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

Primary Purpose

Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma

Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Laboratory Biomarker Analysis
Recombinant NY-ESO-1 Protein
Sirolimus
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Fallopian Tube Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • 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 by immunohistochemistry (IHC) and/or real-time polymerase chain reaction (RTPCR)
  • No history of previous severe allergic reactions to vaccines or unknown allergens
  • Life expectancy > 6 months
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • 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
  • Platelets (PLT) >= 75,000/uL
  • Hemoglobin (Hgb) >= 8 g/dL
  • Total bilirubin =< 1.5 x upper limits of normal (ULN)
  • Serum glutamic-oxaloacetic transaminase(SGOT)/aspartate aminotransferase (AST) or serum glutamate pyruvate 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 indications of cardiac problems like congestive heart failure, myocardial infarction, and cardiomyopathy
  • Have been informed of other treatment options
  • Ability to swallow and retain oral medication
  • Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control) prior to study entry; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately
  • Participant 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
  • Patients may have received previous NY-ESO-1 vaccine therapy

Exclusion Criteria:

  • Metastatic disease to the central nervous system
  • 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 non-steroidal antiinflammatory drugs for >2 weeks,, and other platelet inhibitory agents, strong inhibitors/inducers of cytochrome P450-3A4 (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
  • Patients with a positive fecal occult blood test excluding hemorrhoids
  • Clinically significant heart disease (New York Heart Association [NYHA] class III or IV) within six months
  • 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 human immunodeficiency virus (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)

Sites / Locations

  • Roswell Park Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Cohort I (NY-ESO-1 protein with MIS416)

Cohort II (NY-ESO-1 protein with MIS416, sirolimus)

Arm Description

Patients receive NY-ESO-1 protein with MIS416 vaccine SC on days 1, 15, 29, 57, 85, and 113 in the absence of disease progression or toxicity.

Patients receive NY-ESO-1 protein with MIS416 vaccine as in Cohort I. Patients also receive sirolimus PO daily for 2 weeks followed by 2 weeks off starting on days 1, 29, 57, and 85.

Outcomes

Primary Outcome Measures

Incidence of adverse events defined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
The toxicity rate for each adverse event will be estimated using a two-sided, 95%, exact binomial confidence interval (Clopper-Pearson).

Secondary Outcome Measures

NY-ESO-1 specific CD4+ and CD8+ T-cells cellular immunity assessed in peripheral blood by enzyme-linked immunosorbent spot (ELISPOT) and intracellular cytokine staining (ICS)
Assessed iin peripheral blood by enzyme-linked immunosorbent spot (ELISPOT) and intracellular cytokine staining (ICS)
NY-ESO-1 specific humoral immunity
assessed in peripheral blood by ELISA
Time to disease progression as documented by Response Evaluation Criteria in Solid Tumors version 1.1

Full Information

First Posted
July 8, 2016
Last Updated
April 27, 2018
Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02833506
Brief Title
Sirolimus and Vaccine Therapy in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Official Title
A Phase I Clinical Trial of mTOR Inhibition With Sirolimus for Enhancing NY-ESO-1 Protein With MIS416 Vaccine Induced Anti-Tumor Immunity in Ovarian, Fallopian Tube and Primary Peritoneal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Withdrawn
Why Stopped
production of adjuvant to be used with vaccine was discontinued by sponsor
Study Start Date
December 8, 2017 (Actual)
Primary Completion Date
August 15, 2018 (Anticipated)
Study Completion Date
August 15, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase I clinical trial studies the side effects of sirolimus and NY-ESO-1 protein with MIS416 in treating patients stage II-IV ovarian, fallopian tube, or primary peritoneal cancer. Sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vaccine therapy, like Y-ESO-1 protein with MIS416, may strengthen the immune system to find and kill tumor cells. Biological therapies, such as sirolimus, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Giving sirolimus and vaccine therapy may work betting in treating patients with ovarian, fallopian tube or primary peritoneal cancer.
Detailed Description
PRIMARY OBJECTIVE: I. Determine the safety and feasibility of NY-ESO-1 protein with MIS416 in combination with mammalian target of rapamycin (mTOR) inhibitor sirolimus. SECONDARY OBJECTIVES: I. To determine the effectiveness of these combinatorial therapies 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; explore time to disease progression. OUTLINE: COHORT I (C1): Patients receive NY-ESO-1 protein with MIS416 vaccine subcutaneously (SC) on days 1, 15, 29, 57, 85, and 113 in the absence of disease progression or toxicity. COHORT II (C2): Patients receive NY-ESO-1 protein with MIS416 vaccine as in Cohort I. Patients also receive sirolimus orally (PO) daily for 2 weeks followed by 2 weeks off starting on days 1, 29, 57, and 85. After completion of study treatment, patients are followed up at 30 days and then at 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma, Stage IIA Fallopian Tube Cancer, Stage IIA Ovarian Cancer, Stage IIB Fallopian Tube Cancer, Stage IIB Ovarian Cancer, Stage IIC Fallopian Tube Cancer, Stage IIC Ovarian Cancer, Stage IIIA Fallopian Tube Cancer, Stage IIIA Ovarian Cancer, Stage IIIA Primary Peritoneal Cancer, Stage IIIB Fallopian Tube Cancer, Stage IIIB Ovarian Cancer, Stage IIIB Primary Peritoneal Cancer, Stage IIIC Fallopian Tube Cancer, Stage IIIC Ovarian Cancer, Stage IIIC Primary Peritoneal Cancer, Stage IV Fallopian Tube Cancer, Stage IV Ovarian Cancer, Stage IV Primary Peritoneal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort I (NY-ESO-1 protein with MIS416)
Arm Type
Active Comparator
Arm Description
Patients receive NY-ESO-1 protein with MIS416 vaccine SC on days 1, 15, 29, 57, 85, and 113 in the absence of disease progression or toxicity.
Arm Title
Cohort II (NY-ESO-1 protein with MIS416, sirolimus)
Arm Type
Experimental
Arm Description
Patients receive NY-ESO-1 protein with MIS416 vaccine as in Cohort I. Patients also receive sirolimus PO daily for 2 weeks followed by 2 weeks off starting on days 1, 29, 57, and 85.
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Biological
Intervention Name(s)
Recombinant NY-ESO-1 Protein
Intervention Description
Given recombinant NY-ESO-1 protein SC
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Other Intervention Name(s)
AY 22989, RAPA, Rapamune, RAPAMYCIN, SILA 9268A, WY-090217
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Incidence of adverse events defined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
Description
The toxicity rate for each adverse event will be estimated using a two-sided, 95%, exact binomial confidence interval (Clopper-Pearson).
Time Frame
Up to 30 days
Secondary Outcome Measure Information:
Title
NY-ESO-1 specific CD4+ and CD8+ T-cells cellular immunity assessed in peripheral blood by enzyme-linked immunosorbent spot (ELISPOT) and intracellular cytokine staining (ICS)
Description
Assessed iin peripheral blood by enzyme-linked immunosorbent spot (ELISPOT) and intracellular cytokine staining (ICS)
Time Frame
Up to 12 months
Title
NY-ESO-1 specific humoral immunity
Description
assessed in peripheral blood by ELISA
Time Frame
Up to 12 months
Title
Time to disease progression as documented by Response Evaluation Criteria in Solid Tumors version 1.1
Time Frame
Up to 12 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 by immunohistochemistry (IHC) and/or real-time polymerase chain reaction (RTPCR) No history of previous severe allergic reactions to vaccines or unknown allergens Life expectancy > 6 months Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 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 Platelets (PLT) >= 75,000/uL Hemoglobin (Hgb) >= 8 g/dL Total bilirubin =< 1.5 x upper limits of normal (ULN) Serum glutamic-oxaloacetic transaminase(SGOT)/aspartate aminotransferase (AST) or serum glutamate pyruvate 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 indications of cardiac problems like congestive heart failure, myocardial infarction, and cardiomyopathy Have been informed of other treatment options Ability to swallow and retain oral medication Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control) prior to study entry; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately Participant 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 Patients may have received previous NY-ESO-1 vaccine therapy Exclusion Criteria: Metastatic disease to the central nervous system 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 non-steroidal antiinflammatory drugs for >2 weeks,, and other platelet inhibitory agents, strong inhibitors/inducers of cytochrome P450-3A4 (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 Patients with a positive fecal occult blood test excluding hemorrhoids Clinically significant heart disease (New York Heart Association [NYHA] class III or IV) within six months 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 human immunodeficiency virus (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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kunle Odunsi
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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