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Vaccine Therapy With or Without Cyclophosphamide in Treating Patients Who Have Undergone Surgery for Stage II, Stage III, or Stage IV Melanoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2008 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00118274
First received: July 8, 2005
Last updated: February 6, 2009
Last verified: November 2008
  Purpose

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cyclophosphamide may also stimulate the immune system in different ways and stop tumor cells from growing. Giving vaccine therapy together with cyclophosphamide after surgery may cause a stronger immune response to kill any remaining tumor cells. It may also prevent or delay the recurrence of melanoma.

PURPOSE: This randomized phase I/II trial is studying the side effects of vaccine therapy when given with or without cyclophosphamide and to see how well they work in treating patients who have undergone surgery for stage II, stage III, or stage IV melanoma.


Condition Intervention Phase
Melanoma (Skin)
Biological: incomplete Freund's adjuvant
Biological: melanoma helper peptide vaccine
Biological: multi-epitope melanoma peptide vaccine
Biological: tetanus toxoid helper peptide
Drug: cyclophosphamide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety if less than 33% of patients experience a dose-limiting toxicity up to week 52 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immunogenicity by Elispot assay up to week 52 [ Designated as safety issue: No ]

Estimated Enrollment: 173
Study Start Date: March 2005
Estimated Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive vaccine comprising multi-epitope melanoma peptides, tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
Biological: incomplete Freund's adjuvant
Given intradermally and subcutaneously
Biological: multi-epitope melanoma peptide vaccine
Given intradermally and subcutaneously
Biological: tetanus toxoid helper peptide
Given intradermally and subcutaneously
Experimental: Arm II
Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine comprising multi-epitope melanoma peptides, tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
Biological: incomplete Freund's adjuvant
Given intradermally and subcutaneously
Biological: multi-epitope melanoma peptide vaccine
Given intradermally and subcutaneously
Biological: tetanus toxoid helper peptide
Given intradermally and subcutaneously
Drug: cyclophosphamide
Given IV
Experimental: Arm III
Patients receive vaccine comprising melanoma peptides and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
Biological: incomplete Freund's adjuvant
Given intradermally and subcutaneously
Biological: melanoma helper peptide vaccine
Given intradermally and subcutaneously
Biological: multi-epitope melanoma peptide vaccine
Given intradermally and subcutaneously
Experimental: Arm IV
Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine comprising melanoma peptides and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
Biological: incomplete Freund's adjuvant
Given intradermally and subcutaneously
Biological: melanoma helper peptide vaccine
Given intradermally and subcutaneously
Biological: multi-epitope melanoma peptide vaccine
Given intradermally and subcutaneously
Drug: cyclophosphamide
Given IV

Detailed Description:

OBJECTIVES:

Primary

  • Determine the safety of adjuvant vaccine therapy comprising multi-epitope melanoma peptides (MP) and multi-epitope melanoma helper peptides (MHP) emulsified in Montanide ISA-51 in patients with resected stage IIB-IV melanoma.
  • Determine the safety of administering cyclophosphamide before vaccination in these patients.
  • Compare the magnitude of immune response against vaccination comprising MP in combination with either MHP or tetanus toxoid helper peptide (TET) emulsified in Montanide ISA-51 with vs without cyclophosphamide in these patients.

Secondary

  • Compare the response rate and persistence of immune responses in patients treated with these regimens.
  • Compare the magnitude of immune response against vaccination comprising TET or MHP with vs without cyclophosphamide in these patients.
  • Compare the response rate and persistence of immune response against vaccination comprising TET or MHP with vs without cyclophosphamide in these patients.
  • Determine the delayed-type hypersensitivity response to the peptide components of these vaccines in these patients.
  • Compare, preliminarily, disease-free survival of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to HLA-type (HLA-A1 positive vs HLA-A2 positive, HLA-A1 negative, or -A3 negative vs HLA-A3 positive, or -A1 negative) and participating center (University of Virginia [UVA] vs non-UVA). Patients are randomized to 1 of 4 treatment arms.

  • Arm I: Patients receive vaccine comprising multi-epitope melanoma peptides (MP) and tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally (ID) and subcutaneously (SC) on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
  • Arm II: Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine as in arm I.
  • Arm III: Patients receive vaccine comprising MP and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 ID and SC on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
  • Arm IV: Patients receive cyclophosphamide as in arm II. Patients then receive vaccine as in arm III.

Treatment in all arms continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 173 patients will be accrued for this study within 2 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed melanoma

    • Cutaneous, mucosal, or primary melanoma
    • Stage IIB-IV disease
  • Has undergone surgical resection or stereotactic radiosurgery for malignant melanoma ≥ 1 week but ≤ 6 months ago

    • No clinical or radiological evidence of disease after surgical resection or stereotactic radiosurgery by chest x-ray or CT scan*, abdominal and pelvic CT scan*, and head CT scan or MRI NOTE: *Positron emission tomography scan/CT fusion scan may replace scans of the chest, abdomen, and pelvis
  • Must have ≥ 2 intact (undissected) axillary and/or inguinal lymph node basins
  • HLA-A1, -A2, or -A3 positive AND HLA-DR1, -DR4, -DR11, -DR13, or -DR15 positive
  • Ineligible for OR refused interferon
  • No ocular melanoma
  • Brain metastases allowed provided all of the following criteria are met:

    • No more than 3 total brain metastases
    • Each metastasis ≤ 2 cm in diameter at the time of study entry
    • Each metastasis was completely removed by surgery or treated with stereotactic radiosurgery
    • No evidence of brain metastasis progression since the most recent treatment

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count > 1,000/mm^3
  • Platelet count > 100,000/mm^3
  • Hemoglobin > 9 g/dL

Hepatic

  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 2.5 times ULN
  • Lactic dehydrogenase ≤ 1.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Hepatitis C negative

Renal

  • Creatinine ≤ 1.5 times ULN

Cardiovascular

  • No New York Heart Association class III or IV heart disease

Immunologic

  • HIV negative
  • No known or suspected allergy to any component of the study vaccines
  • No autoimmune disorder with visceral involvement
  • No prior or active autoimmune disorder requiring cytotoxic or immunosuppressive therapy
  • The following immunologic conditions are allowed:

    • Laboratory evidence of autoimmune disease (e.g., positive anti-nuclear antibody titer) without symptoms
    • Clinical evidence of vitiligo
    • Other forms of depigmenting illness
    • Mild arthritis requiring non-steroidal anti-inflammatory drugs

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Weight ≥ 110 lbs
  • No uncontrolled diabetes

    • Hemoglobin A1C < 7%
  • No medical contraindication or potential problem that would preclude study compliance
  • No other malignancy except squamous cell or basal cell skin cancer without known metastasis, carcinoma in situ of the breast (ductal or lobular) or cervix, or other successfully treated cancer without distant metastasis with no evidence of recurrence or metastasis for > 5 years
  • No known active addiction to alcohol or drugs
  • No recent (within the past year) or ongoing illicit IV drug use

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior vaccination with any of the synthetic peptides used in this study

    • Prior vaccinations (containing agents other than the synthetic peptides used in this study) that resulted in recurrent disease during or after vaccine administration allowed provided the last vaccination was administered more than 12 weeks ago
  • More than 4 weeks since prior and no concurrent interferon (e.g., Intron-A®), interleukins (e.g., Proleukin®), or growth factors (e.g., Procrit®, Aranesp®, or Neulasta®)
  • More than 4 weeks since prior and no concurrent allergy desensitization injections
  • No influenza vaccines for at least 2 weeks before or after study vaccine administration

Chemotherapy

  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
  • No concurrent chemotherapy, including nitrosoureas

Endocrine therapy

  • More than 4 weeks since prior and no concurrent oral or parenteral corticosteroids
  • No prior or concurrent inhaled steroids (e.g., Advair®, Flovent®, or Azmacort®)
  • Prior or concurrent topical corticosteroids allowed

Radiotherapy

  • See Disease Characteristics
  • More than 4 weeks since other prior and no concurrent radiotherapy

Surgery

  • See Disease Characteristics

Other

  • More than 4 weeks since prior and no other concurrent investigational agents
  • More than 30 days since prior and no concurrent participation in another clinical study
  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: NCT00118274

Locations
United States, Pennsylvania
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, United States, 19111-2497
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
United States, Virginia
University of Virginia Cancer Center
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Craig L. Slingluff, MD University of Virginia
  More Information

Additional Information:
No publications provided

Responsible Party: Craig L. Slingluff, Jr, University of Virginia Cancer Center
ClinicalTrials.gov Identifier: NCT00118274     History of Changes
Other Study ID Numbers: CDR0000430929, UVACC-HIC-11491, UVACC-34104, UVACC-MEL-44, UVACC-GCRC-CLS013, UVACC-HITC-02620, MDA-2005-0070
Study First Received: July 8, 2005
Last Updated: February 6, 2009
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage II melanoma
stage III melanoma
stage IV melanoma

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Cyclophosphamide
Freund's Adjuvant
Adjuvants, Immunologic
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014