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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

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.

Condition or disease Intervention/treatment Phase
Epithelial Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer Biological: NY-ESO-1 OLP4 Biological: NY-ESO-1 OLP4 + Montanide Biological: NY-ESO-1 OLP4 + Montanide + Poly-ICLC Phase 1

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).


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 2008
Actual Primary Completion Date : June 2011
Actual Study Completion Date : June 2011


Arm Intervention/treatment
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.
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.

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.
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.

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.
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.

  4. 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).

  5. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Subjects must have had selected female reproductive organ cancers.
Accepts Healthy Volunteers:   No
Criteria

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.

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 ClinicalTrials.gov identifier (NCT number): NCT00616941


Locations
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United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Ludwig Institute for Cancer Research
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Paul Sabbatini, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier: NCT00616941     History of Changes
Other Study ID Numbers: LUD2006-001
MSKCC IRB# 07-152
First Posted: February 15, 2008    Key Record Dates
Results First Posted: July 27, 2018
Last Update Posted: July 27, 2018
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data have been published

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ludwig Institute for Cancer Research:
NY-ESO-1 OLP4
Ovarian Cancer
Cancer Vaccine
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Poly I-C
Carboxymethylcellulose Sodium
Vaccines
Poly ICLC
Immunologic Factors
Physiological Effects of Drugs
Interferon Inducers
Laxatives