Trial record 1 of 1 for:    NCT01536054
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Sirolimus and Vaccine Therapy in Treating Patients With Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Roswell Park Cancer Institute
Sponsor:
Collaborators:
Sanofi Pasteur, a Sanofi Company
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01536054
First received: December 30, 2011
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
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
Biological: ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine
Drug: sirolimus
Other: laboratory biomarker analysis
Biological: sargramostim
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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 Outcome Measures:
  • Effectiveness of sirolimus on enhancing vaccine efficacy, assessed by NY-ESO-1 specific cellular and humoral immunity [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    The following parameters will be determined: (I) generation of memory T-cells with (2) high avidity that are also (3) resistant to regulatory T cells (Tregs): (4) secondary recall responses. Analyzed via an analysis-of-covariance (ANCOVA) model with post-treatment levels modeled as a function pretreatment levels and main effects corresponding to the 3 x 3 design. The biological signal across all cohorts will be tested on whether or not the slope parameter is 0 or not.

  • Antibody titers [ Time Frame: At baseline, days 29, 57, 85, 141, and at 6 weeks-post treatment ] [ Designated as safety issue: No ]
    Will be analyzed via an ANCOVA model with post-treatment levels modeled as a function pretreatment levels and main effects corresponding to the 3 x 3 design.

  • NY-ESO-1 specific CD8+ and CD4+ frequency and function [ Time Frame: At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment ] [ Designated as safety issue: No ]
    The analysis of continuous immunological response endpoints will be analyzed via an ANCOVA model with post-treatment levels modeled as a function pretreatment levels and main effects corresponding to the 3 x 3 design.

  • Frequency of memory T-cell populations [ Time Frame: At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment ] [ Designated as safety issue: No ]
    The analysis of continuous immunological response endpoints will be analyzed via an ANCOVA model with post-treatment levels modeled as a function pretreatment levels and main effects corresponding to the 3 x 3 design.

  • TCR avidity [ Time Frame: At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment ] [ Designated as safety issue: No ]
    The analysis of continuous immunological response endpoints will be analyzed via an ANCOVA model with post-treatment levels modeled as a function pretreatment levels and main effects corresponding to the 3 x 3 design.

  • Secondary recall response [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    The analysis of continuous immunological response endpoints will be analyzed via an ANCOVA model with post-treatment levels modeled as a function pretreatment levels and main effects corresponding to the 3 x 3 design.

  • Time to disease progression [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: August 2012
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine
Given SC
Other Name: vCP2292
Drug: sirolimus
Given PO
Other Names:
  • AY 22989
  • Rapamune
  • rapamycin
  • SLM
Other: laboratory biomarker analysis
Correlative studies
Biological: sargramostim
Given SC
Other Names:
  • GM-CSF
  • Leukine
  • Prokine

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)
  • 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
  • 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 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
  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01536054

Locations
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Roswell Park    877-275-7724    ASKRPCI@roswellpark.org   
Principal Investigator: Kunle Odunsi         
Sponsors and Collaborators
Roswell Park Cancer Institute
Sanofi Pasteur, a Sanofi Company
Investigators
Principal Investigator: Kunle Odunsi Roswell Park Cancer Institute
  More Information

Publications:
Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT01536054     History of Changes
Other Study ID Numbers: I 199911, NCI-2011-02964
Study First Received: December 30, 2011
Last Updated: June 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Abdominal Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Ovarian Diseases
Endocrine System Diseases
Gonadal Disorders
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents

ClinicalTrials.gov processed this record on September 16, 2014