Decitabine, Vaccine Therapy, and Doxorubicin Hydrochloride Liposome in Treating Patients With Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer - Full Text View

Sponsors and Collaborators:	Roswell Park Cancer Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00887796

Purpose

RATIONALE: Drugs used in chemotherapy, such as decitabine and doxorubicin hydrochloride liposome, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vaccines made from a peptide may help the body build an effective immune response to kill tumor cells. Giving chemotherapy together with vaccine therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of decitabine when given together with vaccine therapy and doxorubicin hydrochloride liposome in treating patients with recurrent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.

Condition	Intervention	Phase
Fallopian Tube Cancer Ovarian Cancer Peritoneal Cavity Cancer	Biological: NY-ESO-1 peptide vaccine Biological: incomplete Freund's adjuvant Biological: sargramostim Drug: decitabine Drug: pegylated liposomal doxorubicin hydrochloride Genetic: DNA methylation analysis Genetic: reverse transcriptase-polymerase chain reaction Other: enzyme-linked immunosorbent assay Other: immunoenzyme technique Other: immunohistochemistry staining method Other: laboratory biomarker analysis Other: liquid chromatography Other: mass spectrometry	Phase I

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Myocet Sargramostim 5-Aza-2'-deoxycytidine Freund's adjuvant

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	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

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

Primary Outcome Measures:

Toxicity as measured by NCI CTCAE v3.0 criteria [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

NY-ESO-1-specific cellular and humoral immunity as measured by NY-ESO-1-specific CD8+ and CD4+ T cells, NY-ESO-1-specific antibodies, and frequency of CD4+ CD25+ FOXP3+ regulatory T cells [ Designated as safety issue: No ]
NY-ESO-1 expression as measured by quantitative RT-PCR and IHC [ Designated as safety issue: No ]
Time to progression [ Designated as safety issue: No ]
NY-ESO-1 promoter DNA methylation as measured by pyrosequencing [ Designated as safety issue: No ]
Global genomic DNA methylation as measured by liquid chromatography-mass spectrometry and LINE-1 pyrosequencing [ Designated as safety issue: No ]

Estimated Enrollment:	18
Study Start Date:	April 2009
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the safety of decitabine when administered in combination with NY-ESO-1 peptide vaccine (emulsified with incomplete Freund's adjuvant and 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 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.

Eligibility

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

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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00887796

Locations

United States, New York
Roswell Park Cancer Institute	Recruiting
Buffalo, New York, United States, 14263-0001
Contact: Clinical Trials Office - Roswell Park Cancer Institute 877-275-7724

Sponsors and Collaborators

Roswell Park Cancer Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Adekunle O. Odunsi, MD, PhD

Roswell Park Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Roswell Park Cancer Institute ( Adekunle Omotayo Odunsi )
Study ID Numbers:	CDR0000640517, RPCI-I-127008
Study First Received:	April 23, 2009
Last Updated:	April 23, 2009
ClinicalTrials.gov Identifier:	NCT00887796 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent ovarian epithelial cancer
fallopian tube cancer
peritoneal cavity cancer

Study placed in the following topic categories:

Antimetabolites
Fallopian Tube Cancer
Immunologic Factors
Gonadal Disorders
Urogenital Neoplasms
Ovarian Diseases
Genital Diseases, Female
Anti-Bacterial Agents
Peritoneal Diseases
Ovarian Cancer
Endocrine Gland Neoplasms
Ovarian Neoplasms
Digestive System Neoplasms
Genital Neoplasms, Female
Adjuvants, Immunologic

Endocrine System Diseases
Decitabine
Abdominal Neoplasms
Ovarian Epithelial Cancer
Recurrence
Fallopian Tube Neoplasms
Doxorubicin
Carcinoma
Fallopian Tube Diseases
Digestive System Diseases
Gastrointestinal Neoplasms
Freund's Adjuvant
Peritoneal Neoplasms
Endocrinopathy

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Gonadal Disorders
Antineoplastic Agents
Physiological Effects of Drugs
Urogenital Neoplasms
Ovarian Diseases
Antibiotics, Antineoplastic
Genital Diseases, Female
Neoplasms by Site
Therapeutic Uses
Peritoneal Diseases
Endocrine Gland Neoplasms

Ovarian Neoplasms
Digestive System Neoplasms
Adjuvants, Immunologic
Genital Neoplasms, Female
Endocrine System Diseases
Enzyme Inhibitors
Decitabine
Abdominal Neoplasms
Fallopian Tube Neoplasms
Doxorubicin
Pharmacologic Actions
Adnexal Diseases
Fallopian Tube Diseases
Neoplasms
Digestive System Diseases

ClinicalTrials.gov processed this record on May 06, 2009