Decitabine, Vaccine Therapy, and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer

Brief Title

Decitabine, Vaccine Therapy, and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer

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

Brief Summary

      This phase I trial is studying the side effects and best dose of decitabine when given
      together with pegylated liposomal doxorubicin hydrochloride and vaccine therapy in treating
      patients with recurrent ovarian epithelial cancer, fallopian tube cancer, or peritoneal
      cancer. Drugs used in chemotherapy, such as decitabine and pegylated liposomal doxorubicin
      hydrochloride, 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 or antigen may help
      the body build an effective immune response to kill tumor cells. Giving combination
      chemotherapy together with vaccine therapy may kill more tumor cells

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the safety of 5-aza-2'-deoxycytidine (decitabine) in combination with
immunization with NYESO-I protein mixed with montanide and granulocyte-macrophage colony
stimulating factor (GM-CSF) in patients scheduled to receive liposomal doxorubicin for
recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma.

SECONDARY OBJECTIVES:

I. To evaluate NY-ESO-l specific cellular and humoral immunity by determination of NY-ESO-I
specific antibody, CD8+ and CD4+ T-cells following immunization with NY-ESO-l protein mixed
with montanide and GM-CSF in combination with 5-aza-2' -deoxycytidine (decitabine) in
patients receiving liposomal doxorubicin for recurrent epithelial ovarian, fallopian tube or
primary peritoneal carcinoma.

II. To determine the impact of 5-aza-2'-deoxycytidine on NY-ESO-I specific expression,
NY-ESO-l promoter methylation, and global DNA methylation.

III. To compare the time to progression (ttp) for the proposed therapy with the ttp for
standard therapy (historical studies).

OUTLINE: This is a dose escalation study of decitabine.

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

After completion of study treatment, patients are followed up at 6 months.

Study Phase

Phase 1

Study Type

Interventional

Primary Outcome

Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0

Secondary Outcome

 NY-ESO-1 specific cellular and humoral immunity as assessed by NY-ESO-1-specific CD8+ and CD4+ T cells and antibodies and frequency of CD4+ CD25+ FOXP3+ regulatory T cells

Condition

Recurrent Fallopian Tube Cancer

Intervention

decitabine

Study Arms / Comparison Groups

 Treatment (chemotherapy and vaccine therapy)

Description:  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 in incomplete Freund's adjuvant and sargramostim subcutaneously on day 15. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

April 2009

Completion Date

June 2013

Primary Completion Date

October 2011

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects with relapsed epithelial ovarian cancer (including fallopian tube and primary
             peritoneal cancer) who will receive liposomal doxorubicin as salvage therapy for
             recurrent disease

          -  Patients may have received up to four previous lines of chemotherapy

          -  The relapse may be defined by an increase in CA125; there may or may not be either
             measurable or symptomatic disease

          -  Any human leukocyte antigen (HLA) type

          -  No requirement for tumor expression of NY-ESO-1

          -  Karnofsky performance status of > 70%

          -  Not previously treated with doxorubicin

          -  Life expectancy >= 6 months

          -  Hematology and biochemistry laboratory results within the limits normally expected for
             the patient population, without evidence of major organ failure

          -  No immunodeficiency

          -  Have been informed of other treatment options

          -  Able and willing to give valid written informed consent

          -  Neutrophil count >= 1.5 x 10^9

          -  Platelet count >= 100 x 10^9

          -  Serum creatinine =< 2.1 mg/dL

          -  Serum bilirubin =< 2 mg/dL

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.6 x upper limit
             of normal (ULN) (normal ranges: AST 15-46 U/L; ALT 11-66 U/L)

        Exclusion Criteria:

          -  Metastatic disease to the central nervous system for which other therapeutic options,
             including radiotherapy, may be available

          -  Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding
             disorders)

          -  History of autoimmune disease (e.g., thyroiditis, lupus) except vitiligo

          -  Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal
             anti-inflammatory drugs; specific CQX-2 inhibitors are permitted

          -  Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing
             of study agent (6 weeks for nitrosoureas)

          -  Known human immunodeficiency virus (HIV) positivity

          -  Known allergy or history of life threatening reaction to GM-CSF

          -  Myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or
             transient ischemic attack, chest pain or shortness of breath with activity, or other
             heart conditions being treated by a doctor

          -  Participation in any other clinical trial involving another investigational agent
             within 4 weeks prior to first dosing of study agent

          -  Mental impairment that may compromise the ability to give informed consent and comply
             with the requirements of the study

          -  Lack of availability of a patient for immunological and clinical follow-up assessment

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Kunle Odunsi, ,

Location Countries

United States

Location Countries

United States

Administrative Informations

NCT ID

NCT01673217

Organization ID

I 127008

Secondary IDs

NCI-2010-00105

Responsible Party

Sponsor

Study Sponsor

Roswell Park Cancer Institute

Collaborators

 Eisai Inc.

Study Sponsor

Kunle Odunsi, Principal Investigator, Roswell Park Cancer Institute

Verification Date

July 2022