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

A Phase I Study Of NY-ESO-1b Peptide Plus Montanide ® ISA-51 In Patients With Ovarian, Primary Peritoneal, Or Fallopian Tube Cancer

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cavity Cancer
• Intervention / Treatment: Biological: NY-ESO-1 peptide vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. 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.
2. 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.
3. 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.
4. Expected survival of at least 6 months.
5. Karnofsky performance scale ≥60%.

6. 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:

1. Clinically significant heart disease (NYHA Class III or IV).
2. Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders.
3. Patients with serious intercurrent illness, requiring hospitalization.
4. Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available.
5. Patients taking immunosuppressive drugs such as systemic corticosteroids or non-steroidal anti-inflammatory drugs.
6. Known HIV positivity.
7. Other malignancy within 3 years prior to entry into the study, except for treated nonmelanoma skin cancer and cervical carcinoma in situ.
8. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
9. Lack of availability for immunological and clinical follow-up assessments.
10. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
11. Pregnancy or breastfeeding.
12. Women of childbearing potential: Refusal or inability to use effective means of contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NY-ESO-1b peptide with Montanide® ISA-51; 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.	Biological: NY-ESO-1 peptide vaccine; NY-ESO-1b peptide 100 μg mixed with 0.5 mL of Montanide® ISA-51

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	up to 16 weeks
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.	up to 16 weeks.
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.	up to 16 weeks
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.	up to 16 weeks

Collaborators and Investigators

• Sponsor: Ludwig Institute for Cancer Research
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Jakob Dupont, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2003
• Primary Completion (Actual): May 9, 2006
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: August 6, 2003
• First Submitted That Met QC Criteria: August 6, 2003
• First Posted (Estimated): August 7, 2003

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; fallopian tube cancer; primary peritoneal cavity cancer; stage II ovarian epithelial cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Adnexal Diseases; Fallopian Tube Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Fallopian Tube Neoplasms
• Other Study ID Numbers: CDR0000318803; MSKCC-03034 (Other Identifier: Memorial Sloan-Kettering Cancer Center); LUD2002-014 (Other Identifier: Ludwig Institute for Cancer Research)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No