MDACC Study Summary 2008-0416

Study Summary
No. 2008-0416:.......Melanoma......Richard Royal......Melanoma Medical Oncology

Study Summary Title



Study Summary Number:	2008-0416

Study Title:	Activation of pDCs at the Tumor and Vaccine Site with a TLR Agonist

Physician

New Patient Referral



Name:	Richard Royal	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Melanoma Medical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-2921 Contact us about clinical trials

General Information



Disease Group:	Melanoma	Supported By:	N/A

Phase of Study:	Phase II	Return Visit:	Every week for 8 weeks then every 4 weeks for 16 weeks.

Treatment Agents:	gp100 peptide MAGE-3 R848 Resiquimod (gel)	Home Care:	N/A

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:	N/A


Description/ Intervention:	The goal of this clinical research study is to learn if the vaccines, gp100(g209-2M), and MAGE-3, when given in combination with resiquimod (R848), can help to stimulate the immune system against melanoma.

Study Objectives / Outcomes

1.1 Primary Objective

To compare the ability of vaccines in combination with Toll Like Receptor (TLR) stimulation at the site of vaccine (R848; Resiquimod) to vaccines alone in the ability to enhance the generation of circulating antigen-specific T-cells (T-cell priming).

1.2 Secondary Objectives

A. To evaluate the ability of locally administered TLR agonist (R848 gel) to activate innate immune cells at the gp100(g209-2M) vaccine site

B. To evaluate the ability of R848 gel, administered at the tumor site

to:

i. Induce inflammation and upregulation of adhesion molecules on tumor vasculature

ii. Enhance T-cell infiltration into tumor

iii. Generate T-cells against additional tumor antigens, not present in the vaccine (i.e., antigen spreading).

iv. Mediate clinical response with measure of objective tumor response rate and progresison free surivival.

C. To assess the association between clinical response with laboratory parameters of T-cell priming, T-cell migration to tumor, and inflammation at the vaccine and tumor sites.

Study Status Information



Study Activation / Registration Date:	05/20/2010

IRB Review and Approval Date:	05/20/2010

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Open

Projected Accrual:	N/A

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) HLA-A*0201 positive (to enable immunization with the HLA class I restricted gp100(g209-2M) peptide). Stage IIB or IIC patients will be enrolled after review and approval by the PI. (a tool to determine the projected survival at 5 years, like, but not limited to, the nomogram at www.melanomaprognosis.org. If the projected survival is less than 50% at 5 years, then the patient is considered for enrollment. This is with the recognition that the adjuvant, if effective offers a significant impact in that group of stage II patients.)

2) Patients >/= 18 years old with histologically documented metastatic melanoma with a. (Metastatic disease cohort) Measurable disease, stage IIIB, IIIC (in transit lesions with or without nodal metastases) that includes lesions accessible for biopies or b. (Adjuvant cohort) subjects who are NED and stage III or IV. This includes patients with stage IV disease resected to NED. Stage IIB or IIC patients will be enrolled after review and approval by the PI.

3) Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

4) At least 4 biopsiable cutaneous lesions

5) White Blood Count (WBC) >/= 3000/mm^3 (part 1 & 2)

6) Platelet count >/= 90,000/mm^3 (part 1 & 2)

7) Serum alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) </= 3 X upper limit of normal (ULN) (part 1 & 2)

8) Total bilirubin </= 2 X ULN, except for patients with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl Total bilirubin </= 2 X ULN, except for patients with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl (part 1 & 2)

9) Seronegative for human immunodeficiency virus (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 may be less responsive to the experimental treatment and more susceptible to its toxicities.)

10) Negative pregnancy test for women of childbearing potential (WOCBP) A WOCBP has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses at any time in the preceding 12 consecutive months)

11) Patients of both gender must practice a barrier method of birth control while participating in this trial.

Exclusion Criteria:

1) Active autoimmune disease requiring active therapy with any form of steroid or immunosuppressive therapy or a documented history of any of the following: inflammatory bowel disease; regional enteritis; systemic lupus erythematosis; Sjogren's syndrome; inflammatory neurologic disorder such as multiple sclerosis; or any immune mediated disease that can cause life-threatening symptoms or severe organ/tissue damage in the opinion of the principle investigator.

2) Concurrent systemic or inhaled steroid therapy

3) Any form of active primary or secondary immunodeficiency

4) Prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, thyroid cancer (except anaplastic) or any cancer from which the patient has been disease-free for 2 years

5) History of immunization with gp100(g209-2M)

6) Active systemic infections requiring intravenous antibiotics

7) Women who are breastfeeding

8) Prior systemic therapy, radiation therapy or intracavitary surgery (intra-thoracic, intra-abdominal or intracranial) within 28 days of starting study treatment.

9) Patients on chronic anticoagulation such as Aspirin, Plavix, or Coumadin who cannot have anticoagulation held for procedures are not eligible due to the need for leukapheresis

Links

Registration Number: NCT00960752
Study Information on Clinical Trials Registry (clinicaltrials.gov)