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

NCT01673217 | Completed Phase 1

• 2 other identifiers: I 127008NCI-2010-00105
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

Conditions

Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer

Outcome Measures

Primary Outcomes (1)

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

  Estimated with a one-sided, 95%, Wilson score binomial confidence interval.

  Up to 6 months

Secondary Outcomes (5)

• 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

• 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

• 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

Study Arms (1)

Treatment (chemotherapy and vaccine therapy)

EXPERIMENTAL

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.

Drug: decitabine; Biological: NY-ESO-1 peptide vaccine; Drug: pegylated liposomal doxorubicin hydrochloride; Biological: sargramostim; Biological: incomplete Freund's adjuvant; Other: immunohistochemistry staining method; Other: liquid chromatography; Other: mass spectrometry; Genetic: reverse transcriptase-polymerase chain reaction; Other: laboratory biomarker analysis; Genetic: DNA methylation analysis; Other: enzyme-linked immunosorbent assay

Interventions

decitabine DRUG

Given IV

Also known as: 5-aza-dCyd, 5AZA, DAC

Treatment (chemotherapy and vaccine therapy)

NY-ESO-1 peptide vaccine BIOLOGICAL

Given SC

Also known as: ESO-1 Peptide Vaccine

Treatment (chemotherapy and vaccine therapy)

pegylated liposomal doxorubicin hydrochloride DRUG

Given IV

Also known as: CAELYX, Dox-SL, DOXIL, doxorubicin hydrochloride liposome, LipoDox

Treatment (chemotherapy and vaccine therapy)

sargramostim BIOLOGICAL

Given SC

Also known as: GM-CSF, Leukine, Prokine

Treatment (chemotherapy and vaccine therapy)

incomplete Freund's adjuvant BIOLOGICAL

Given SC

Also known as: IFA, ISA-51, Montanide ISA 51

Treatment (chemotherapy and vaccine therapy)

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Treatment (chemotherapy and vaccine therapy)

liquid chromatography OTHER

Correlative studies

Also known as: LC

Treatment (chemotherapy and vaccine therapy)

mass spectrometry OTHER

Correlative studies

Treatment (chemotherapy and vaccine therapy)

reverse transcriptase-polymerase chain reaction GENETIC

Correlative studies

Also known as: RT-PCR

Treatment (chemotherapy and vaccine therapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (chemotherapy and vaccine therapy)

DNA methylation analysis GENETIC

Correlative studies

Treatment (chemotherapy and vaccine therapy)

enzyme-linked immunosorbent assay OTHER

Correlative studies

Also known as: ELISA

Treatment (chemotherapy and vaccine therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Eisai Inc.: collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

Decitabine; liposomal doxorubicin; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; incomplete Freund's adjuvant; montanide ISA 51; Immunohistochemistry; Chromatography, Liquid; Mass Spectrometry; Reverse Transcriptase Polymerase Chain Reaction; DNA Methylation; Enzyme-Linked Immunosorbent Assay

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; Chromatography; Chemistry Techniques, Analytical; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; Genetic Techniques; Methylation; Alkylation; Biochemical Phenomena; Chemical Phenomena; Metabolism; Genetic Phenomena; Immunoenzyme Techniques; Immunoassay; Immunosorbent Techniques; Molecular Probe Techniques

Study Officials

• Kunle Odunsi

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2012
• First Posted: August 27, 2012
• Study Start: April 1, 2009
• Primary Completion: October 1, 2011
• Study Completion: June 1, 2013
• Last Updated: August 1, 2022

Record last verified: 2022-07

Locations

US (1)