Clinical trial NCT00616941: Phase 1 Study of NY-ESO-1 Overlapping Peptides in Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Epithelial Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
Keywords: NY-ESO-1 OLP4
Ovarian Cancer
Cancer Vaccine
Lead sponsor: Ludwig Institute for Cancer Research
Sponsor class: OTHER
Collaborators: name: Memorial Sloan Kettering Cancer Center
First posted: 2008-02-15
Enrollment: 28
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

Eligibility 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.

Primary outcomes:
measure: Overview of Treatment-emergent Adverse Events (TEAEs)
timeFrame: Continuously for up to 16 weeks
Secondary outcomes:
measure: Number of Patients With Detectable Serum Immunoglobulin G (IgG) Antibody Titers Against NY-ESO-1 Up to 16 Weeks Post-Baseline
timeFrame: Screening and Weeks 4, 7, 10, 13, and 16
measure: Number of Patients With Detectable CD8+ and CD4+ T-cell Responses Up to 16 Weeks Post-Baseline
timeFrame: Screening and Weeks 4, 7, 10, 13, and 16
measure: Number of Patients With Delayed-type Hypersensitivity (DTH) Reactions (Induration and Redness) to NY-ESO-1 OLP4 at Screening and Week 16
timeFrame: Screening and Week 16
measure: Cancer Antigen (CA)-125 Levels Up to 16 Weeks Post-Baseline
timeFrame: Screening, Week 7, and Week 16
measure: Tumor Measurement Results According to the Response Evaluation Criteria for Solid Tumors (RECIST) Up to 16 Weeks Post-Baseline
timeFrame: Screening and every 2 months up to Week 16
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Paul Sabbatini, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sabbatini P, Tsuji T, Ferran L, Ritter E, Sedrak C, Tuballes K, Jungbluth AA, Ritter G, Aghajanian C, Bell-McGuinn K, Hensley ML, Konner J, Tew W, Spriggs DR, Hoffman EW, Venhaus R, Pan L, Salazar AM, Diefenbach CM, Old LJ, Gnjatic S. Phase I trial of overlapping long peptides from a tumor self-antigen and poly-ICLC shows rapid induction of integrated immune response in ovarian cancer patients. Clin Cancer Res. 2012 Dec 1;18(23):6497-508. doi: 10.1158/1078-0432.CCR-12-2189. Epub 2012 Oct 2.
citation: Tsuji T, Sabbatini P, Jungbluth AA, Ritter E, Pan L, Ritter G, Ferran L, Spriggs D, Salazar AM, Gnjatic S. Effect of Montanide and poly-ICLC adjuvant on human self/tumor antigen-specific CD4+ T cells in phase I overlapping long peptide vaccine trial. Cancer Immunol Res. 2013 Nov;1(5):340-50. doi: 10.1158/2326-6066.CIR-13-0089. Epub 2013 Sep 16.