Vaccine Therapy in Stage II, III, or IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancers

NCT ID: NCT00803569

Last Updated: 2023-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-14
• Study Completion Date: 2011-01-24

Brief Summary

This was a Phase 1, non-randomized, open-label, multicenter study of the ALVAC(2)-NY-ESO-1(M)/TRICOM vaccine administered with the granulocyte macrophage-colony stimulating factor (GM-CSF) sargramostim in patients with NY-ESO-1- or LAGE-1-positive epithelial ovarian, fallopian tube, or primary peritoneal cavity cancers who had completed standard therapy for primary or recurrent disease and would have normally entered a period of observation. The primary study objective was to determine the safety and tolerability of study vaccination, with secondary objectives including the determination of clinical and immunological responses.

Detailed Description

Patients received subcutaneous (SC) injections with 0.5 mL of ALVAC(2)-NY-ESO-1(M)/TRICOM on Day 1 and 100 μg of the GM-CSF sargramostim on Days 1 through 4 in continuous 28-day cycles for up to 6 cycles. No dose escalation of either vaccine component was permitted. Patients received study vaccinations until disease progression or unacceptable toxicity.

Safety was evaluated by continuous monitoring of adverse events (AEs), concomitant medications, and vital signs, as well as through hematology and chemistry laboratory testing and physical examinations. Efficacy was determined through tumor response evaluations, cancer antigen (CA)-125 levels, and cellular and humoral immune responses (i.e., NY-ESO-1-specific T cells, antibodies to NY-ESO-1 and ALVAC, and delayed-type hypersensitivity [DTH] testing).

Conditions

Fallopian Tube Cancer; Ovarian Cancer; Peritoneal Cavity Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ALVAC(2)-NY-ESO-1(M)/TRICOM + GM-CSF

Patients received SC injections with ALVAC(2)-NY-ESO-1(M)/TRICOM (0.5 mL) on Day 1 and the GM-CSF sargramostim (100 μg) on Days 1 through 4 in continuous 28-day cycles for up to 6 cycles.

Group Type: EXPERIMENTAL

ALVAC(2)-NY-ESO-1(M)/TRICOM vaccine

Intervention Type: BIOLOGICAL

The vaccine comprises the modified canary pox vector, ALVAC(2), inserted with the following genes: NYESO-1(M), TRICOM (LFA-3, ICAM-1, B7.1), vvE3L, vvK3L. The vaccine is administered at a dose of 0.5 mL SC.

Sargramostim

Intervention Type: BIOLOGICAL

The GM-CSF sargramostim is administered at a dose of 100 μg SC.

Interventions

ALVAC(2)-NY-ESO-1(M)/TRICOM vaccine

The vaccine comprises the modified canary pox vector, ALVAC(2), inserted with the following genes: NYESO-1(M), TRICOM (LFA-3, ICAM-1, B7.1), vvE3L, vvK3L. The vaccine is administered at a dose of 0.5 mL SC.

Intervention Type: BIOLOGICAL

Sargramostim

The GM-CSF sargramostim is administered at a dose of 100 μg SC.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Histologically documented epithelial carcinoma arising in the ovary, fallopian tube or peritoneum, from stage II-IV at diagnosis, treated with initial surgery and chemotherapy with at least one platinum-based chemotherapy regimen.

2. Complete response to frontline therapy as evidenced by negative clinical examination, CA-125 tumor marker, and computed tomography (CT) scan. In addition, if second look surgery was performed (by laparoscopy or laparotomy), the result must have been either negative or microscopic positive. These patients would have normally entered a period of observation after standard management.

3. Patients with recurrent disease were eligible if they had completed surgery and/or chemotherapy for recurrent disease and would have normally entered a period of observation after completion of standard management. Eligible patients could have had asymptomatic residual measurable disease on physical examination and/or CT scan, and/or could have had an elevated CA-125 or could have been in complete clinical remission (defined as a serum CA-125 ≤ 35 IU/mL, CT scan without objective evidence of disease, and normal physical examination).

4. Tumor expression of 1) NY-ESO-1 by reverse transcription-polymerase chain reaction (RT-PCR) (preferably) or immunohistochemistry (IHC); or 2) LAGE-1 by RT-PCR. Patients whose primary surgery was performed outside the study site were pre-screened and required to release tissue sections or blocks to the study site in order to determine tumor expression of NY-ESO-1 by IHC.

5. Expected survival of at least 6 months.

6. Full recovery from surgery.

7. Karnofsky performance status of 70 or more.

8. Laboratory parameters for vital functions were required to be in the normal range. Laboratory abnormalities that were not clinically significant were generally permitted, except for the following laboratory parameters, which were required to be within the ranges specified:

• neutrophil count: ≥ 1.5 × 10^9/L
• lymphocyte count: ≥ 0.5 × 10^9/L
• platelet count: ≥ 100 × 10^9/L
• serum creatinine: ≤ 2 mg/dL
• serum bilirubin (total): ≤ 2 mg/dL
• hemoglobin: ≥ 10 g/dL

9. Have been informed of other treatment options.

10. Age ≥ 18 years.

11. Able and willing to give valid written informed consent.

Exclusion Criteria

1. Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may have been available.

2. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).

3. History of autoimmune disease (e.g., thyroiditis, lupus) except vitiligo.

4. Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.

5. Known immunodeficiency or human immunodeficiency virus positivity.

6. Known allergy or history of life-threatening reaction to GM-CSF.

7. Known allergies to eggs, neomycin, and bovine products, determined by history.

8. History of severe allergic reactions to vaccines or unknown allergens.

9. Myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, chest pain or shortness of breath with activity, or other heart conditions being treated by a doctor.

10. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing of study agent.

11. Mental impairment that could have compromised the ability to give informed consent and comply with the requirements of the study.

12. Lack of availability for immunological and clinical follow-up assessment.

13. Previous NY-ESO-1 vaccine therapy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Roswell Park Cancer Institute

OTHER

Sponsor Role: collaborator

New York University Cancer Institute

OTHER

Sponsor Role: collaborator

Ludwig Institute for Cancer Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kunle Odunsi, MD, PhD

Role: STUDY_CHAIR

Roswell Park Cancer Institute

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

NYU Cancer Institute at New York University Medical Center

New York, New York, United States

Countries

United States

References

Withers HG, Matsuzaki J, Long M, Rosario SR, Chodon T, Tsuji T, Koya R, Yan L, Wang J, Keler T, Lele SB, Zsiros E, Lugade A, Hutson A, Blank S, Bhardwaj N, Shrikant P, Liu S, Odunsi K. mTOR inhibition modulates vaccine-induced immune responses to generate memory T cells in patients with solid tumors. J Immunother Cancer. 2025 Mar 25;13(3):e010408. doi: 10.1136/jitc-2024-010408.

Reference Type: DERIVED

PMID: 40132910 (View on PubMed)

Other Identifiers

CDR0000628730

Identifier Type: OTHER

Identifier Source: secondary_id

LUD2007-005

Identifier Type: -

Identifier Source: org_study_id