Brief Title
Vaccine Therapy and IDO1 Inhibitor INCB024360 in Treating Patients With Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Are in Remission
Official Title
A Phase I/IIb Study of Recombinant ALVAC(2)-NY-ESO-1 (M)/TRICOM in Combination With INCB024360 for Patients in Remission With Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma Whose Tumors Express NY-ESO-1 or LAGE-1 Antigen
Brief Summary
This partially randomized phase I/IIb trial studies the side effects vaccine therapy and
indoleamine 2,3-dioxygenase (IDO1) inhibitor 4-amino-1,2,5-oxadizaole-3-carboximidamide
(INCB024360) and to see how well they work in treating patients with epithelial ovarian,
fallopian tube, or primary peritoneal cancer who are in remission. Vaccines made from
gene-modified virus may help the body build an effective immune response to kill tumor cells.
IDO1 inhibitor INCB024360 may stop the growth of tumor cells by blocking some of the enzymes
needed for cell growth. Giving vaccine therapy with IDO1 inhibitor INCB024360 may be an
effective treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the safety of fixed doses of the modified canarypox vector
(ALVAC[2])-cancer/testis antigen 1B (NY-ESO-1) (M)/triad of costimulatory molecules (TRICOM)
vaccine in combination with INCB024360 (IDO1 inhibitor INCB024360). (Phase I) II. To evaluate
toxicity as defined by National Cancer Institute (NCI) Common Terminology Criteria for
Adverse Events (CTCAE) version 4.0. (Phase I) III. To determine the progression free survival
(PFS) using standard imaging response (Response Evaluation Criteria in Solid Tumors [RECIST]
1.1) criteria. (Phase IIb)
SECONDARY OBJECTIVES:
I. To determine the effectiveness of INCB024360 on enhancing vaccine efficacy by assessing
NY-ESO-1 specific cellular and humoral immunity in peripheral blood NY-ESO-1 specific CD8+
and CD4+ T cells.
II. To determine the effectiveness of INCB024360 on enhancing vaccine efficacy by assessing
NY-ESO-1 specific cellular and humoral immunity in peripheral blood NY-ESO-1 specific
antibodies.
III. To determine the effectiveness of INCB024360 on enhancing vaccine efficacy by assessing
NY-ESO-1 specific cellular and humoral immunity in peripheral blood frequency of
CD4+CD25+FOXP3+ regulatory T cells.
IV. To determine the effectiveness of INCB024360 on enhancing vaccine efficacy by assessing
NY-ESO-1 specific cellular and humoral immunity in pharmacokinetics (PK) of IDO in relation
to T cell frequency and function in correlation with PFS.
OUTLINE: This is a Phase I study followed by a randomized Phase IIb study.
PHASE I: Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine subcutaneously (SC) on day 1
and IDO1 inhibitor INCB024360 orally (PO) twice daily (BID) on days 1-28. Treatment repeats
every 28 days for up to 6 courses in the absence of disease progression or unacceptable
toxicity.
PHASE IIb: Patients are randomized to 1 of 4 arms.
ARM A: Patients receive no treatment.
ARM B: Patients receive IDO1 inhibitor INCB024360 PO BID on days 1-28.
ARM C: Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1 and IDO1 inhibitor
INCB024360 PO BID on days 1-28.
ARM D: Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1.
In all arms, treatment repeats every 28 days in the absence of disease progression or
unacceptable toxicity.
After completion of study treatment, patients are followed up at 6 weeks; at 3, 6, and 12
months; and then annually for up to 15 years.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Maximum tolerated dose of IDO1 inhibitor INCB024360, determined by incidence of dose limiting toxicities graded according to the NCI CTCAE version 4.0 (Phase I)
Secondary Outcome
Immunological response
Condition
Recurrent Fallopian Tube Cancer
Intervention
ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine
Study Arms / Comparison Groups
Arm A (no treatment)
Description: Patients receive no treatment.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
0
Start Date
December 2013
Primary Completion Date
September 2017
Eligibility Criteria
Inclusion Criteria:
- Women with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and no
evidence of disease or no measurable disease after 1st or 2nd line therapy; 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 reverse transcription-polymerase chain reaction
(RTPCR)
- 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 count (PLT) >= 75,000/uL
- Hemoglobin (Hgb) >= 8g/dL
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Serum aspartate aminotransferase (serum glutamic oxalacetic transaminase
[SGOT]/aspartate aminotransferase [AST]) or serum alanine aminotransferase (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
- 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
- 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; patients who received
maintenance paclitaxel or bevacizumab are eligible for enrollment provided they have
discontinued therapy (at least 4 weeks for prior taxane) prior to randomization and
recovered from toxicities to less than grade 2
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 non-steroidal
anti-inflammatory drugs, and other platelet inhibitory agents
- 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
- Clinically significant heart disease (New York Heart Association [NYHA] class III or
class IV) within 6 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
- 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 judgement, increase the patient's
risk by participating in this study)
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Kunle Odunsi, ,
Administrative Informations
NCT ID
NCT01982487
Organization ID
I 243013
Secondary IDs
NCI-2013-02080
Responsible Party
Sponsor
Study Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Kunle Odunsi, Principal Investigator, Roswell Park Cancer Institute
Verification Date
December 2013