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Phase 1 Study of NY-ESO-1 Overlapping Peptides in Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

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ClinicalTrials.gov Identifier: NCT00616941
Recruitment Status : Completed
First Posted : February 15, 2008
Results First Posted : July 27, 2018
Last Update Posted : July 27, 2018
Sponsor:
Collaborator:
Memorial Sloan Kettering Cancer Center
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research

Tracking Information
First Submitted Date  ICMJE February 4, 2008
First Posted Date  ICMJE February 15, 2008
Results First Submitted Date  ICMJE April 28, 2017
Results First Posted Date  ICMJE July 27, 2018
Last Update Posted Date July 27, 2018
Actual Study Start Date  ICMJE March 2008
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2017)
Overview of Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Continuously for up to 16 weeks ]
Analysis of TEAEs reported from clinical laboratory tests, physical examinations, and vital signs from pre-treatment through 3 weeks after the last dose of study treatment.
Original Primary Outcome Measures  ICMJE
 (submitted: February 14, 2008)
To assess the safety of repeated vaccination with NY-ESO-1 overlapping peptides (4) (OLP4) with or without the adjuvant Montanide to patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. [ Time Frame: 16 weeks ]
Change History Complete list of historical versions of study NCT00616941 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2017)
  • Number of Patients With Detectable Serum Immunoglobulin G (IgG) Antibody Titers Against NY-ESO-1 Up to 16 Weeks Post-Baseline [ Time Frame: Screening and Weeks 4, 7, 10, 13, and 16 ]
    Blood samples were drawn to measure immunologic response at Screening and Weeks 4, 7, 10, 13, and 16. Specific antibodies against NY-ESO-1 were measured by enzyme-linked immunosorbent assay (ELISA).
  • Number of Patients With Detectable CD8+ and CD4+ T-cell Responses Up to 16 Weeks Post-Baseline [ Time Frame: Screening and Weeks 4, 7, 10, 13, and 16 ]
    Blood samples were drawn to measure immunologic response at Screening and Weeks 4, 7, 10, 13, and 16. NY-ESO-1-specific CD8+ and CD4+ T-cell reactivity was measured by tetramer analysis (in human leukocyte antigen [HLA] 0201* patients). Interferon gamma (IFN-γ) release by T cells was measured by the enzyme-linked immunospot (ELISPOT) assay. A subject was considered to have experienced a T-cell response if IFN-γ spots were detectable (>50 spots) by ELISPOT of 50,000 CD8+ and CD4+ T cells following pre-sensitization with a pool of 20-mer OLP covering all of NY-ESO-1 and tested against Epstein-Barr virus-transformed B cells pulsed with 3 subpools of these peptides.
  • Number of Patients With Delayed-type Hypersensitivity (DTH) Reactions (Induration and Redness) to NY-ESO-1 OLP4 at Screening and Week 16 [ Time Frame: Screening and Week 16 ]
    NY-ESO-1-specific DTH was measured by skin tests at Screening and again at Week 16. NY-ESO-1 OLP4 (40 µg in 0.1 mL D5W) was injected intradermally, with DTH reactions read 48 hours after injection.
  • Cancer Antigen (CA)-125 Levels Up to 16 Weeks Post-Baseline [ Time Frame: Screening, Week 7, and Week 16 ]
    Serum CA-125 was measured at Screening, Week 7, and Week 16. Stable CA-125 at baseline was < 35 U/mL (defined as CA-125 that had not doubled from the post chemotherapy nadir).
  • Tumor Measurement Results According to the Response Evaluation Criteria for Solid Tumors (RECIST) Up to 16 Weeks Post-Baseline [ Time Frame: Screening and every 2 months up to Week 16 ]
    Radiographic imaging (computed tomography of the abdomen and pelvis) was obtained at Screening and every 2 months during the study, and at unscheduled time points if any clinical symptoms/examination findings warranted further evaluation or if serum CA-125 rose to > 70 U/mL (confirmed by repeat value). Subjects may have had more than 1 location of disease.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2008)
To evaluate the immune response (NY-ESO-1 antibody, CD4+ and CD8+ cells) induced by NY-ESO-1 OLP4 vaccine with or without Montanide. [ Time Frame: 16 Weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1 Study of NY-ESO-1 Overlapping Peptides in Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Official Title  ICMJE A Phase 1 Study of NY-ESO-1 Overlapping Peptides With or Without Immunoadjuvants Montanide and Poly-ICLC Vaccination of Epithelial Ovarian Cancer, Fallopian Tube, or Primary Peritoneal Cancer Patients in Second or Third Remission
Brief Summary This was a Phase 1, open-label study of repeated vaccination with NY-ESO-1 overlapping peptides (OLP4) with or without the immunoadjuvants Montanide and polyinosinic-polycytidylic acid - poly-L-lysine carboxymethylcellulose (poly-ICLC) administered every 3 weeks for a total of 5 vaccinations in subjects with epithelial ovarian, fallopian tube, or primary peritoneal cancer in second or third clinical remission. Study objectives included determination of the safety and immunogenicity following vaccination.
Detailed Description

Subjects received NY-ESO-1 OLP4 by subcutaneous injection once every 3 weeks (Weeks 1, 4, 7, 10, and 13) for a total of 5 vaccinations.

Subjects were assigned sequentially to 1 of 3 dosing cohorts:

Cohort 1: received NY-ESO-1 OLP4 alone; Cohort 2: received NY-ESO-1 OLP4 in combination with Montanide; Cohort 3: received NY-ESO-1 OLP4 in combination with Montanide and Poly-ICLC.

Enrollment into each subsequent dosing cohort was dependent on a dose-limiting toxicity (DLT) rate of <33% in the preceding cohort. No dose escalation was planned.

Subjects were observed by study staff for up to 30 minutes following each vaccination. Immunologic assessments were performed prior to the first vaccination and 3 weeks after each vaccination. Toxicity assessments were performed with each vaccination and 3 weeks after the completion of therapy (ie, the final study visit was Week 16). Immunologic assessments included measurement of the anti-NY-ESO-1 antibody by enzyme-linked immunsorbent assay (ELISA), detection of CD-4 and CD-8 cellular responses by tetramer and enzyme-linked immunosorbent spot assay (ELISPOT), and delayed-type hypersensitivity (DTH).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Epithelial Ovarian Cancer
  • Fallopian Tube Cancer
  • Primary Peritoneal Cancer
Intervention  ICMJE
  • Biological: NY-ESO-1 OLP4
    1.0 mg of NY-ESO-1 OLP4 (0.25 mg of each overlapping peptide) was diluted in 0.5 mL of 5% dextrose in water (D5W) and administered subcutaneously as a single injection.
  • Biological: NY-ESO-1 OLP4 + Montanide
    1.0 mg of NY-ESO-1 OLP4 (0.25 mg of each overlapping peptide) was diluted in 0.5 mL of D5W, mixed with 0.5 mL of Montanide, and administered subcutaneously as a single injection.
  • Biological: NY-ESO-1 OLP4 + Montanide + Poly-ICLC
    1.0 mg of NY-ESO-1 OLP4 (0.25 mg of each overlapping peptide) and 1.4 mg of poly-ICLC were emulsified in 1.0 mL of Montanide and administered subcutaneously as two injections.
Study Arms  ICMJE
  • Experimental: Cohort 1
    Subjects received 4 synthetic peptides coded by the NY-ESO-1 gene (ie, NY-ESO-1 OLP4) once every 3 weeks for a total of 5 vaccinations.
    Intervention: Biological: NY-ESO-1 OLP4
  • Experimental: Cohort 2
    Subjects received 4 synthetic peptides coded by the NY-ESO-1 gene (ie, NY-ESO-1 OLP4) in combination with Montanide ISA-51 vegetable grade (VG) once every 3 weeks for a total of 5 vaccinations.
    Intervention: Biological: NY-ESO-1 OLP4 + Montanide
  • Experimental: Cohort 3
    Subjects received 4 synthetic peptides coded by the NY-ESO-1 gene (ie, NY-ESO-1 OLP4) in combination with Montanide ISA-51 VG and poly-ICLC once every 3 weeks for a total of 5 vaccinations.
    Intervention: Biological: NY-ESO-1 OLP4 + Montanide + Poly-ICLC
Publications *

*   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: October 19, 2017)
28
Original Estimated Enrollment  ICMJE
 (submitted: February 14, 2008)
15
Actual Study Completion Date  ICMJE June 2011
Actual Primary Completion Date June 2011   (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, stage II to IV at diagnosis, and post-initial cytoreductive surgery and chemotherapy with at least one platinum-based chemotherapy regimen.
  2. In second or third stable complete clinical remission, defined as a) stable cancer antigen (CA)-125 < 35 U/ml (defined as CA-125 that had not doubled from the post chemotherapy nadir), b) unremarkable physical examination, and c) 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 were not considered definite evidence of disease.
  3. Expected survival of at least 4 months.
  4. Karnofsky performance scale ≥ 70%.
  5. Laboratory values within the following limits:

    • Hemoglobin ≥ 10.0 g/dL
    • Neutrophil count ≥ 1.5 x 10^9/L
    • Platelet count ≥ 80 x 10^9/L
    • Serum creatinine ≤ 2.0 mg/dL
    • Serum bilirubin ≤ 2.5 x institutional upper limit of normal (ULN)
    • aspartate aminotransferase/alanine aminotransferase ≤ 2.5 x institutional ULN
  6. Age ≥ 18 years.
  7. ≥ 4 weeks since completion of prior cytotoxic chemotherapy.
  8. Able and willing to give valid written informed consent

Exclusion Criteria:

  1. Clinically significant heart disease (New York Heart Association Class III or IV).
  2. Serious intercurrent illness, eg, serious infections requiring prolonged parenteral antibiotics or bleeding disorders requiring hospitalization.
  3. Positive stool guaiac excluding hemorrhoids.
  4. Known autoimmune disease (ie, rheumatoid arthritis, ulcerative colitis, etc); or immune deficiency (human immunodeficiency virus, hypogammaglobulinemia); or known active infections with Hepatitis B or Hepatitis C; or receipt of immunosuppressive drugs such as systemic corticosteroids or cyclosporin, etc.
  5. Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
  6. History of previous severe allergic reactions to vaccines or unknown allergens.
  7. Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
  8. Lack of availability for immunological and clinical follow-up assessments.
  9. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent.
  10. Pregnancy or breast-feeding.
  11. Women of childbearing potential: Refusal or inability to use effective means of contraception.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Subjects must have had selected female reproductive organ cancers.
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 NCT00616941
Other Study ID Numbers  ICMJE LUD2006-001
MSKCC IRB# 07-152
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Data have been published
Responsible Party Ludwig Institute for Cancer Research
Study Sponsor  ICMJE Ludwig Institute for Cancer Research
Collaborators  ICMJE Memorial Sloan Kettering Cancer Center
Investigators  ICMJE
Principal Investigator: Paul Sabbatini, MD Memorial Sloan Kettering Cancer Center
PRS Account Ludwig Institute for Cancer Research
Verification Date October 2017

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