search
Back to results

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

Primary Purpose

Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rV-NY-ESO-1 vaccine
rF-NY-ESO-1 vaccine
Sponsored by
Ludwig Institute for Cancer Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fallopian Tube Cancer focused on measuring fallopian tube cancer, stage II ovarian epithelial cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, peritoneal cavity cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Histologically documented epithelial carcinoma arising in the ovary, fallopian tube, or peritoneum, from stage II to IV at diagnosis. Received initial surgery and chemotherapy with at least one platinum-based chemotherapy regimen. 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. 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. Expected survival of at least 6 months. Full recovery from surgery. Karnofsky performance status of 70% or more. 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 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). Have been informed of other treatment options. Age ≥ 18 years. Able and willing to give valid written informed consent. Exclusion Criteria: Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may have been available. Other serious illnesses (eg, serious infections requiring antibiotics, bleeding disorders). History of current eczema or atopic dermatitis. History of autoimmune disease (eg., thyroiditis, lupus). Other acute, chronic, or exfoliative skin conditions such as burns, chickenpox, shingles, impetigo, herpes, severe acne, or psoriasis. Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs. Specific cyclooxygenase-2 inhibitors were permitted. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas). Known HIV positivity. Known allergy or severe reaction to a smallpox (vaccinia) vaccination. Known allergy to eggs, determined by history. 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. 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 Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment. Mental impairment that may have compromised 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.

Sites / Locations

  • Roswell Park Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

rV- and rF-NY-ESO-1

Arm Description

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.

Outcomes

Primary Outcome Measures

Percentage of Patients in Remission at 1 Year
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

Mean Time to Failure Among Patients Who Progressed On Study
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
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
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
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
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
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
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
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.

Full Information

First Posted
June 2, 2005
Last Updated
October 2, 2023
Sponsor
Ludwig Institute for Cancer Research
Collaborators
Roswell Park Cancer Institute
search

1. Study Identification

Unique Protocol Identification Number
NCT00112957
Brief Title
Vaccine Therapy in Patients With Stage II, III, or IV Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
December 2004 (Actual)
Primary Completion Date
May 2009 (Actual)
Study Completion Date
May 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ludwig Institute for Cancer Research
Collaborators
Roswell Park Cancer Institute

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer
Keywords
fallopian tube cancer, stage II ovarian epithelial cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, peritoneal cavity cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
rV- and rF-NY-ESO-1
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
rV-NY-ESO-1 vaccine
Intervention Description
Patients received a single intradermal injection of rV-NY-ESO-1 (3.1 × 10^7 PFU) on Day 1.
Intervention Type
Biological
Intervention Name(s)
rF-NY-ESO-1 vaccine
Intervention Description
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 Measure Information:
Title
Percentage of Patients in Remission at 1 Year
Description
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.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Mean Time to Failure Among Patients Who Progressed On Study
Description
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
Time Frame
Up to 20 months
Title
Number of Patients With Best Overall Tumor Response
Description
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.
Time Frame
Up to 20 months
Title
Mean Absolute Cancer Antigen-125 Values Over Time on Study
Description
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.
Time Frame
Up to 20 months
Title
Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity
Description
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.
Time Frame
Up to 20 months
Title
Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens
Description
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.
Time Frame
Up to 20 months
Title
Number of Patients With Detectable T-cell Responses Following Vaccination
Description
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.
Time Frame
Up to 20 months
Title
Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination
Description
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.
Time Frame
Up to 6 months
Title
Number of Patients With Treatment-emergent Adverse Events
Description
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.
Time Frame
Continuously for up to 20 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically documented epithelial carcinoma arising in the ovary, fallopian tube, or peritoneum, from stage II to IV at diagnosis. Received initial surgery and chemotherapy with at least one platinum-based chemotherapy regimen. 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. 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. Expected survival of at least 6 months. Full recovery from surgery. Karnofsky performance status of 70% or more. 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 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). Have been informed of other treatment options. Age ≥ 18 years. Able and willing to give valid written informed consent. Exclusion Criteria: Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may have been available. Other serious illnesses (eg, serious infections requiring antibiotics, bleeding disorders). History of current eczema or atopic dermatitis. History of autoimmune disease (eg., thyroiditis, lupus). Other acute, chronic, or exfoliative skin conditions such as burns, chickenpox, shingles, impetigo, herpes, severe acne, or psoriasis. Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs. Specific cyclooxygenase-2 inhibitors were permitted. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas). Known HIV positivity. Known allergy or severe reaction to a smallpox (vaccinia) vaccination. Known allergy to eggs, determined by history. 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. 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 Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment. Mental impairment that may have compromised 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kunle Odunsi, MD, PhD
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

We'll reach out to this number within 24 hrs