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

NCT01264731 | Completed Phase 1 DMC

• 1 other identifier: 15168
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Melanoma

Keywords

melanoma; peptide vaccine; aldara; imiquimod; immunotherapy

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (1)

• 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.

  6 months

Study Arms (2)

peptide vaccine plus imiquimod

ACTIVE COMPARATOR

Peptide Vaccine: Days 1, 8, 15, 36, 57, 78 Imiquimod: Applied daily on days 1-85.

Biological: MELITAC 12.1; Drug: Imiquimod

Imiquimod

ACTIVE COMPARATOR

Imiquimod: Applied daily on days 1-85.

Drug: Imiquimod

Interventions

MELITAC 12.1 BIOLOGICAL

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.

peptide vaccine plus imiquimod

Imiquimod DRUG

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.

Also known as: Aldara

Imiquimod; peptide vaccine plus imiquimod

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with stage IIIB, IIIC or IV melanoma with cutaneous metastases.
• 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.
• 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.
• Patients may have had multiple primary melanomas.
• Patients may have had or may have a metastasis from a cutaneous primary site, mucosal primary site, ocular primary site, or unknown primary site.
• 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.
• All participants must have ECOG performance status of 0 or 1 and ability and willingness to give informed consent
• 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.
• HLA-A1, -A2, -A3, or -A11+
• ANC \> 1000/mm3

You may not qualify if:

• Patients who have had brain metastases unless they meet the criteria outlined above
• 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.
• 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.
• Patients with known or suspected allergies to any component of the vaccine.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• Tran CA, Lynch KT, Meneveau MO, Katyal P, Olson WC, Slingluff CL Jr. Intratumoral IFN-gamma or topical TLR7 agonist promotes infiltration of melanoma metastases by T lymphocytes expanded in the blood after cancer vaccine. J Immunother Cancer. 2023 Feb;11(2):e005952. doi: 10.1136/jitc-2022-005952.

  PMID: 36746511 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

Imiquimod

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Craig L Slingluff, M.D.

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery, Principal Investigator, University of Virginia Health System, Department of Surgery, Human Immune Therapy Center

Study Record Dates

• First Submitted: December 20, 2010
• First Posted: December 22, 2010
• Study Start: January 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: December 16, 2016

Record last verified: 2016-12

Locations

US (1)