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

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ClinicalTrials.gov Identifier: NCT00112957
Recruitment Status : Completed
First Posted : June 3, 2005
Results First Posted : March 19, 2018
Last Update Posted : March 19, 2018
Sponsor:
Collaborator:
Roswell Park Cancer Institute
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research

Tracking Information
First Submitted Date  ICMJE June 2, 2005
First Posted Date  ICMJE June 3, 2005
Results First Submitted Date  ICMJE February 13, 2018
Results First Posted Date  ICMJE March 19, 2018
Last Update Posted Date March 19, 2018
Actual Study Start Date  ICMJE December 2004
Actual Primary Completion Date May 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 15, 2018)
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00112957 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2018)
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vaccine Therapy in Patients With Stage II, III, or IV Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer
Official Title  ICMJE 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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Fallopian Tube Cancer
  • Ovarian Cancer
  • Peritoneal Cavity Cancer
Intervention  ICMJE
  • 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.
Study Arms  ICMJE 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.
Interventions:
  • Biological: rV-NY-ESO-1 vaccine
  • Biological: rF-NY-ESO-1 vaccine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 15, 2018)
23
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE May 2009
Actual Primary Completion Date May 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00112957
Other Study ID Numbers  ICMJE LUD 2002-012
RPCI-I-13303
CDR0000424461
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Ludwig Institute for Cancer Research
Study Sponsor  ICMJE Ludwig Institute for Cancer Research
Collaborators  ICMJE Roswell Park Cancer Institute
Investigators  ICMJE
Principal Investigator: Kunle Odunsi, MD, PhD Roswell Park Cancer Institute
PRS Account Ludwig Institute for Cancer Research
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP