Melanoma Vaccine With Peptides and Leuprolide

Condition(s) targeted: Melanoma

Intervention: Leuprolide (Drug); GP100: 209-217(210M) Peptide (Biological); MAGE-3 Peptide (Biological)

Phase: Phase 2

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Patrick Hwu, MD, Principal Investigator, Affiliation: U.T.M.D. Anderson Cancer Center

Overall contact:
Patrick Hwu, MD, Phone: 713-563-1727, Email: phwu@mdanderson.org

Primary Objective:

1. To compare the tumor-specific immune responses to melanoma-specific peptide vaccines, gp100 and MAGE-3 in the presence or absence of a luteinizing hormone-releasing hormone (LHRH) agonist-Leuprolide, in patients with stage IIb and III melanoma, uveal melanoma or stage IV melanoma that the metastatic lesion(s) has been surgically removed.

Secondary Objectives:

1. To evaluate the kinetics of enhanced thymic activity measured by TREC analysis and flow cytometric analysis following sex hormone ablation by Leuprolide in melanoma patients.

2. To assess whether there are significant differences in overall quality of life (QOL) between patients receiving Leuprolide to those not receiving leuprolide.

Official title: Study of the Modulatory Activity of an LHRH-Agonist (Leuprolide) on Melanoma Peptide Vaccines as Adjuvant Therapy in Melanoma Patients

Study design: Prevention, Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study

Primary outcome: To learn if the drug leuprolide will increase the level of immune cells in your body.

Secondary outcome: To learn if this drug given together with melanoma vaccines (gp100 and MAGE-3) can improve the ability of tumor fighting immune cells (T cells) to fight melanoma cells.

Detailed description: The incidence of melanoma is rising in the US. Patients with stage IIb-IV melanoma have significant risk of recurrence after definitive or palliative surgery. With the discovery of numerous antigens for melanoma capable of recognition by T-cells, current goals are focused on defining the best approaches to immunize melanoma patients with these antigens in order to elicit tumor-specific immune responses, and ultimately tumor regression or prevention of disease recurrence. We have previously shown that melanoma patients can be immunized with peptides derived from melanoma associated antigens, such as gp100, resulting in increased numbers of circulating T-cells capable of recognizing the tumor. However, maximum immune response to the vaccines required up to a year of immunizations and new strategies are needed for more efficient vaccination. One potential strategy is to increase thymic activity. T-cells develop in the thymus, which involutes with progressively diminished activity following puberty. This might adversely affect the ability to immunize adults against specific antigens. In addition, aging has been correlated with decreased immune responses against new antigens. Therefore, methods to enhance thymic activity in adults may potentiate antigen-specific immune responses. Ablation of sex steroids has been shown to increase thymic activity. In murine models, surgical castration of aged mice can restore the responsiveness to herpes simplex virus to levels similar to those seen in young mice. Sex steroid ablation by the LHRH-agonist Leuprolide in elderly men for prostate cancer resulted in increased thymic dependent T cell production, particularly naïve (TREC+) CD4+ T cells. Regeneration of adult thymic function by sex steroid ablation therefore may provide a means to improve antitumor T cell immune responses. Our hypothesis is that sex hormone blockade will result in enhanced thymic activity in melanoma patients that will lead to improved anti-tumor T cell responses following antigen-specific immunization.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion:

1. HLA-A *0201 positive

2. Patients >/= 18 years old with histologically documented diagnosis of stage IIb-IV melanomas and are clinically rendered free of disease after surgery

3. Uveal melanoma patients following definitive treatment of radiation therapy and/or enucleation.

4. Karnofsky Performance Scale >/= 60%.

5. WBC >/= 3000/mm^3.

6. Platelet count >/= 90,000mm^3.

7. Serum creatinine 8. Serum ALT 9. Total bilirubin equal or less than 2X upper limit of normal (ULN)), except for patient with Gilbert's syndrome who must have a total bilirubin less than 3. 0mg/dl.

10. Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)

11. Negative pregnancy test by serum or urine b-HCG test for women who have menstruation in the past 12 months and without sterilization surgery.

12. Unless surgically sterile by bilateral tubal-ligation or vasectomy of partner(s), the subject agrees to continue to use a barrier method of contraception throughout the study such as: condom, or diaphragm, or sponge plus spermicide. Abstinence is an acceptable form of birth control.

Exclusion:

1. Prior systemic therapy (including immunomodulate agents), radiation or surgery requiring general anesthesia for melanoma within 28 days of starting study treatment.

2. Autoimmune diseases.

3. Concurrent systemic or inhaled steroid therapy.

4. Any form of active primary or secondary immunodeficiency.

5. History of immunization with gp100 or MAGE-3.

6. Prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, surgically treated Stage I or II cancer from which the patient is currently in complete remission (at least for 5 years), or any other cancer from which the patient has been disease-free for 5 years.

7. Received a LHRH agonist within the past 5 years.

8. Use of oral contraceptive, hormone replacement therapy or androgen preparations.

9. Hypersensitivity to gonadotropin-releasing hormone analogues.

10. Active systemic infections requiring intravenous antibiotics.

11. Lactating women or women planning lactation during the study.

Patrick Hwu, MD, Phone: 713-563-1727, Email: phwu@mdanderson.org

U.T.M.D. Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Patrick Hwu, MD, Principal Investigator

UT MD Anderson Cancer Center

Starting date: November 2005
Last updated: October 30, 2008