Sirolimus and Vaccine Therapy in Treating Patients With Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer
A Phase I Clinical Trial of mTOR Inhibition With Sirolimus for Enhancing ALVAC(2)-NY-ESO-1(M)/TRICOM Vaccine Induced Anti-Tumor Immunity in Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
2 other identifiers
interventional
7
1 country
1
Brief Summary
This phase I trial studies the side effects and best dose and schedule of sirolimus when given together with vaccine therapy in treating patients with stage II-IV ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer. Sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Giving vaccine therapy together with sirolimus may be an effective treatment for ovarian, fallopian tube, or primary peritoneal cancer
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Aug 2012
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 30, 2011
CompletedFirst Posted
Study publicly available on registry
February 20, 2012
CompletedStudy Start
First participant enrolled
August 20, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 21, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
April 21, 2015
CompletedMarch 27, 2020
March 1, 2020
2.7 years
December 30, 2011
March 25, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Safety of ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine in combination with varying dose levels and schedules of sirolimus, assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4
The toxicity rate will be estimated using a one-sided, 95%, exact binomial confidence interval (Clopper-Pearson). The lower one sided limit will be used.
Up to 30 days after completion of study treatment
Secondary Outcomes (7)
Effectiveness of sirolimus on enhancing vaccine efficacy, assessed by NY-ESO-1 specific cellular and humoral immunity
Up to 1 year
Antibody titers
At baseline, days 29, 57, 85, 141, and at 6 weeks-post treatment
NY-ESO-1 specific CD8+ and CD4+ frequency and function
At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment
Frequency of memory T-cell populations
At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment
TCR avidity
At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment
- +2 more secondary outcomes
Study Arms (1)
Treatment (vaccine, sirolimus, GM-CSF)
EXPERIMENTALPatients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1 and GM-CSF SC on days 1-4. Patients also receive sirolimus PO QD on days 1-14 OR 15-28 OR 1-28. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive an additional course of ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine only followed by ALVAC(2)-NY-ESO-I (M)/TRICOM vaccine SC 8 weeks after completion of course 4.
Interventions
Given SC
Given PO
Given SC
Eligibility Criteria
You may qualify if:
- Eligible patients will be women with stages II-IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who have completed standard therapy for primary or recurrent disease (i.e., patients who would normally be observed); eligible patients may have asymptomatic residual measurable disease on physical examination and/or computed tomography (CT) scan, and/or may have an elevated cancer antigen 125 (CA-125); or may be in complete clinical remission after treatment for primary or recurrent disease; these patients would normally enter a period of observation after standard management
- Any human leukocyte antigen (HLA) type; (historic HLA typing is permitted)
- Tumor expression of NY-ESO-1 or cancer/testis antigen 2 (LAGE-1) by immunohistochemistry (IHC) and/or real-time polymerase chain reaction (RT-PCR)
- No allergy to eggs
- Life expectancy \> 6 months
- Hematology and biochemistry laboratory results within the limits normally expected for the patient population, without evidence of major organ failure
- Absolute neutrophil count (ANC) \>= 1,000/uL
- Platelet \>= 75,000/uL
- Hemoglobin (Hgb) \>= 8 g/dL
- Total bilirubin =\< 1.5 x upper limit of normal (ULN)
- Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) =\< 3 x ULN
- Serum creatinine =\< 2 x ULN
- Prothrombin time (PT)/international normalized ratio (INR) =\< 1.5
- Electrocardiogram, showing no evidence of congestive heart failure, myocardial infarction, and cardiomyopathy
- Have been informed of other treatment options
- +5 more criteria
You may not qualify if:
- Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available
- Other serious illnesses (e.g. serious infections requiring antibiotics, bleeding disorders)
- History of severe autoimmune disorders requiring use of steroids or other immunosuppressives
- Concomitant systemic treatment with corticosteroids, anti-histamine or nonsteroidal anti-inflammatory drugs and other platelet inhibitory agents, strong inhibitors/inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450-3A4)
- Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing of study drug (6 weeks for nitrosoureas); concomitant hormonal therapies for breast cancers are allowed
- Known allergy or history of life threatening reaction to GM-CSF
- Clinically significant heart disease (N-YHA Class III or IV)
- Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing of study drug
- Known hepatitis B, hepatitis C, or HIV
- Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study
- Lack of availability of a patient for immunological and clinical follow-up assessment
- Known pulmonary hypertension
- Known hypersensitivity to sirolimus
- Evidence of current drug or alcohol abuse or psychiatric impairment, which in the investigator's opinion will prevent completion of the protocol therapy or follow-up
- Pregnant or nursing female patients
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Roswell Park Cancer Institutelead
- National Cancer Institute (NCI)collaborator
- Sanofi Pasteur, a Sanofi Companycollaborator
Study Sites (1)
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Related Publications (5)
Odunsi K, Matsuzaki J, James SR, Mhawech-Fauceglia P, Tsuji T, Miller A, Zhang W, Akers SN, Griffiths EA, Miliotto A, Beck A, Batt CA, Ritter G, Lele S, Gnjatic S, Karpf AR. Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer. Cancer Immunol Res. 2014 Jan;2(1):37-49. doi: 10.1158/2326-6066.CIR-13-0126.
PMID: 24535937BACKGROUNDLiao J, Qian F, Tchabo N, Mhawech-Fauceglia P, Beck A, Qian Z, Wang X, Huss WJ, Lele SB, Morrison CD, Odunsi K. Ovarian cancer spheroid cells with stem cell-like properties contribute to tumor generation, metastasis and chemotherapy resistance through hypoxia-resistant metabolism. PLoS One. 2014 Jan 7;9(1):e84941. doi: 10.1371/journal.pone.0084941. eCollection 2014.
PMID: 24409314BACKGROUNDGodoy HE, Khan AN, Vethanayagam RR, Grimm MJ, Singel KL, Kolomeyevskaya N, Sexton KJ, Parameswaran A, Abrams SI, Odunsi K, Segal BH. Myeloid-derived suppressor cells modulate immune responses independently of NADPH oxidase in the ovarian tumor microenvironment in mice. PLoS One. 2013 Jul 26;8(7):e69631. doi: 10.1371/journal.pone.0069631. Print 2013.
PMID: 23922763BACKGROUNDMatsuzaki J, Tsuji T, Luescher I, Old LJ, Shrikant P, Gnjatic S, Odunsi K. Nonclassical antigen-processing pathways are required for MHC class II-restricted direct tumor recognition by NY-ESO-1-specific CD4(+) T cells. Cancer Immunol Res. 2014 Apr;2(4):341-50. doi: 10.1158/2326-6066.CIR-13-0138. Epub 2013 Dec 17.
PMID: 24764581BACKGROUNDWithers 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.
PMID: 40132910DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Kunle Odunsi
Roswell Park Cancer Institute
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 30, 2011
First Posted
February 20, 2012
Study Start
August 20, 2012
Primary Completion
April 21, 2015
Study Completion
April 21, 2015
Last Updated
March 27, 2020
Record last verified: 2020-03