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Recurrent Fallopian Tube CancerPhase 1NCT01536054

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

A Phase 1 study testing ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine, sirolimus and laboratory biomarker analysis in people with Recurrent Fallopian Tube Cancer and Recurrent Ovarian Epithelial Cancer, run by Roswell Park Cancer Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine, sirolimus and laboratory biomarker analysis
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteUnited States
Study dates
20 Aug 2012to 21 Apr 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

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

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the safety of ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine with sirolimus at varying dose and schedule.

SECONDARY OBJECTIVES:

  1. 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.

Being tested
ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine, sirolimus, laboratory biomarker analysis, sargramostim
Medical subject headings
Fallopian Tube Neoplasms, Carcinoma, Ovarian Epithelial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccineBiological

    Also called vCP2292

    Given SC

  • sirolimusDrug

    Also called AY 22989, Rapamune, rapamycin, SLM

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

  • sargramostimBiological

    Also called GM-CSF, Leukine, Prokine

    Given SC

Study groups in NCT01536054
Study groupRoleWhat they receive
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.
Receives: Biological: ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine; Drug: sirolimus; Other: laboratory biomarker analysis; Biological: sargramostim

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 30 days after completion of study treatment

Secondary outcomes (7)

  1. Effectiveness of sirolimus on enhancing vaccine efficacy, assessed by NY-ESO-1 specific cellular and humoral immunity

    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.

    Measured: Up to 1 year

  2. Antibody titers

    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.

    Measured: At baseline, days 29, 57, 85, 141, and at 6 weeks-post treatment

  3. NY-ESO-1 specific CD8+ and CD4+ frequency and function

    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.

    Measured: At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment

  4. Frequency of memory T-cell populations

    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.

    Measured: At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment

  5. TCR avidity

    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.

    Measured: At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment

  6. Secondary recall response

    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.

    Measured: Up to 1 year

  7. Time to disease progression

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Feb 2012 (estimated)
  2. Study start20 Aug 2012
  3. Primary completion21 Apr 2015
  4. Study completion21 Apr 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01536054
Sponsor's protocol ID
I 199911
Other IDs
NCI-2011-02964
Status last verified
Mar 2020
First submitted
30 Dec 2011
Last updated
27 Mar 2020
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 24535937

  • Liao 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.

    PubMed 24409314

  • Godoy 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.

    PubMed 23922763

  • Matsuzaki 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.

    PubMed 24764581

  • Withers 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.

    PubMed 40132910

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine, sirolimus and laboratory biomarker analysis in people with Recurrent Fallopian Tube Cancer and Recurrent Ovarian Epithelial Cancer, run by Roswell Park Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary 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 (time frame: Up to 30 days after completion of study treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01536054, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2020.

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