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

Phase 1

Completed

• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cavity Cancer
• Interventions: Biological: ALVAC(2)-NY-ESO-1(M)/TRICOM vaccine; Biological: Sargramostim

• Registration Number: NCT00803569
• Lead Sponsor: Ludwig Institute for Cancer Research

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).

Study Timeline

• Study Start: 2008-11-14
• Study First Submitted: 2008-12-04
• Study First Submitted QC: 2008-12-04
• Study First Posted: 2008-12-05
• Primary Completion: 2011-01-24
• Study Completion: 2011-01-24
• Results First Submitted: 2018-01-03
• Results First Submitted QC: 2018-09-21
• Results First Posted: 2019-02-15
• Status Verified: 2022-10
• Last Update Submitted: 2023-10-02
• Last Update Posted: 2023-10-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 13

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ALVAC(2)-NY-ESO-1(M)/TRICOM + GM-CSF	ALVAC(2)-NY-ESO-1(M)/TRICOM vaccine	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.
ALVAC(2)-NY-ESO-1(M)/TRICOM + GM-CSF	Sargramostim	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.

Primary Outcome Measures

Name	Time	Method
Number of Patients With Treatment-emergent Adverse Events	Continuously for up to 26 weeks	Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period.

Secondary Outcome Measures

Name	Time	Method
Median Progression-free Survival (PFS)	Baseline and up to approximately 24 weeks	PFS was calculated from the date of the first dose of study drug to the date of documented progression or death, whichever occurred first. Patients without disease progression or death had their observation time censored at the date of the last valid disease assessment. PFS was summarized using Kaplan-Meier product-limit estimators.
Number of Patients With Best Overall Tumor Response	Baseline and Weeks 12 and 24	Tumor responses were evaluated using computed tomography and categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0) at baseline, at Week 12 (± 28 days), and at Week 24 (end of study). Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions \[no evidence of disease\]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
Median Cancer Antigen 25 (CA-125) Values on Study	Baseline through Week 24	Blood samples were collected for CA-125 testing as a component of disease evaluations at Baseline and Weeks 8, 12, 16, 20, and 24 (end of study) or every 2 to 3 months on study according to standard institutional practice.
Number of Patients With NY-ESO-1 and LAGE-1 Antigen Positivity	Baseline through Week 24	Blood samples were collected for measurement of NY-ESO-1 and LAGE-1 antigen positivity at Baseline and Weeks 4, 8 ,12, 16, 20, and 24 (end of study). Antibody testing was performed by enzyme-linked immunosorbent assay (ELISA).

Trial Locations

Locations (2)

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

NYU Cancer Institute at New York University Medical Center; 🇺🇸 New York, New York, United States