MDACC Study Summary 2005-0070

Study Summary
No. 2005-0070:.......Melanoma......Merrick I. Ross......Surgical Oncology

Study Summary Title



Study Summary Number:	2005-0070

Study Title:	A MULTICENTER TRIAL TO EVALUATE THE EFFECTS OF ADMINISTRATION OF CYCLOPHOSPHAMIDE AND MELANOMA-DERIVED HELPER PEPTIDES ON THE IMMUNOGENICITY OF A CLASS I MHC-RESTRICTED PEPTIDE-BASED VACCINE IN PARTICIPANTS WITH RESECTED MELANOMA

Physician

New Patient Referral



Name:	Merrick I. Ross	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

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

Phone:	713-792-6940 Contact us about clinical trials

General Information



Disease Group:	Melanoma	Supported By:	N/A

Phase of Study:	Phase I/Phase II	Return Visit:	Evaluations will be performed on days 1, 8, 15, 22, 29, 36, 43, 50, weeks 12, 26, 39, 52, and at 13 and 24 months. Note: CBC with differential scheduled for Day -8 is not required if one has been performed Ł 7 days prior.

Treatment Agents:	Cyclophosphamide Peptide Vaccine	Home Care:	N/A

Treatment Loc:	Independent Multicenter Arrangements

Estimated Length of Stay in Houston:	N/A


Description/ Intervention:	The goal of this clinical research study is to learn if an experimental vaccine is safe when given to participants with or without chemotherapy. Researchers also want to learn if the vaccine will cause an immune response when given with or without chemotherapy.

Study Objectives / Outcomes

Primary:
(1) to determine the magnitude of immune responses against the 12-MP when administered in conjunction with a tetanus toxoid-derived helper peptide or 6-MHP with and without the addition of cyclophosphamide
(2) to determine whether the administration of 12 melanoma peptides comprised of class I MHC-restricted epitopes (12-MP) in conjunction with 6 melanoma-derived class II MHC-restricted helper peptides (6-MHP) is safe
(3) to determine whether the administration of cyclophosphamide (Cytoxan Ž) prior to administration of a peptide-based vaccine is safe

Secondary:
(1) to determine the response rate and persistence of immune responses against the 12-MP when administered in conjunction with a tetanus toxoid-derived helper peptide or 6-MHP with and without the addition of cyclophosphamide
(2) to determine the magnitude of immune responses against the tetanus toxoid-derived helper peptide or 6-MHP with and without the addition of cyclophosphamide
(3) to determine the response rate and persistence of immune responses against the tetanus toxoid-derived helper peptide or 6-MHP with and without the addition of cyclophosphamide
(4) to determine DTH responses to the peptide components of the vaccine
(5) to obtain preliminary estimates of disease-free survival

Study Status Information



Study Activation / Registration Date:	05/19/2005

IRB Review and Approval Date:	04/06/2005

Study Type:	Therapeutic

Recruitment Status:	Closed

Projected Accrual:	173

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) Participants with stage IIB, IIC, III or IV melanoma that have no clinical or radiological evidence of disease (NED) after surgical resection or stereotactic radiosurgery. These participants may have had cutaneous or mucosal primary melanoma, or an unknown primary melanoma. Staging must be confirmed by cytological or histological examination. Staging of cutaneous melanoma will be based on the revised AJCC staging system.

2) Participants will be required to have radiological studies to rule out radiologically evident disease. Required studies include: (1) Chest x-ray or chest CT scan; (2) Abdominal and pelvic CT scan; (3) Head CT scan or MRI; (4) PET/CT fusion scan may replace scans of the chest, abdomen, and pelvis.

3) Participants who have had brain metastases will be eligible if all of the following are true: (1) The total number of brain metastases ever </= 3; (2) Each brain metastasis must have been completely removed by surgery or each unresected brain metastasis must have been treated with stereotactic radiosurgery; (3) There has been no evident growth of any brain metastasis since treatment; (4) No brain metastasis is > 2 cm in diameter at the time of randomization.

4) The most recent surgical resections or gamma-knife therapy for malignant melanoma must have been completed greater than or equal to 1 week and less than or equal to 6 months prior to randomization.

5) The interferon education packet must be completed satisfactorily for those who are eligible for, but refuse, interferon therapy.

6) Participants who are not candidates for interferon for the following reasons do NOT need to complete an interferon education packet; 1) Active ischemic heart disease or cerebrovascular disease; 2) Anginal syndrome requiring ongoing medications or history of myocardial infarction or arrhythmia disorder; 3) History of treatment for depression, active depression, or other psychiatric disorder; 4) Autoimmune disorders.

7) Continued from inclusion #6 - Participants who are not candidates for interferon for the following reasons do NOT need to complete an interferon education packet; 5)Hypersensitivity to interferon-alpha or any component associated with interferon therapy; 6) Debilitating medical conditions such as severe pulmonary disease or severe diabetes mellitus; 7) Thyroid abnormalities, where thyroid function cannot be maintained in the normal range without medication.

8) Continued from inclusion # 7 - Participants who are not candidates for interferon for the following reasons do NOT need to complete an interferon education packet; 8) Resected stage IV melanoma; 9) Discontinued interferon therapy due to the occurrence of a major toxicity that has been documented by the treating physician; 10) Experienced tumor progression while on interferon or after completing interferon therapy.

9) All participants must have: 1) ECOG performance status of 0 or 1; 2) Ability and willingness to give informed consent.

10) Laboratory parameters as follows: (1) HLA-A1, -A2, or -A3 (+); (2) HLA-DR1, -DR4, -DR11, -DR13, or -DR15 (+); (3) ANC > 1000/mm(3); (4) Platelets >100,000/mm(3); (5) Hgb > 9 g/dL; (6) HGBA1C < 7%; (7) Hepatic: a) AST and ALT </= 2.5 x upper limits of normal (ULN) b) Bilirubin </= 2.5 x ULN c) Alkaline phosphatase </= 2.5 x ULN; (8) Renal a) Creatinine </= 1.5 x ULN; (9) Serology (within 6 months of study entry) a) HIV negative b) Hepatitis C negative; (10) LDH up to 1.5 x ULN.

11) Age 18 years or older at randomization.

12) Participants must have at least two intact (undissected) axillary and/or inguinal lymph node basins.

Exclusion Criteria:

1) Participants with ocular melanoma.

2) Participants who received the following medications or treatments any time within 4 wks of randomization: 1) Chem; 2) Interferon (e.g. Intron-AŽ); 3) Radiation (Stereotactic radiotherapy, such as gamma knife, can be used greater than or equal to 1 week and less than or equal to 6 months prior to randomization) 4) Allergy desensitization

3) Participants who received the following medications or treatments any time within 4 wks of randomization: 5) Corticosteroids, administered transdermally parenterally, or orally. Inhaled steroids (e.g.: AdvairŽ, FloventŽ, AzmacortŽ) are not permitted. Topical corticosteroids are acceptable; 6) Growth factors (e.g. ProcritŽ, AranespŽ, NeulastaŽ); 7) Interleukins (e.g. ProleukinŽ); 8) Any investigational medication.

4) Participants who are currently receiving nitrosoureas or who have received this therapy within the preceding 6 weeks.

5) Participants with known or suspected allergies to any component of the vaccine.

6) Participants may not have been vaccinated previously with any of the synthetic peptides included in this protocol.

7) Participants who have received vaccinations containing agents other than the synthetic peptides included in this protocol and have recurred during or after administration of the vaccine will be eligible to enroll 12 weeks following their last vaccination.

8) Pregnancy. Female participants of childbearing potential must have a negative pregnancy test (urinary or serum beta-HCG) obtained within 2 weeks prior to randomization. Males and females must agree, in the consent form, to use effective birth control methods during the course of vaccination.

9) Female participants must not be breastfeeding.

10) Participants in whom there is a medical contraindication or potential problem in complying with the requirements of the protocol in the opinion of the investigator.

11) Participants classified according to the New York Heart Association classification as having Class III or IV heart disease.

12) Participants with uncontrolled diabetes, defined as having a HGBA1C >/= 7%.

13) 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; 1) The presence of laboratory evidence of autoimmune disease (e.g. positive ANA titer) without symptoms; 2) Clinical evidence of vitiligo; 3) Other forms of depigmenting illness; 4) Mild arthritis requiring NSAID medications.

14) Participants who have another cancer diagnosis, except that the following diagnoses will be allowed: 1) squamous cell cancer of the skin without known metastasis; 2) basal cell cancer of the skin without known metastasis; 3) carcinoma in situ of the breast (DCIS or LCIS); 4) carcinoma in situ of the cervix; 5) any cancer without distant metastasis that has been treated successfully, without evidence of recurrence or metastasis for over 5 years.

15) Participants with known addiction to alcohol or drugs who are actively taking those agents, or participants with recent (within 1 year) or ongoing illicit IV drug use.

16) Body weight < 110 pounds (without clothes) at randomization, due to the amount and frequency with which blood will be drawn.

Links

Registration Number: NCT00118274
Study Information on Clinical Trials Registry (clinicaltrials.gov)