Sirolimus and Vaccine Therapy in Treating Patients With Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer

March 25, 2020 updated by: Roswell Park Cancer Institute

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Other: laboratory biomarker analysis
Correlative studies
Drug: sirolimus
Given PO
Other Names:
  • Rapamune
  • AY 22989
  • rapamycin
  • SLM
Biological: sargramostim
Given SC
Other Names:
  • Leukine
  • Prokine
  • GM-CSF
Biological: ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine
Given SC
Other Names:
  • vCP2292

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 30 days after completion of study treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effectiveness of sirolimus on enhancing vaccine efficacy, assessed by NY-ESO-1 specific cellular and humoral immunity
Time Frame: Up to 1 year
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.
Up to 1 year
Antibody titers
Time Frame: At baseline, days 29, 57, 85, 141, and at 6 weeks-post treatment
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.
At baseline, days 29, 57, 85, 141, and at 6 weeks-post treatment
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
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.
At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment
Frequency of memory T-cell populations
Time Frame: At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment
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.
At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment
TCR avidity
Time Frame: At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment
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.
At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment
Secondary recall response
Time Frame: Up to 1 year
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.
Up to 1 year
Time to disease progression
Time Frame: Up to 1 year
Up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Roswell Park Cancer Institute

Collaborators

National Cancer Institute (NCI)
Sanofi Pasteur, a Sanofi Company

Investigators

  • Principal Investigator: Kunle Odunsi, Roswell Park Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 20, 2012

Primary Completion (Actual)

April 21, 2015

Study Completion (Actual)

April 21, 2015

Study Registration Dates

First Submitted

December 30, 2011

First Submitted That Met QC Criteria

February 15, 2012

First Posted (Estimate)

February 20, 2012

Study Record Updates

Last Update Posted (Actual)

March 27, 2020

Last Update Submitted That Met QC Criteria

March 25, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • I 199911
  • NCI-2011-02964 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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