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Vaccine Therapy in Patients With Stage II, III, or IV Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00112957
Recruitment Status : Completed
First Posted : June 3, 2005
Results First Posted : March 19, 2018
Last Update Posted : March 19, 2018
Roswell Park Cancer Institute
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research

Brief Summary:
This was a Phase 2, single-center, open-label study of recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1) and recombinant fowlpox-NY-ESO-1 (rF-NY-ESO-1) injections in patients who had a complete response to standard therapy for epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and whose tumors expressed NY-ESO-1 or LAGE-1 antigen. Study objectives were to evaluate maintenance of remission at 12 months, time to failure of vaccine therapy, cellular and humoral immunity and any correlation with time to failure, and safety.

Condition or disease Intervention/treatment Phase
Fallopian Tube Cancer Ovarian Cancer Peritoneal Cavity Cancer Biological: rV-NY-ESO-1 vaccine Biological: rF-NY-ESO-1 vaccine Phase 2

Detailed Description:
Patients received a single intradermal injection of rV-NY-ESO-1 (3.1 × 10^7 plaque forming units [PFU]) on Day 1, followed by monthly subcutaneous injections of rF-NY-ESO-1 (7.41 × 10^7 PFU) for 6 months (Days 29, 57, 85, 113, 141, and 169) or until observation of treatment-related ≥ grade 3 toxicity or disease progression. Study injections were administered during a 28-week evaluation period. Patients returned to the clinic for follow-up on Day 197 (i.e., 28 days after the last study injection) and every 2 months thereafter for at least 12 months. In patients with measurable disease, tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Patients were monitored continuously for safety for the duration of study participation.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Recombinant Vaccinia-NY-ESO-1 (rV-NY-ESO-1) and Recombinant Fowlpox-NY-ESO-1 (rF-NY-ESO-1) in Patients With Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma Whose Tumors Express NY-ESO-1 or LAGE-1 Antigen
Actual Study Start Date : December 2004
Actual Primary Completion Date : May 2009
Actual Study Completion Date : May 2009

Arm Intervention/treatment
Experimental: rV- and rF-NY-ESO-1
Patients received a single intradermal injection of rV-NY-ESO-1 (3.1 × 10^7 PFU) on Day 1, followed by subcutaneous injections of rF-NY-ESO-1 (7.41 × 10^7 PFU) on Days 29, 57, 85, 113, 141, and 169 or until observation of treatment-related ≥ grade 3 toxicity or disease progression.
Biological: rV-NY-ESO-1 vaccine
Patients received a single intradermal injection of rV-NY-ESO-1 (3.1 × 10^7 PFU) on Day 1.

Biological: rF-NY-ESO-1 vaccine
Patients received subcutaneous injections of rF-NY-ESO-1 (7.41 × 10^7 PFU) on Days 29, 57, 85, 113, 141, and 169.

Primary Outcome Measures :
  1. Percentage of Patients in Remission at 1 Year [ Time Frame: 12 months ]
    Time to failure (TTF) was evaluated as the crude proportion of patients in remission at 1 year, calculated as: 100 x (number of patients in remission at 1 year)/(number of patients with known status at 1 year). The Kaplan-Meier cumulative estimate of the proportion of patients in remission at 1 year was also calculated.

Secondary Outcome Measures :
  1. Mean Time to Failure Among Patients Who Progressed On Study [ Time Frame: Up to 20 months ]
    TTF was calculated as the number of days from the first dose until the patient discontinued due to progressive disease. Patients who completed the study or discontinued for other reasons were considered censored at the day of their last study visit, including the follow-up visits after Day 197. Progression was defined using the Response Evaluation Criteria In Solid Tumors (RECIST [version 1.0]) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  2. Number of Patients With Best Overall Tumor Response [ Time Frame: Up to 20 months ]
    Tumor responses were evaluated using computed tomography and were categorized according to RECIST (version 1.0) at Screening, on Days 85 and 197 and every 2 months thereafter for at least 12 months. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions (no evaluable disease); Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.

  3. Mean Absolute Cancer Antigen-125 Values Over Time on Study [ Time Frame: Up to 20 months ]
    Blood samples were collected to measure serum levels of tumor marker cancer antigen (CA)-125 at Screening and on Days 1, 29, 57, 85, 113, 141, 169, and 197 and every 2 months for at least 12 months following Day 197.

  4. Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity [ Time Frame: Up to 20 months ]
    Specific antibody response to the NY-ESO-1 and LAGE-1 antigen was measured by enzyme-linked immunosorbent assay (ELISA) at Screening, Days 29, 57, 85, 113, 141, 169, 197, Month 6, and Month 12.

  5. Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens [ Time Frame: Up to 20 months ]
    Intracellular cytokine staining assays were performed at Screening, Days 85 and 197, Month 6, and Month 12 to evaluate the release of interferon-gamma by CD4 and CD8 T cells following study injections.

  6. Number of Patients With Detectable T-cell Responses Following Vaccination [ Time Frame: Up to 20 months ]
    NY-ESO-1-specific CD8+ T cells (human leukocyte antigen [HLA]-A2 patients only) and NY-ESO-1-specific CD4+ T cells (HLA-DP4 patients only) were measured by interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) assay. The response to the ELISPOT assay was considered to be positive if the number of spots in the peptide-exposed well was 2-fold or more higher than the number of spots in the unstimulated well, and if there was a minimum of 10 (after subtraction of background spots) peptide-specific spots/25,000 T-cells, or less if T-cell clones were used.

  7. Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination [ Time Frame: Up to 6 months ]
    NY-ESO-1 antigen-specific delayed-type hypersensitivity (DTH) was measured by skin test at Screening and on Days 113 and 197. All patients were tested for the NY-ESO-1 protein, with additional DTH testing as follows: patients who were HLA-A2+ had NY-ESO-1b testing, patients who were HLA-DP4+ had NY-ESO-DP4 testing, and patients who were both HLA-A2+ and HLA-DP4+ had NY-ESO-1b and NY-ESO-DP4 testing.

  8. Number of Patients With Treatment-emergent Adverse Events [ Time Frame: Continuously for up to 20 months ]
    Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 3.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically documented epithelial carcinoma arising in the ovary, fallopian tube, or peritoneum, from stage II to IV at diagnosis.
  2. Received initial surgery and chemotherapy with at least one platinum-based chemotherapy regimen.
  3. Demonstrated complete response to first line therapy as evidenced by negative clinical examination, cancer antigen (CA)-125 tumor marker, and computed tomography (CT) scan. In addition, if second-look surgery was performed, patients must have had no evidence of microscopic or macroscopic disease. Patients must have been within 6 months of completing their first line platinum-based chemotherapy. These patients would normally enter a period of observation as standard management.
  4. Tumor expression of 1) NY-ESO-1 by reverse transcription-polymerase chain reaction (RT-PCR) analysis, preferably, or immunohistochemistry; or 2) LAGE-1 by RT-PCR.
  5. Expected survival of at least 6 months.
  6. Full recovery from surgery.
  7. Karnofsky performance status of 70% or more.
  8. Patients must have had the following clinical laboratory results:

    • neutrophil count: ≥ 1.5 x 10^9/L
    • lymphocyte count: ≥ 0.5 x 10^9/L
    • platelet count: ≥ 100 x 10^9/L
    • serum creatinine: ≤ 2 mg/dL
    • serum bilirubin: ≤ 2 mg/dL
  9. Ability to avoid close contact with children < 3 years of age; pregnant or breast feeding women; individuals with active, or a history of, eczema or atopic dermatitis or other skin disorders such as burns, chickenpox, shingles, impetigo, herpes, severe acne, or psoriasis; and immunocompromised individuals (human immunodeficiency virus [HIV], leukemia, lymphoma, solid organ transplantation, generalized malignancy, cellular or humoral immunodeficiency syndromes, patients currently receiving cytotoxic chemotherapies, radiation, or high dose corticosteroids).
  10. Have been informed of other treatment options.
  11. Age ≥ 18 years.
  12. Able and willing to give valid written informed consent.

Exclusion Criteria:

  1. Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may have been available.
  2. Other serious illnesses (eg, serious infections requiring antibiotics, bleeding disorders).
  3. History of current eczema or atopic dermatitis.
  4. History of autoimmune disease (eg., thyroiditis, lupus).
  5. Other acute, chronic, or exfoliative skin conditions such as burns, chickenpox, shingles, impetigo, herpes, severe acne, or psoriasis.
  6. Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs. Specific cyclooxygenase-2 inhibitors were permitted.
  7. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).
  8. Known HIV positivity.
  9. Known allergy or severe reaction to a smallpox (vaccinia) vaccination.
  10. Known allergy to eggs, determined by history.
  11. 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.
  12. Presence of 3 or more of the following risk factors:

    • Hypertension
    • Hypercholesterolemia
    • Diabetes
    • A first degree relative (for example, mother, father, brother, sister) who had a heart condition before the age of 50
    • Current cigarette smoker
  13. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
  14. Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
  15. Lack of availability of a patient for immunological and clinical follow-up assessment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00112957

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United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Ludwig Institute for Cancer Research
Roswell Park Cancer Institute
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Principal Investigator: Kunle Odunsi, MD, PhD Roswell Park Cancer Institute

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Responsible Party: Ludwig Institute for Cancer Research Identifier: NCT00112957     History of Changes
Other Study ID Numbers: LUD 2002-012
First Posted: June 3, 2005    Key Record Dates
Results First Posted: March 19, 2018
Last Update Posted: March 19, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Ludwig Institute for Cancer Research:
fallopian tube cancer
stage II ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
peritoneal cavity cancer
Additional relevant MeSH terms:
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Fallopian Tube Neoplasms
Neoplasms by Site
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Fallopian Tube Diseases
Immunologic Factors
Physiological Effects of Drugs