involvement of the ciliary body with tumor

• HLA-A*0201 positive

• Negative serum antidouble-stranded DNA antibody screen

• No known brain metastases

PATIENT CHARACTERISTICS:

• Karnofsky performance status 80-100%

• Platelet count ≥ 100,000/mm^3

• Absolute neutrophil count ≥ 1,500/mm^3

• WBC ≥ 3,000/mm^3

• Lactic dehydrogenase ≤ 2 times upper limit of normal (ULN)

• Creatinine ≤ 2.0 mg/dL

• Bilirubin ≤ 2.5 times ULN

• Albumin ≥ 3.5 mg/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Weight ≥ 25 kg

• No preexisting choroidal eye disease

• No serious underlying medical conditions that could be exacerbated by study participation (i.e., active infections requiring antimicrobial drugs or active bleeding)

• No allergy to gold (i.e., gold jewelry)

• No evidence of any condition at the proposed site(s) of vaccine administration that might interfere with the interpretation of local skin reactions, including any of the following:

• Damaged skin

• Moles

• Scars

• Tattoos

• Marks

• No prior medical condition or use of medication (e.g., corticosteroids) that might make it difficult for the patient to complete the full course of treatment or to respond immunologically to vaccines

• No history or evidence (within the past 5 years) of a physician-diagnosed chronic or recurrent inflammatory skin disease at the proposed site of vaccine administration, including any of the following:

• Psoriasis

• Eczema

• Atopic dermatitis

• Hypersensitivity

• No history of keloid formation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 4 weeks since prior chemotherapy, immunotherapy, or radiotherapy (6 weeks for nitrosoureas) and recovered

• No prior immunization with any class of vaccine containing gp100 peptide

• No other concurrent investigational agents

• No other concurrent systemic therapy or radiotherapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jedd D. Wolchok, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00398073
• Other Study ID Numbers: 06-113; MSKCC-06113
• First Posted: Nov 10, 2006
• Last Update Posted: Mar 16, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by Memorial Sloan Kettering Cancer Center: stage II melanoma; stage III melanoma; stage IV melanoma; recurrent melanoma; ciliary body and choroid melanoma, medium/large size; ciliary body and choroid melanoma, small size; recurrent intraocular melanoma; metastatic intraocular melanoma
• Additional relevant MeSH terms: Melanoma

Study Results

Participant Flow

Arm/Group Title	1_Particle-medicated Epidermal Delivery Group (Gene Gun)	2_IM Injection (Bioinjector)
Arm/Group Description	patients will be randomized to mouse gp100 DNA delivered via gold particles using the PowderMed delivery system (ND10, described above). Two actuations/day will be administered every two weeks for 4 months for a total of 16 actuations. Each actuation consists of 2 μg of plasmid DNA coated onto 1000 μg of gold. The total dose of plasmid DNA given will be 32 μg DNA on 16,000 μg gold. mouse gp100 plasmid DNA vaccine	patients will be injected with 1000 μg of mouse gp100 plasmid DNA intramuscularly. Two injections/day will be administered every two weeks for 4 months (4000 ug of mouse gp100 plasmid/month) for 16 vaccinations. mouse gp100 plasmid DNA vaccine
Period Title: Overall Study
STARTED	18	17
COMPLETED	17	17
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	1_Particle-medicated Epidermal Delivery Group (Gene Gun)	2_IM Injection (Bioinjector)	Total
Arm/Group Description	patients will be randomized to mouse gp100 DNA delivered via gold particles using the PowderMed delivery system (ND10, described above). Two actuations/day will be administered every two weeks for 4 months for a total of 16 actuations. Each actuation consists of 2 μg of plasmid DNA coated onto 1000 μg of gold. The total dose of plasmid DNA given will be 32 μg DNA on 16,000 μg gold. mouse gp100 plasmid DNA vaccine	patients will be injected with 1000 μg of mouse gp100 plasmid DNA intramuscularly. Two injections/day will be administered every two weeks for 4 months (4000 ug of mouse gp100 plasmid/month) for 16 vaccinations. mouse gp100 plasmid DNA vaccine	Total of all reporting groups
Overall Participants	17	17	34
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 70.6%	11 64.7%	23 67.6%
>=65 years	5 29.4%	6 35.3%	11 32.4%
Sex: Female, Male (Count of Participants)
Female	2 11.8%	6 35.3%	8 23.5%
Male	15 88.2%	11 64.7%	26 76.5%
Region of Enrollment (participants) [Number]
United States	17 100%	17 100%	34 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Evulated for Toxicity and Safety
Description	All toxicity will be graded according to the National Cancer Institute (NCI) Common Toxicity Criteria v3.0.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1_Particle-medicated Epidermal Delivery Group (Gene Gun)	2_IM Injection (Bioinjector)
Arm/Group Description	patients will be randomized to mouse gp100 DNA delivered via gold particles using the PowderMed delivery system (ND10, described above). Two actuations/day will be administered every two weeks for 4 months for a total of 16 actuations. Each actuation consists of 2 μg of plasmid DNA coated onto 1000 μg of gold. The total dose of plasmid DNA given will be 32 μg DNA on 16,000 μg gold. mouse gp100 plasmid DNA vaccine	patients will be injected with 1000 μg of mouse gp100 plasmid DNA intramuscularly. Two injections/day will be administered every two weeks for 4 months (4000 ug of mouse gp100 plasmid/month) for 16 vaccinations. mouse gp100 plasmid DNA vaccine
Measure Participants	17	17
Number [participants]	17 100%	17 100%

2. Primary Outcome

Title	Number of Participants With a T-cell Response
Description	T-cell response: Peripheral blood lymphocytes will be tested for reactivity against gp100 using an IFN-y ELISPOT, intracellular cytokine staining or MHC tetramer assay. If T-cell reactivity is induced, additional samples may be drawn to determine the duration of this reactivity. Follow-up blood samples require only 20-30 ml. MHC tetramer assays and intracellular flow cytometry studies may also be performed.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1_Particle-medicated Epidermal Delivery Group (Gene Gun)	2_IM Injection (Bioinjector)
Arm/Group Description	patients will be randomized to mouse gp100 DNA delivered via gold particles using the PowderMed delivery system (ND10, described above). Two actuations/day will be administered every two weeks for 4 months for a total of 16 actuations. Each actuation consists of 2 μg of plasmid DNA coated onto 1000 μg of gold. The total dose of plasmid DNA given will be 32 μg DNA on 16,000 μg gold. mouse gp100 plasmid DNA vaccine	patients will be injected with 1000 μg of mouse gp100 plasmid DNA intramuscularly. Two injections/day will be administered every two weeks for 4 months (4000 ug of mouse gp100 plasmid/month) for 16 vaccinations. mouse gp100 plasmid DNA vaccine
Measure Participants	17	17
Number [participants]	17 100%	17 100%

3. Secondary Outcome

Title	Number of Participants With Response
Description	In patients with measurable disease, the RECIST criteria for anti-tumor effect will be used. Lesions will be defined as measurable if they can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm by spiral CT scan.Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1_Particle-medicated Epidermal Delivery Group (Gene Gun)	2_IM Injection (Bioinjector)
Arm/Group Description	patients will be randomized to mouse gp100 DNA delivered via gold particles using the PowderMed delivery system (ND10, described above). Two actuations/day will be administered every two weeks for 4 months for a total of 16 actuations. Each actuation consists of 2 μg of plasmid DNA coated onto 1000 μg of gold. The total dose of plasmid DNA given will be 32 μg DNA on 16,000 μg gold. mouse gp100 plasmid DNA vaccine	patients will be injected with 1000 μg of mouse gp100 plasmid DNA intramuscularly. Two injections/day will be administered every two weeks for 4 months (4000 ug of mouse gp100 plasmid/month) for 16 vaccinations. mouse gp100 plasmid DNA vaccine
Measure Participants	17	17
Number [participants]	17 100%	17 100%

Adverse Events

Arm/Group Title	1_Particle-medicated Epidermal Delivery Group (Gene Gun)		2_IM Injection (Bioinjector)
Arm/Group Description	patients will be randomized to mouse gp100 DNA delivered via gold particles using the PowderMed delivery system (ND10, described above). Two actuations/day will be administered every two weeks for 4 months for a total of 16 actuations. Each actuation consists of 2 μg of plasmid DNA coated onto 1000 μg of gold. The total dose of plasmid DNA given will be 32 μg DNA on 16,000 μg gold. mouse gp100 plasmid DNA vaccine		patients will be injected with 1000 μg of mouse gp100 plasmid DNA intramuscularly. Two injections/day will be administered every two weeks for 4 months (4000 ug of mouse gp100 plasmid/month) for 16 vaccinations. mouse gp100 plasmid DNA vaccine
All Cause Mortality
	1_Particle-medicated Epidermal Delivery Group (Gene Gun)		2_IM Injection (Bioinjector)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	1_Particle-medicated Epidermal Delivery Group (Gene Gun)		2_IM Injection (Bioinjector)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/17 (17.6%)		1/17 (5.9%)
Blood and lymphatic system disorders
Edema: limb	1/17 (5.9%)		0/17 (0%)
General disorders
Pain - Chest/thorax NOS	0/17 (0%)		1/17 (5.9%)
Immune system disorders
Allergy/Immunology, other	1/17 (5.9%)	1	0/17 (0%)	0
Respiratory, thoracic and mediastinal disorders
Allergy/Immunology, other	1/17 (5.9%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	1_Particle-medicated Epidermal Delivery Group (Gene Gun)		2_IM Injection (Bioinjector)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/17 (29.4%)		5/17 (29.4%)
Hepatobiliary disorders
Bilirubin (hyperbilirubinemia)	2/17 (11.8%)		3/17 (17.6%)
Metabolism and nutrition disorders
AST, SGOT	1/17 (5.9%)		0/17 (0%)
Glucose, high (hyperglycemia)	3/17 (17.6%)		3/17 (17.6%)
Potassium, high (hyperkalemia)	1/17 (5.9%)		0/17 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.