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Vaccine Therapy in Treating Patients With Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

Primary Purpose

Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
NY-ESO-1 peptide 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 stage II ovarian epithelial cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, primary peritoneal cavity cancer, fallopian tube 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-IV at diagnosis, receiving initial cytoreductive surgery and chemotherapy with at least one platinum-based chemotherapy regimen. High risk feature defined as suboptimal primary debulking (remaining tumor masses with diameter ≥ 1.0 cm) or failure to normalize CA125 during primary therapy by the end of the third cycle or positive second-look surgery. Patients must be in complete clinical remission defined as CA125 < 35 units, negative physical examination and no definite evidence of disease by computed tomography (CT) of the abdomen and pelvis. Lymph nodes and/or soft tissue abnormalities ≤ 1.0 cm that are often present in the pelvis may not be considered definite evidence of disease. Expected survival of at least 6 months. Karnofsky performance scale ≥60%. Within the last 2 weeks prior to study day 1, vital laboratory parameters should be within normal range, except for the following laboratory parameters, which should be within the ranges specified: Absolute neutrophil count (ANC) ≥1000/mm^3 Platelets ≥ 80,000/mm^3 Creatinine ≤ 1.5mg/dL Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), and total bilirubin all < 2.5 x upper limit of normal (ULN) 7 Age ≥ 18 years. 8. Able and willing to give valid written informed consent. 9. HLA A02 positive. Exclusion Criteria Patients were excluded from the study for any of the following reasons: Clinically significant heart disease (NYHA Class III or IV). Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders. Patients with serious intercurrent illness, requiring hospitalization. Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available. Patients taking immunosuppressive drugs such as systemic corticosteroids or non-steroidal anti-inflammatory drugs. Known HIV positivity. Other malignancy within 3 years prior to entry into the study, except for treated nonmelanoma skin cancer and cervical carcinoma in situ. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study. Lack of availability for immunological and clinical follow-up assessments. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment. Pregnancy or breastfeeding. Women of childbearing potential: Refusal or inability to use effective means of contraception.

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

NY-ESO-1b peptide with Montanide® ISA-51

Arm Description

Patients received NY-ESO-1b peptide mixed with Montanide® ISA-51 by subcutaneous injections, once every 3 weeks (weeks 1, 4, 7, 10, and 13) for a total of 13 weeks.

Outcomes

Primary Outcome Measures

Number of Patients With Dose Limiting Toxicities (DLTs)
Toxicities and adverse events defined by National Cancer Institute Common Toxicity Criteria (CTC) Scale (Version 2.0, published April 30, 1999). DLT defined as: ≥ Grade 2 autoimmune phenomena, asymptomatic bronchospasm or generalized urticaria, or ≥ Grade 3 hematological and non hematological toxicities. To be dose-limiting, an adverse event must be definitely, probably, or possibly related to the administration of the investigational agent.

Secondary Outcome Measures

Number of Patients Developing NY-ESO-1 Antibodies After Treatment
Blood samples were obtained at baseline and in weeks 4, 7, 10, 13 and 16 for the assessment of NY-ESO-1 specific antibodies by enzyme-linked immunosorbent assay (ELISA).
Number of Patients With NY-ESO-1b-Specific CD8+ T Cells Measured by Tetramer Analysis
Blood samples were obtained at baseline and at 4, 7, 10. 13 and 16 weeks. Tetramer assays were conducted after presensitization of CD8+ T cells with NY-ESO-1b. Results are presented separately for patients with NY-ESO-1 positive and negative tumors.
Number of Patients With NY-ESO-1b-Specific Activated CD8+ T Cells Measured by ELISPOT
Blood samples were obtained at baseline and at 4, 7, 10, 13 and 16 weeks. T cell responses were monitored after the in vitro sensitization with NY-ESO-1b (157-165), modified NY-ESO-1b-A (157-165A), or control peptide influenza matrix 58 to 66. Results are presented separately for patients with NY-ESO-1 positive and negative tumors.
Number of Patients With NY-ESO-1b-specific Delayed-type Hypersensitivity (DTH)
NY-ESO-1b-specific delayed-type hypersensitivity (DTH) was measured by number of patients with induration and/or redness at each timepoint. NY-ESO-1b-specific DTH skin reaction was measured at baseline and weeks 7 and 16. The NY-ESO-1b peptide solution (0.1 mg/mL in 8% DMSO) was injected intradermally at a separate site from the vaccination to give a visable and palpable skin depot. The extent and intensity of DTH reactions were documented by measuring visible redness, palpable induration and other signs of local skin irritation or necrosis. Assessment of DTH reaction was performed 48 hours after injection, and the diameter of the reaction was documented.

Full Information

First Posted
August 6, 2003
Last Updated
October 2, 2023
Sponsor
Ludwig Institute for Cancer Research
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00066729
Brief Title
Vaccine Therapy in Treating Patients With Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer
Official Title
A Phase I Study Of NY-ESO-1b Peptide Plus Montanide ® ISA-51 In Patients With Ovarian, Primary Peritoneal, Or Fallopian Tube Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
June 23, 2003 (Actual)
Primary Completion Date
May 9, 2006 (Actual)
Study Completion Date
August 1, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ludwig Institute for Cancer Research
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. PURPOSE: A phase I trial to study the side effects of vaccine therapy in patients with ovarian epithelial, primary peritoneal, or fallopian tube cancer.
Detailed Description
OBJECTIVES: Determine the safety of NY-ESO-1b peptide vaccine and Montanide® ISA-51 in patients with ovarian epithelial, primary peritoneal, or fallopian tube cancer. Determine the immunologic profile (NY-ESO-1 antibody, CD8+ cells, and delayed-type hypersensitivity) induced by this regimen in these patients. OUTLINE: This is an open-label study. Patients receive NY-ESO-1b peptide vaccine emulsified with Montanide® ISA-51 subcutaneously once every 3 weeks on weeks 1, 4, 7, 10, and 13 in the absence of disease progression or unacceptable toxicity. Patients are followed at 3 weeks (week 16) and then every 6-12 weeks for 2 years or until disease progression.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NY-ESO-1b peptide with Montanide® ISA-51
Arm Type
Experimental
Arm Description
Patients received NY-ESO-1b peptide mixed with Montanide® ISA-51 by subcutaneous injections, once every 3 weeks (weeks 1, 4, 7, 10, and 13) for a total of 13 weeks.
Intervention Type
Biological
Intervention Name(s)
NY-ESO-1 peptide vaccine
Intervention Description
NY-ESO-1b peptide 100 μg mixed with 0.5 mL of Montanide® ISA-51
Primary Outcome Measure Information:
Title
Number of Patients With Dose Limiting Toxicities (DLTs)
Description
Toxicities and adverse events defined by National Cancer Institute Common Toxicity Criteria (CTC) Scale (Version 2.0, published April 30, 1999). DLT defined as: ≥ Grade 2 autoimmune phenomena, asymptomatic bronchospasm or generalized urticaria, or ≥ Grade 3 hematological and non hematological toxicities. To be dose-limiting, an adverse event must be definitely, probably, or possibly related to the administration of the investigational agent.
Time Frame
up to 16 weeks
Secondary Outcome Measure Information:
Title
Number of Patients Developing NY-ESO-1 Antibodies After Treatment
Description
Blood samples were obtained at baseline and in weeks 4, 7, 10, 13 and 16 for the assessment of NY-ESO-1 specific antibodies by enzyme-linked immunosorbent assay (ELISA).
Time Frame
up to 16 weeks
Title
Number of Patients With NY-ESO-1b-Specific CD8+ T Cells Measured by Tetramer Analysis
Description
Blood samples were obtained at baseline and at 4, 7, 10. 13 and 16 weeks. Tetramer assays were conducted after presensitization of CD8+ T cells with NY-ESO-1b. Results are presented separately for patients with NY-ESO-1 positive and negative tumors.
Time Frame
up to 16 weeks.
Title
Number of Patients With NY-ESO-1b-Specific Activated CD8+ T Cells Measured by ELISPOT
Description
Blood samples were obtained at baseline and at 4, 7, 10, 13 and 16 weeks. T cell responses were monitored after the in vitro sensitization with NY-ESO-1b (157-165), modified NY-ESO-1b-A (157-165A), or control peptide influenza matrix 58 to 66. Results are presented separately for patients with NY-ESO-1 positive and negative tumors.
Time Frame
up to 16 weeks
Title
Number of Patients With NY-ESO-1b-specific Delayed-type Hypersensitivity (DTH)
Description
NY-ESO-1b-specific delayed-type hypersensitivity (DTH) was measured by number of patients with induration and/or redness at each timepoint. NY-ESO-1b-specific DTH skin reaction was measured at baseline and weeks 7 and 16. The NY-ESO-1b peptide solution (0.1 mg/mL in 8% DMSO) was injected intradermally at a separate site from the vaccination to give a visable and palpable skin depot. The extent and intensity of DTH reactions were documented by measuring visible redness, palpable induration and other signs of local skin irritation or necrosis. Assessment of DTH reaction was performed 48 hours after injection, and the diameter of the reaction was documented.
Time Frame
up to 16 weeks

10. Eligibility

Sex
Female
Gender Based
Yes
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-IV at diagnosis, receiving initial cytoreductive surgery and chemotherapy with at least one platinum-based chemotherapy regimen. High risk feature defined as suboptimal primary debulking (remaining tumor masses with diameter ≥ 1.0 cm) or failure to normalize CA125 during primary therapy by the end of the third cycle or positive second-look surgery. Patients must be in complete clinical remission defined as CA125 < 35 units, negative physical examination and no definite evidence of disease by computed tomography (CT) of the abdomen and pelvis. Lymph nodes and/or soft tissue abnormalities ≤ 1.0 cm that are often present in the pelvis may not be considered definite evidence of disease. Expected survival of at least 6 months. Karnofsky performance scale ≥60%. Within the last 2 weeks prior to study day 1, vital laboratory parameters should be within normal range, except for the following laboratory parameters, which should be within the ranges specified: Absolute neutrophil count (ANC) ≥1000/mm^3 Platelets ≥ 80,000/mm^3 Creatinine ≤ 1.5mg/dL Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), and total bilirubin all < 2.5 x upper limit of normal (ULN) 7 Age ≥ 18 years. 8. Able and willing to give valid written informed consent. 9. HLA A02 positive. Exclusion Criteria Patients were excluded from the study for any of the following reasons: Clinically significant heart disease (NYHA Class III or IV). Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders. Patients with serious intercurrent illness, requiring hospitalization. Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available. Patients taking immunosuppressive drugs such as systemic corticosteroids or non-steroidal anti-inflammatory drugs. Known HIV positivity. Other malignancy within 3 years prior to entry into the study, except for treated nonmelanoma skin cancer and cervical carcinoma in situ. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study. Lack of availability for immunological and clinical follow-up assessments. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment. Pregnancy or breastfeeding. Women of childbearing potential: Refusal or inability to use effective means of contraception.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jakob Dupont, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
18451240
Citation
Diefenbach CS, Gnjatic S, Sabbatini P, Aghajanian C, Hensley ML, Spriggs DR, Iasonos A, Lee H, Dupont B, Pezzulli S, Jungbluth AA, Old LJ, Dupont J. Safety and immunogenicity study of NY-ESO-1b peptide and montanide ISA-51 vaccination of patients with epithelial ovarian cancer in high-risk first remission. Clin Cancer Res. 2008 May 1;14(9):2740-8. doi: 10.1158/1078-0432.CCR-07-4619.
Results Reference
result

Learn more about this trial

Vaccine Therapy in Treating Patients With Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

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