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

• Sponsor: Ludwig Institute for Cancer Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00803569
• Collaborator: Roswell Park Cancer Institute (Other), New York University Cancer Institute (Other)
• Enrollment: 13
• Locations: 2
• Arm: 1
• Actual Duration (Months): 26.3
• Patients Per Site: 6.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Cancer; Ovarian Cancer; Peritoneal Cavity Cancer	Biological: ALVAC(2)-NY-ESO-1(M)/TRICOM vaccine; Biological: Sargramostim	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: All patients received the same study treatment.All patients received the same study treatment.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Study of ALVAC(2)-NY-ESO-1(M)/TRICOM (VCP2292) in Patients With Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma Whose Tumors Express NY-ESO-1 or LAGE-1 Antigen
• Actual Study Start Date: Nov 14, 2008
• Actual Primary Completion Date: Jan 24, 2011
• Actual Study Completion Date: Jan 24, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: 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.; Biological: Sargramostim; The GM-CSF sargramostim is administered at a dose of 100 μg SC.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

4. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

1. Have been informed of other treatment options.

2. Age ≥ 18 years.

3. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
2	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016

Sponsors and Collaborators

• Ludwig Institute for Cancer Research
• Roswell Park Cancer Institute
• New York University Cancer Institute

Investigators

• Study Chair: Kunle Odunsi, MD, PhD, Roswell Park Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT00803569
• Other Study ID Numbers: LUD2007-005; CDR0000628730
• First Posted: Dec 5, 2008
• Last Update Posted: Feb 15, 2019
• Last Verified: Sep 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ludwig Institute for Cancer Research: recurrent ovarian epithelial cancer; stage II ovarian epithelial cancer; stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; fallopian tube cancer; peritoneal cavity cancer
• Additional relevant MeSH terms: Fallopian Tube Neoplasms; Sargramostim

Study Results

Participant Flow

Arm/Group Title	ALVAC(2)-NY-ESO-1(M)/TRICOM + GM-CSF
Arm/Group Description	Patients received subcutaneous (SC) injections with ALVAC(2)-NY-ESO-1(M)/TRICOM (0.5 mL) on Day 1 and the granulocyte macrophage-colony stimulating factor (GM-CSF) sargramostim (100 μg) on Days 1 through 4 in continuous 28-day cycles for up to 6 cycles.
Period Title: Overall Study
STARTED	13
COMPLETED	9
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	ALVAC(2)-NY-ESO-1(M)/TRICOM + GM-CSF
Arm/Group Description	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.
Overall Participants	13
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.5 (9.5)
Sex: Female, Male (Count of Participants)
Female	13 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	13 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	13 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	13 100%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.7 (5.2)

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Treatment-emergent Adverse Events
Description	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.
Time Frame	Continuously for up to 26 weeks

Outcome Measure Data

Analysis Population Description

Patients who received at least 1 dose of study drug.

Arm/Group Title	ALVAC(2)-NY-ESO-1(M)/TRICOM + GM-CSF
Arm/Group Description	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.
Measure Participants	13
Any TEAE	12 92.3%
Maximum Grade 1 TEAE	6 46.2%
Maximum Grade 2 TEAE	6 46.2%
Treatment-related TEAE	12 92.3%
SeriousTEAE	0 0%
Death	0 0%
TEAE Leading to Discontinuation	0 0%

2. Secondary Outcome

Title	Number of Patients With Best Overall Tumor Response
Description	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.
Time Frame	Baseline and Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

Patients with data available from at least 1 post-baseline response assessment. One patient discontinued the study prior to the Week 12 response assessment.

Arm/Group Title	ALVAC(2)-NY-ESO-1(M)/TRICOM + GM-CSF
Arm/Group Description	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.
Measure Participants	12
No evidence of disease	10 76.9%
Progressive disease	2 15.4%

3. Secondary Outcome

Title	Median Progression-free Survival (PFS)
Description	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.
Time Frame	Baseline and up to approximately 24 weeks

Outcome Measure Data

Analysis Population Description

Patients with data available from at least 1 post-baseline response assessment. One patient discontinued the study prior to the Week 12 response assessment.

Arm/Group Title	ALVAC(2)-NY-ESO-1(M)/TRICOM + GM-CSF
Arm/Group Description	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.
Measure Participants	12
Median (Full Range) [days]	167.5

4. Secondary Outcome

Title	Median Cancer Antigen 25 (CA-125) Values on Study
Description	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.
Time Frame	Baseline through Week 24

Outcome Measure Data

Analysis Population Description

Patients with data available from at least 1 post-baseline response assessment. One patient discontinued the study prior to the Week 12 response assessment.

Arm/Group Title	ALVAC(2)-NY-ESO-1(M)/TRICOM + GM-CSF
Arm/Group Description	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.
Measure Participants	12
Baseline	8.6
Week 8	9.7
Week 12	7.4
Week 16	9.4
Week 20	9.0
Week 24	8.0

5. Secondary Outcome

Title	Number of Patients With NY-ESO-1 and LAGE-1 Antigen Positivity
Description	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).
Time Frame	Baseline through Week 24

Outcome Measure Data

Analysis Population Description

Patients with data available from at least 1 post-baseline response assessment. One patient discontinued the study prior to the Week 12 response assessment.

Arm/Group Title	ALVAC(2)-NY-ESO-1(M)/TRICOM + GM-CSF
Arm/Group Description	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.
Measure Participants	12
NY-ESO-1: BL positive, Post-BL positive	2 15.4%
NY-ESO-1: BL negative, Post-BL positive	10 76.9%
LAGE-1: BL positive, Post-BL positive	1 7.7%
LAGE-1: BL negative, Post-BL positive	3 23.1%
LAGE-1: BL negative, Post-BL negative	2 15.4%
LAGE-1: Not evaluable	6 46.2%

Adverse Events

Time Frame	All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs). The AE reporting period for this study was up to 26 weeks.
Adverse Event Reporting Description	AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 3.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per patient at the maximum reported grade.
Arm/Group Title	ALVAC(2)-NY-ESO-1(M)/TRICOM + GM-CSF
Arm/Group Description	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.
All Cause Mortality
	ALVAC(2)-NY-ESO-1(M)/TRICOM + GM-CSF
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Serious Adverse Events
	ALVAC(2)-NY-ESO-1(M)/TRICOM + GM-CSF
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Other (Not Including Serious) Adverse Events
	ALVAC(2)-NY-ESO-1(M)/TRICOM + GM-CSF
	Affected / at Risk (%)	# Events
Total	12/13 (92.3%)
Cardiac disorders
Palpitations	1/13 (7.7%)
Gastrointestinal disorders
Abdominal pain	1/13 (7.7%)
Flatulence	1/13 (7.7%)
Nausea	1/13 (7.7%)
Oral pain	1/13 (7.7%)
General disorders
Injection site pain	8/13 (61.5%)
Injection site erythema	7/13 (53.8%)
Injection site reaction	6/13 (46.2%)
Fatigue	5/13 (38.5%)
Injection site induration	4/13 (30.8%)
Injection site pruritus	2/13 (15.4%)
Injection site rash	2/13 (15.4%)
Chills	1/13 (7.7%)
Hypothermia	1/13 (7.7%)
Influenza-like illness	1/13 (7.7%)
Injection site nodule	1/13 (7.7%)
Injection site swelling	1/13 (7.7%)
Oedema	1/13 (7.7%)
Oedema peripheral	1/13 (7.7%)
Infections and infestations
Vaginal infection	2/13 (15.4%)
Acute sinusitis	1/13 (7.7%)
Nasopharyngitis	1/13 (7.7%)
Rhinitis	1/13 (7.7%)
Injury, poisoning and procedural complications
Contusion	1/13 (7.7%)
Investigations
Skin test positive	1/13 (7.7%)
Metabolism and nutrition disorders
Anorexia	1/13 (7.7%)
Musculoskeletal and connective tissue disorders
Myalgia	4/13 (30.8%)
Back pain	2/13 (15.4%)
Arthralgia	1/13 (7.7%)
Nervous system disorders
Headache	5/13 (38.5%)
Dizziness	1/13 (7.7%)
Reproductive system and breast disorders
Vulvovaginal pruritus	1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	2/13 (15.4%)
Cough	1/13 (7.7%)
Nasal congestion	1/13 (7.7%)
Skin and subcutaneous tissue disorders
Pruritus	4/13 (30.8%)
Ecchymosis	1/13 (7.7%)
Erythema	1/13 (7.7%)
Rash	1/13 (7.7%)
Rash pruritic	1/13 (7.7%)
Vascular disorders
Flushing	1/13 (7.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.