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A Phase I Clinical Trial of NY-ESO-1 Protein Immunization in Combination With 5-AZA-2'-Deoxycytidine (Decitabine) in Patients Receiving Liposomal Doxorubicin for Recurrent Epithelial Ovarian or Primary Peritoneal Carcinoma


Phase 1
18 Years
N/A
Open (Enrolling)
Female
Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer

Thank you

Trial Information

A Phase I Clinical Trial of NY-ESO-1 Protein Immunization in Combination With 5-AZA-2'-Deoxycytidine (Decitabine) in Patients Receiving Liposomal Doxorubicin for Recurrent Epithelial Ovarian or Primary Peritoneal Carcinoma


OBJECTIVES:

Primary

- Determine the safety of decitabine when administered in combination with NY-ESO-1
peptide vaccine (emulsified with incomplete Freund's adjuvant and sargramostim
[GM-CSF]) and pegylated liposomal doxorubicin hydrochloride in patients with recurrent
ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.

Secondary

- Evaluate NY-ESO-1-specific cellular and humoral immunity by determination of
NY-ESO-1-specific antibodies and CD8+ and CD4+ T cells in patients treated with this
regimen.

- Determine the impact of decitabine on NY-ESO-1-specific expression, NY-ESO-1-promoter
methylation, and global DNA methylation.

- Compare the time to progression in patients treated with this regimen vs patients
treated with standard therapy (historical studies).

OUTLINE: This is a dose-escalation study of decitabine.

Patients receive decitabine IV over 3 hours on day 1, pegylated liposomal doxorubicin
hydrochloride IV on day 8, and NY-ESO-1 peptide vaccine emulsified with incomplete Freund's
adjuvant and sargramostim (GM-CSF) subcutaneously on day 15. Treatment repeats every 28 days
for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically to assess NY-ESO-1-specific cellular and humoral
immunity by measuring NY-ESO-1-specific antibodies by ELISA; NY-ESO-1-specific CD8+ and CD4+
T cells by IFNγ-release ELISPOT assays; and the frequency of CD4+ CD25+ FOXP3+ regulatory T
cells. Tumor tissue samples are collected periodically to assess NY-ESO-1 expression by
quantitative RT-PCR and IHC; NY-ESO-1 promoter DNA methylation by pyrosequencing; and global
genomic DNA methylation by liquid chromatography-mass spectrometry.

After completion of study therapy, patients are followed at 2 weeks and then at 6 months.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of recurrent ovarian epithelial cancer, fallopian tube cancer, or primary
peritoneal cancer

- Relapse may be defined by an increase in CA-125 (measurable or symptomatic
disease not required)

- Tumor expression of NY-ESO-1 is not required

- Any HLA type allowed

- Planning to receive pegylated liposomal doxorubicin hydrochloride as salvage therapy
for recurrent disease

- No CNS metastasis for which other therapeutic options (e.g., radiotherapy) may be
available

PATIENT CHARACTERISTICS:

- Karnofsky performance status of 80-100%

- Life expectancy ≥ 6 months

- Neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Serum creatinine ≤ 2.1 mg/dL

- Serum bilirubin ≤ 2 mg/dL

- AST or ALT ≤ 2.6 times upper limit of normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No immunodeficiency

- No known HIV positivity

- No known allergy or history of life-threatening reaction to sargramostim (GM-CSF)

- No other serious illness (e.g., serious infection requiring antibiotics or bleeding
disorder)

- No history of autoimmune disease (e.g., thyroiditis or lupus) except vitiligo

- No evidence of major organ failure

- No myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or
transient ischemic attack, chest pain or shortness of breath with activity, or other
heart condition currently being treated by a physician

- No mental impairment that may compromise the ability to give informed consent or
comply with study requirements

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas), radiotherapy,
or immunotherapy

- More than 4 weeks since prior participation in any other clinical trial involving
another investigational agent

- No more than 4 prior lines of chemotherapy

- No prior doxorubicin hydrochloride

- No concurrent systemic corticosteroids, antihistamines, nonsteroidal
anti-inflammatory drugs, or other immunosuppressive agents

- Concurrent specific COX-2 inhibitors allowed

- No other concurrent chemotherapy

- Concurrent non-cytotoxic anti-cancer therapy (e.g., hormonal therapy for breast
cancer or tamoxifen therapy for ovarian cancer) allowed

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toxicity as measured by NCI CTCAE v3.0 criteria

Outcome Time Frame:

Daily

Safety Issue:

Yes

Principal Investigator

Adekunle O. Odunsi, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000640517

NCT ID:

NCT00887796

Start Date:

April 2009

Completion Date:

Related Keywords:

  • Fallopian Tube Cancer
  • Ovarian Cancer
  • Peritoneal Cavity Cancer
  • recurrent ovarian epithelial cancer
  • fallopian tube cancer
  • peritoneal cavity cancer
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Glandular and Epithelial

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263