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
Overview
- Phase
- Phase 1
- Intervention
- ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine
- Conditions
- Recurrent Fallopian Tube Cancer
- Sponsor
- Roswell Park Cancer Institute
- Enrollment
- 7
- Locations
- 1
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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
Detailed Description
PRIMARY OBJECTIVES: I. Determine the safety of ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine with sirolimus at varying dose and schedule. SECONDARY OBJECTIVES: I. To determine the effectiveness of sirolimus on enhancing vaccine efficacy by assessing NY-ESO-1 specific cellular and humoral immunity: peripheral blood NY-ESO-1 specific cluster of differentiation (CD)8+ and CD4+ T-cells; peripheral blood NY-ESO-1 specific antibodies; peripheral blood frequency of CD4+CD25+forkhead box P3 (FOXP3)+ regulatory T-cells. II. Explore time to disease progression. OUTLINE: This is a dose-escalation study of sirolimus. Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine subcutaneously (SC) on day 1 and sargramostim (GM-CSF) SC on days 1-4. Patients also receive sirolimus orally (PO) once daily (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. After completion of study treatment, patients are followed up at 30 days, and 6 and 12 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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)
Exclusion Criteria
- •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
Arms & Interventions
Treatment (vaccine, sirolimus, GM-CSF)
Patients 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.
Intervention: ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine
Treatment (vaccine, sirolimus, GM-CSF)
Patients 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.
Intervention: sirolimus
Treatment (vaccine, sirolimus, GM-CSF)
Patients 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.
Intervention: laboratory biomarker analysis
Treatment (vaccine, sirolimus, GM-CSF)
Patients 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.
Intervention: sargramostim
Outcomes
Primary Outcomes
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
Time Frame: Up to 30 days after completion of study treatment
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.
Secondary Outcomes
- 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)
- Secondary recall response(Up to 1 year)
- Time to disease progression(Up to 1 year)
- Effectiveness of sirolimus on enhancing vaccine efficacy, assessed by NY-ESO-1 specific cellular and humoral immunity(Up to 1 year)