Decitabine, Vaccine Therapy, and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer
- Conditions
- Recurrent Fallopian Tube CancerRecurrent Ovarian Epithelial CancerRecurrent Primary Peritoneal Cavity Cancer
- Interventions
- Biological: NY-ESO-1 peptide vaccineBiological: sargramostimBiological: incomplete Freund's adjuvantOther: immunohistochemistry staining methodOther: liquid chromatographyOther: mass spectrometryGenetic: reverse transcriptase-polymerase chain reactionOther: laboratory biomarker analysisGenetic: DNA methylation analysisOther: enzyme-linked immunosorbent assay
- Registration Number
- NCT01673217
- Lead Sponsor
- Roswell Park Cancer Institute
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 18
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (chemotherapy and vaccine therapy) NY-ESO-1 peptide vaccine 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. Treatment (chemotherapy and vaccine therapy) pegylated liposomal doxorubicin hydrochloride 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. Treatment (chemotherapy and vaccine therapy) sargramostim 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. Treatment (chemotherapy and vaccine therapy) mass spectrometry 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. Treatment (chemotherapy and vaccine therapy) enzyme-linked immunosorbent assay 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. Treatment (chemotherapy and vaccine therapy) reverse transcriptase-polymerase chain reaction 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. Treatment (chemotherapy and vaccine therapy) incomplete Freund's adjuvant 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. Treatment (chemotherapy and vaccine therapy) liquid chromatography 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. Treatment (chemotherapy and vaccine therapy) DNA methylation analysis 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. Treatment (chemotherapy and vaccine therapy) immunohistochemistry staining method 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. Treatment (chemotherapy and vaccine therapy) laboratory biomarker analysis 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. Treatment (chemotherapy and vaccine therapy) 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 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.
- Primary Outcome Measures
Name Time Method Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Up to 6 months Estimated with a one-sided, 95%, Wilson score binomial confidence interval.
- Secondary Outcome Measures
Name Time Method 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 Up to 6 months Will be summarized by quartiles. Also, confidence intervals will be constructed for the median and the mean.
NY-ESO-l expression using Q-RT-PCR and IHC Days 1, 8, 15, 36, 43, 64, 71, 92, and 99 Time to progression Up to 6 months Summarized by a Kaplan-Meier survival curve.
NY-ESO-l promoter DNA methylation using pyrosequencing Days 1, 8, 15, 36, 43, 64, 71, 92, and 99 Global genomic DNA methylation using liquid chromatography-mass spectrometry (LC-MS) and LINE-l pyrosequencing Days 1, 8, 15, 36, 43, 64, 71, 92, and 99
Trial Locations
- Locations (1)
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States