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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


Phase 1
18 Years
N/A
Open (Enrolling)
Female
Recurrent Fallopian Tube Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer, Stage IIA Fallopian Tube Cancer, Stage IIA Ovarian Epithelial Cancer, Stage IIA Primary Peritoneal Cavity Cancer, Stage IIB Fallopian Tube Cancer, Stage IIB Ovarian Epithelial Cancer, Stage IIB Primary Peritoneal Cavity Cancer, Stage IIC Fallopian Tube Cancer, Stage IIC Ovarian Epithelial Cancer, Stage IIC Primary Peritoneal Cavity Cancer, Stage IIIA Fallopian Tube Cancer, Stage IIIA Ovarian Epithelial Cancer, Stage IIIA Primary Peritoneal Cavity Cancer, Stage IIIB Fallopian Tube Cancer, Stage IIIB Ovarian Epithelial Cancer, Stage IIIB Primary Peritoneal Cavity Cancer, Stage IIIC Fallopian Tube Cancer, Stage IIIC Ovarian Epithelial Cancer, Stage IIIC Primary Peritoneal Cavity Cancer, Stage IV Fallopian Tube Cancer, Stage IV Ovarian Epithelial Cancer, Stage IV Primary Peritoneal Cavity Cancer

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Trial Information

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


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.


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)

- 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

- No immunodeficiency; i.e., subjects must be human immunodeficiency virus (HIV)
negative based on baseline testing

- Have been informed of other treatment options

- No acute or chronic hepatitis (hepatitis B surface antigen [HbsAg]) positive or
hepatitis C virus (anti-HCV) positive patients based on baseline testing

- Patient or legal representative must understand the investigational nature of this
study and sign an Independent Ethics Committee/Institutional Review Board approved
written informed consent form prior to receiving any study related procedure

- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 2

- Demonstrate the ability to swallow and retain oral medication

- Patients of child-bearing potential must agree to use acceptable contraceptive
methods (e.g., double barrier) during treatment

- Patients may have received previous NY-ESO-1 vaccine therapy

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

- Concomitant systemic treatment with corticosteroids, anti-histamine or nonsteroidal
anti-inflammatory drugs, aspirin > 325 mg, 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

- 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

- Unwilling or unable to follow protocol requirements

- Any condition which in the investigator's opinion deems the patient an unsuitable
candidate to receive study drug; (i.e., any significant medical illness or abnormal
laboratory finding that would, in the investigator's judgment, increase the subject's
risk by participating in this study)

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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.

Outcome Time Frame:

Up to 30 days after completion of study treatment

Safety Issue:

Yes

Principal Investigator

Kunle Odunsi

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

I 199911

NCT ID:

NCT01536054

Start Date:

August 2012

Completion Date:

Related Keywords:

  • Recurrent Fallopian Tube Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Primary Peritoneal Cavity Cancer
  • Stage IIA Fallopian Tube Cancer
  • Stage IIA Ovarian Epithelial Cancer
  • Stage IIA Primary Peritoneal Cavity Cancer
  • Stage IIB Fallopian Tube Cancer
  • Stage IIB Ovarian Epithelial Cancer
  • Stage IIB Primary Peritoneal Cavity Cancer
  • Stage IIC Fallopian Tube Cancer
  • Stage IIC Ovarian Epithelial Cancer
  • Stage IIC Primary Peritoneal Cavity Cancer
  • Stage IIIA Fallopian Tube Cancer
  • Stage IIIA Ovarian Epithelial Cancer
  • Stage IIIA Primary Peritoneal Cavity Cancer
  • Stage IIIB Fallopian Tube Cancer
  • Stage IIIB Ovarian Epithelial Cancer
  • Stage IIIB Primary Peritoneal Cavity Cancer
  • Stage IIIC Fallopian Tube Cancer
  • Stage IIIC Ovarian Epithelial Cancer
  • Stage IIIC Primary Peritoneal Cavity Cancer
  • Stage IV Fallopian Tube Cancer
  • Stage IV Ovarian Epithelial Cancer
  • Stage IV Primary Peritoneal Cavity Cancer
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263