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

Primary Purpose

Epithelial Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

NY-ESO-1 OLP4

NY-ESO-1 OLP4 + Montanide

NY-ESO-1 OLP4 + Montanide + Poly-ICLC

About this trial

This is an interventional treatment trial for Epithelial Ovarian Cancer focused on measuring NY-ESO-1 OLP4, Ovarian Cancer, Cancer Vaccine

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, stage II to IV at diagnosis, and post-initial cytoreductive surgery and chemotherapy with at least one platinum-based chemotherapy regimen.
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.
Expected survival of at least 4 months.
Karnofsky performance scale ≥ 70%.
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
Age ≥ 18 years.
≥ 4 weeks since completion of prior cytotoxic chemotherapy.
Able and willing to give valid written informed consent

Exclusion Criteria:

Clinically significant heart disease (New York Heart Association Class III or IV).
Serious intercurrent illness, eg, serious infections requiring prolonged parenteral antibiotics or bleeding disorders requiring hospitalization.
Positive stool guaiac excluding hemorrhoids.
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.
Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
History of previous severe allergic reactions to vaccines or unknown allergens.
Mental impairment that may have compromised 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 first dose of study agent.
Pregnancy or breast-feeding.
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 2

Arm 3

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Overview of Treatment-emergent Adverse Events (TEAEs)

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

Number of Patients With Detectable Serum Immunoglobulin G (IgG) Antibody Titers Against NY-ESO-1 Up to 16 Weeks Post-Baseline

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

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

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

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

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.

Full Information

NCT ID

NCT00616941

First Posted

February 4, 2008

Last Updated

October 3, 2022

Sponsor

Ludwig Institute for Cancer Research

Collaborators

Memorial Sloan Kettering Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT00616941

Brief Title

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

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Completed

Study Start Date

March 2008 (Actual)

Primary Completion Date

June 2011 (Actual)

Study Completion Date

June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ludwig Institute for Cancer Research

Collaborators

Memorial Sloan Kettering Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epithelial Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer

Keywords

NY-ESO-1 OLP4, Ovarian Cancer, Cancer Vaccine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

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.

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

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.

Arm Title

Cohort 3

Arm Type

Experimental

Arm Description

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 Type

Biological

Intervention Name(s)

NY-ESO-1 OLP4

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

NY-ESO-1 OLP4 + Montanide

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

NY-ESO-1 OLP4 + Montanide + Poly-ICLC

Intervention Description

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 Measure Information:

Title

Overview of Treatment-emergent Adverse Events (TEAEs)

Description

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.

Time Frame

Continuously for up to 16 weeks

Secondary Outcome Measure Information:

Title

Number of Patients With Detectable Serum Immunoglobulin G (IgG) Antibody Titers Against NY-ESO-1 Up to 16 Weeks Post-Baseline

Description

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).

Time Frame

Screening and Weeks 4, 7, 10, 13, and 16

Title

Number of Patients With Detectable CD8+ and CD4+ T-cell Responses Up to 16 Weeks Post-Baseline

Description

Time Frame

Screening and Weeks 4, 7, 10, 13, and 16

Title

Number of Patients With Delayed-type Hypersensitivity (DTH) Reactions (Induration and Redness) to NY-ESO-1 OLP4 at Screening and Week 16

Description

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.

Time Frame

Screening and Week 16

Title

Cancer Antigen (CA)-125 Levels Up to 16 Weeks Post-Baseline

Description

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).

Time Frame

Screening, Week 7, and Week 16

Title

Tumor Measurement Results According to the Response Evaluation Criteria for Solid Tumors (RECIST) Up to 16 Weeks Post-Baseline

Description

Time Frame

Screening and every 2 months up to Week 16

10. Eligibility

Sex

Female

Gender Based

Yes

Gender Eligibility Description

Subjects must have had selected female reproductive organ cancers.

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 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. Expected survival of at least 4 months. Karnofsky performance scale ≥ 70%. 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 Age ≥ 18 years. ≥ 4 weeks since completion of prior cytotoxic chemotherapy. Able and willing to give valid written informed consent Exclusion Criteria: Clinically significant heart disease (New York Heart Association Class III or IV). Serious intercurrent illness, eg, serious infections requiring prolonged parenteral antibiotics or bleeding disorders requiring hospitalization. Positive stool guaiac excluding hemorrhoids. 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. Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ. History of previous severe allergic reactions to vaccines or unknown allergens. Mental impairment that may have compromised 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 first dose of study agent. Pregnancy or breast-feeding. Women of childbearing potential: Refusal or inability to use effective means of contraception.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Paul Sabbatini, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Principal Investigator

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

Yes

IPD Sharing Plan Description

Data have been published

Citations:

PubMed Identifier

23032745

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.

Results Reference

result

PubMed Identifier

24777970

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.

Results Reference

derived

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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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