Combination Therapy of Topical Imiquimod Plus Multipeptide Vaccination for Cutaneous Metastases of Melanoma (MEL53)

This study has suspended participant recruitment.
(Study staff out on medical leave)
Sponsor:
Information provided by (Responsible Party):
Craig L Slingluff, Jr, University of Virginia
ClinicalTrials.gov Identifier:
NCT01264731
First received: December 20, 2010
Last updated: September 19, 2013
Last verified: September 2013
  Purpose

The purpose of the study is to determine 1) the safety of administration of topical 5% imiquimod cream with or without administration of a peptide-based vaccine in patients with cutaneous metastases of melanoma and 2) evaluate whether topical imiquimod at sites of melanoma metastasis, with or without vaccine, increases a) endothelial expression of E-selectin and b) T cell infiltration.


Condition Intervention
Melanoma
Biological: MELITAC 12.1
Drug: Imiquimod

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Combination Therapy of Topical Imiquimod Plus Multipeptide Vaccination for Cutaneous Metastases of Melanoma

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Safety: To determine the safety of administration of topical 5% imiquimod cream with or without administration of a peptide-based vaccine in patients with cutaneous metastases of melanoma. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Biologic: To evaluate whether topical imiquimod at sites of melanoma metastasis, with or without vaccine, increases a) endothelial expression of E-selectin and b) T cell infiltration. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: January 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: peptide vaccine plus imiquimod
Peptide Vaccine: Days 1, 8, 15, 36, 57, 78 Imiquimod: Applied daily on days 1-85.
Biological: MELITAC 12.1
Vaccine regimen: The vaccines will be administered in two treatment cycles. During cycle one, three vaccines will be administered over a 3-week period on days 1, 8, and 15. During cycle two, three vaccines will be administered over a 9-week period on days 36, 57, 78. Participants in cohort 1 will receive MELITAC 12.1 (100 mcg each of the12-MP and 200 mcg of Peptide-tet) administered subcutaneously (1 ml) and intradermally (1 ml) in Montanide ISA-51 VG adjuvant at a single vaccination site.
Drug: Imiquimod
Topical Imiquimod regimen: Beginning on day 1, patients in cohorts 1 and 2 will have one or more cutaneous melanoma metastases treated topically with 5% imiquimod cream, with a dose of 1 to 3 packets of imiquimod daily, (depending on the extent of cutaneous metastases). Each packet contains 250 mg of cream and may be used for a surface area of up to 20 cm2. The number of lesions that are treated will be dependent on the availability and size of the lesions. In addition, if available, at least two lesions will be followed without treatment with the plan that they will be excised at week 3 (day 22) and week 6 (day 43), respectively, as controls. Imiquimod will be applied daily for seven days each week for 12 weeks. One course of treatment will be three weeks in duration, with evaluation by a clinician after every treatment course.
Other Name: Aldara
Active Comparator: Imiquimod
Imiquimod: Applied daily on days 1-85.
Drug: Imiquimod
Topical Imiquimod regimen: Beginning on day 1, patients in cohorts 1 and 2 will have one or more cutaneous melanoma metastases treated topically with 5% imiquimod cream, with a dose of 1 to 3 packets of imiquimod daily, (depending on the extent of cutaneous metastases). Each packet contains 250 mg of cream and may be used for a surface area of up to 20 cm2. The number of lesions that are treated will be dependent on the availability and size of the lesions. In addition, if available, at least two lesions will be followed without treatment with the plan that they will be excised at week 3 (day 22) and week 6 (day 43), respectively, as controls. Imiquimod will be applied daily for seven days each week for 12 weeks. One course of treatment will be three weeks in duration, with evaluation by a clinician after every treatment course.
Other Name: Aldara

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participants with stage IIIB, IIIC or IV melanoma with cutaneous metastases.
  2. Patients must have adequate cutaneous metastases of melanoma readily accessible for biopsy to provide a minimum of 0.3 cm3 of tissue per biopsy (approximately 0.85 cm by 0.85 cm x 0.85 cm or five 2mm core biopsies) at each of three time points. Several scenarios may fulfill the tumor burden requirement. For example, a patient may have one large lesion from which core biopsies can be taken for the first and second biopsy time points and then the entire lesion excised for the final tissue sample. Other combinations are acceptable.
  3. The intent is to limit this study to patients with cutaneous melanoma metastasis rather than subcutaneous or lymph node metastasis because imiquimod may not penetrate to those deeper metastases.
  4. Patients may have had multiple primary melanomas.
  5. Patients may have had or may have a metastasis from a cutaneous primary site, mucosal primary site, ocular primary site, or unknown primary site.
  6. Patients who have had brain metastases may be eligible if they meet the following criteria

    • Patients with less than or equal to 5 metastases may be eligible as long as the following 3 criteria are true:
    • The brain metastases have been completely removed by surgery or have been treated completely by stereotactic radiotherapy. Stereotactic radiotherapy, such as gamma knife, can be used up to 1 week prior to study entry.
    • There has been no evident growth of any brain metastasis since treatment.
    • No metastasis greater than 2 cm at the time of protocol entry
    • Patients with greater than 5 metastases may be eligible if the above 3 criteria are met and if at least one year has elapsed since the last treatment.
  7. All participants must have ECOG performance status of 0 or 1 and ability and willingness to give informed consent
  8. Patients must have at least one intact axillary and/or inguinal lymph node basin. A patient with a prior lymph node biopsy may be a candidate if lymphoscintigraphy demonstrates intact drainage to a node in that basin. A lymphoscintigram may be performed during screening to ensure that there is drainage to a regional node from a planned vaccine site. If the lymphoscintigram is performed and a sentinel lymph node is not located, the patient will be ineligible for this study if no other vaccine sites are available.
  9. Laboratory parameters as follows: The following laboratory parameters will be required for all participants. If a lab value appears to be an error or a result of a transient or treatable condition, the investigator will use his/her clinical judgment to decide if the test may be repeated. The requirements for inclusion are as follows:

    • HLA-A1, -A2, -A3, or -A11+
    • ANC > 1000/mm3
    • Platelets > 100,000/mm3
    • Hgb ≥ 9 g/dL
    • HGBA1C < 7%
    • AST and ALT ≤ 2.5 x upper limits of normal (ULN)
    • Bilirubin ≤ 2.5 x ULN
    • Alkaline phosphatase ≤ 2.5 x ULN
    • Creatinine ≤ 1.5 x ULN
    • HIV negative (within 6 months of study entry)
    • Hepatitis C negative (within 6 months of study entry)
    • LDH up to 2 x ULN
  10. Patients must be 18 years or older at study entry

Exclusion Criteria:

  1. Patients who have had brain metastases unless they meet the criteria outlined above
  2. Patients who are currently receiving systemic cytotoxic chemotherapy, radiation, or other experimental therapy, or who have received this therapy within the preceding 4 weeks. Gamma knife or stereotactic radiosurgery may be administered within the prior 4 weeks, but must not be administered less than one week prior to study enrollment. Patients who are currently receiving nitrosoureas or who have received this therapy within the preceding 6 weeks.
  3. Patients will not be eligible if there is clinically detectable melanoma deemed likely by the investigator to require intervention during the first 12 weeks of the study that would require premature discontinuation. Examples for such circumstances may include untreated bone metastases at risk for fracture, and rapidly progressive low volume disease.
  4. Patients with known or suspected allergies to any component of the vaccine.
  5. Patients receiving the following medications at study entry or within the preceding 4 weeks are excluded:

    • Agents with putative immunomodulating activity (with the exception of non-steroidal anti-inflammatory agents and topical steroids
    • Allergy desensitization injections.
    • Systemic corticosteroids, administered parenterally or orally. Inhaled steroids (e.g. Advair®, Flovent®, Azmacort®) are not permitted. Topical corticosteroids are acceptable, including steroids with very low solubility administered nasally for local effects only (e.g. Nasonex®).
    • Any pharmacologic growth factors (e.g. GM-CSF, G-CSF, erythropoietin).
    • Interferon therapy.
    • Interleukin-2 or other interleukins.
    • Topical 5% Imiquimod cream: Patients must not have had imiquimod therapy to any body site within 4 weeks of study entry and must not have had any prior imiquimod therapy to the lesions to be treated, watched or biopsied on this present study. If imiquimod has been used in the past and either led to complete regression of the treated lesions, or those lesions have been removed surgically, then the patient may be eligible.
  6. Prior melanoma vaccinations may be an exclusion criterion in som circumstances:

    • Patients who have recurred or progressed either after or during administration of a melanoma vaccine may be eligible to enroll 12 weeks following their last vaccination.
    • Patients may have been vaccinated previously with peptide vaccines (including MELITAC 12.1 and similar vaccines) or with non-peptide vaccines.
  7. Pregnancy or the possibility of becoming pregnant during vaccine administration. Female patients of child-bearing potential must have a negative pregnancy test (urinary or serum beta-HCG) prior to administration of the first vaccine dose. Males and females must agree, in the consent form, to use effective birth control methods during the course of vaccination. Women must also not be breast feeding. This is consistent with existing standards of practice for vaccine and chemotherapy protocols.
  8. Patients in whom there is a medical contraindication or potential problem in complying with the requirements of the protocol, in the opinion of the investigator.
  9. Patients classified according to the New York Heart Association classification as having Class III or IV heart disease (Appendix 4).
  10. Patients with a body weight < 110 lbs because of the amount and frequency with which blood will be drawn
  11. Participants must not have had prior autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement. Participants with an active autoimmune disorder requiring these therapies are also excluded. The following will not be exclusionary:

    • The presence of laboratory evidence of autoimmune disease (e.g. positive ANA titer) without associated symptoms
    • Clinical evidence of vitiligo
    • Other forms of depigmenting illness
    • Mild arthritis requiring NSAID medications or no medical therapy
  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: NCT01264731

Locations
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Craig L Slingluff, M.D. University of Virginia
  More Information

No publications provided

Responsible Party: Craig L Slingluff, Jr, Professor of Surgery, Principal Investigator, University of Virginia Health System, Department of Surgery, Human Immune Therapy Center, University of Virginia
ClinicalTrials.gov Identifier: NCT01264731     History of Changes
Other Study ID Numbers: 15168
Study First Received: December 20, 2010
Last Updated: September 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Virginia:
melanoma
peptide vaccine
aldara
imiquimod
immunotherapy

Additional relevant MeSH terms:
Melanoma
Neoplasm Metastasis
Skin Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplastic Processes
Pathologic Processes
Neoplasms by Site
Skin Diseases
Imiquimod
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Interferon Inducers

ClinicalTrials.gov processed this record on August 28, 2014