CYT107 After Vaccine Treatment (Provenge®) in Patients With Metastatic Castration-Resistant Prostate Cancer

Stage IV Prostate Cancer Clinical Trial

Official title:

Phase 2 Study of Recombinant Glycosylated Human Interleukin-7 (CYT107) After Completion of Standard Therapy With Sipuleucel-T (Provenge®) in Pts w/ Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer(mCRPC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01881867
• Other study ID #: CITN12-03
• Secondary ID: NCI-2013-00998CI
• Status: Completed
• Phase: Phase 2
• Start date: September 10, 2013
• Est. completion date: January 2, 2018

Study information

• Verified date: June 2019
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial studies how well glycosylated recombinant human interleukin-7 (CYT107) after vaccine therapy works in treating patients with castration-resistant prostate cancer that has spread to other areas of the body or has not responded to at least one type of treatment. Biological therapies, such as glycosylated recombinant human interleukin-7, may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines made from white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells. It is not yet known whether glycosylated recombinant human interleukin-7 works better with or without vaccine therapy in treating prostate cancer.

Description:

PRIMARY OBJECTIVES:

I. To determine whether CYT107 administration increases the vaccine-induced antigen-specific T-cell immune response to the sipuleucel-T fusion protein vaccine construct prostatic acid phosphatase granulocyte-macrophage colony-stimulating factor (PAP-GM-CSF) (PA2024).

SECONDARY OBJECTIVES:

I. To determine whether CYT107 administration increases the vaccine-induced antigen-specific T-cell immune response to PAP.

II. To assess the character of the T-cell immune response to PAP and PA2024. III. To determine whether CYT107 administration increases the vaccine-induced antigen-specific antibody immune responses to PAP and PA2024.

IV. To quantify the effects of CYT107 on T-cell repertoire diversity. V. To assess the effects of CYT107 on the immune competence of patients with advanced prostate cancer.

VI. To assess the clinical efficacy and tolerability of sipuleucel-T plus CYT107 compared with sipuleucel-T alone.

OUTLINE: Patients are randomized to 1 of 2 cohorts.

COHORT I: Patients receive no treatment (observation) after completion of standard sipuleucel-T therapy.

COHORT II: Patients receive glycosylated recombinant human interleukin-7 subcutaneously (SC) every week for 4 weeks (on days 0, 7, 14, and 21) beginning 3-7 days after completion of standard sipuleucel-T therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 53 weeks. Patients are followed by phone, once a year, after completion of Week 53 for overall survival.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: January 2, 2018
• Est. primary completion date: May 15, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)

• Patients must have successfully completed therapy with sipuleucel-T within 3-7 days of planned CYT107 study drug treatment

• Assessable disease with a positive bone scan and/or measurable disease on computed tomography (CT) scan and/or magnetic resonance imaging (MRI) of the abdomen and pelvis

• Prior orchiectomy or must be on ongoing luteinizing hormone-releasing hormone (LHRH) agonist or antagonist (e.g., degarelix) therapy

• No ongoing anti-androgen therapy; patients must be off anti-androgen therapy for at least 30 days

• Patients receiving any other hormonal therapy, including any dose of megestrol acetate (Megace), Proscar (finasteride), any herbal product known to decrease prostate specific antigen (PSA) levels (e.g. saw palmetto, PC-SPES), or any systemic corticosteroid, must discontinue the agent for at least 30 days prior to study treatment

• Absolute neutrophil count (ANC) >= 1500/uL

• Bilirubin < 1.5 x upper limit of normal (ULN)

• Hemoglobin >= 10 g/dL

• Platelets >= 100,000/mcL

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

• Creatinine clearance >= 60 mL/min by the Cockcroft-Gault equation

• Testosterone =< 50 ng/dL (documented at any time while on LHRH agonist or antagonists or s/p orchiectomy)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 or a Karnofsky performance status of >= 80%

• Life expectancy of at least 6 months

• Prior local radiation therapy must be completed at least 30 days prior to enrollment and the patient must have recovered from all toxicity

• Prior "systemic" radiopharmaceuticals (strontium, samarium, radium 223 dichloride) must be completed >= 8 weeks prior to enrollment

• Patients must agree to use 2 methods of adequate contraception for the duration of study participation, and for four months after discontinuing therapy

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior chemotherapy for castration resistant prostate cancer; neoadjuvant chemotherapy and chemotherapy given for hormone sensitive prostate cancer are allowed

• Prior investigational immunotherapy

• Prostate cancer pain requiring regularly scheduled narcotics

• Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression

• Current treatment with systemic steroid therapy (inhaled/topical steroids are acceptable); systemic corticosteroids must be discontinued for at least 30 days prior to first CYT107 injection

• Known central nervous system metastases

• Documented cirrhosis or documented acute hepatitis; Note: a positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface antibody [HBsAb] positive and hepatitis B core antibody [HBcAb] negative), or a fully resolved acute hepatitis B virus (HBV) infection is not an exclusion criterion

• History of severe asthma, as defined by prior or current use of systemic corticosteroids for disease control, with the exception of physiological replacement doses of cortisone acetate or equivalent, as defined by a dose of 10 mg or less

• Medical or psychiatric illness that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves

• Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months)

• Concurrent or prior malignancy except for the following:

• Adequately treated basal or squamous cell skin cancer

• Adequately treated stage I or II cancer from which the patient is currently in complete remission

• Any other cancer from which the patient has been disease-free for 5 years

• Known human immunodeficiency virus (HIV) or other history of immunodeficiency disorder; HIV-positive patients on combination antiretroviral therapy are ineligible

• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or medical (e.g. infectious) illness

• Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of CYT107 hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CYT107

• Patients who have received prior immunosuppressive therapy within 30 days prior to enrollment

• Active (as defined by requiring immunosuppressive therapy) or history of clinically significant autoimmune disease (as defined by previously requiring immunosuppressive therapy)

• Patients who have received hepatotoxic drugs less than 7 days prior to enrollment

• Patients who have received prior biologic agents less than 30 days prior to enrollment

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Patients who have a history of any hematopoietic malignancy

• History of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD), (forced expiratory volume [FEV] > 60% of predicted for height and age required in patients with prolonged smoking history or symptoms of respiratory dysfunction)

Related Conditions & MeSH terms

• Carcinoma
• Castration Levels of Testosterone
• Castration-Resistant Prostate Carcinoma
• Metastatic Prostate Carcinoma
• Prostatic Neoplasms
• Stage IV Prostate Cancer

Intervention

Biological:
• Glycosylated Recombinant Human Interleukin-7
Given SC

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	Cancer Immunotherapy Trials Network, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantification of T-cell Responses to Prostatic Acid Phosphatase Granulocyte-macrophage Colony-stimulating Factor (PAP-GM-CSF), Assessed by Quantification of Interferon Gamma Levels Measured Using Enzyme-linked Immunospot (ELISPOT)	The Mann-Whitney-Wilcoxon (MWW) test will be used as part of the statistical analysis to determine quantification of T-cell responses to prostatic acid phosphatase granulocyte-macrophage colony-stimulating factor (PAP-GM-CSF), as assessed by quantification of interferon gamma levels measured using enzyme-linked immunospot (ELISPOT). The power is roughly equivalent to that based on the t-test.	Day 70 (week 11)
Secondary	Change in Bystander Antigen Specific Immune Responses, Measured by Interferon Gamma Production in Response to Various Antigens as Quantified by Enzyme-linked Immunospot (ELISPOT)	Bystander antigen specific immune responses will be assessed to other ongoing and nascent antitumor responses (e.g., preferentially expressed antigen in melanoma, cancer/testis antigen 1B and/or tumor protein p53), additional tumor antigens specific to prostate cancer (e.g., prostate specific antigen [PSA] and/or prostate-specific membrane antigen), and memory viral responses (influenza A and cytomegalovirus, Epstein-Barr virus and influenza virus-derived peptides) using the interferon gamma ELISPOT assay.	Baseline to up to week 53
Secondary	Change in Circulating Tumor Cells	Enumerated by the approved Veridex assay.	Baseline to up to week 53
Secondary	Change in Number of Peripheral Blood Mononuclear Cell (PBMC) Subsets and T Lymphocyte Subsets	The absolute fold change from baseline of CD3+ cells	Week 11
Secondary	Change in Prostate Specific Antigen (PSA) Kinetics.	The change in prostate specific antigen (PSA) kinetics will be evaluated according to the recommendations from PSA Working Group (PSAWG). Analysis of PSA doubling time	Baseline to up to week 53
Secondary	Change in Vaccine-induced Antigen-specific Antibody Immune Response to Prostatic Acid Phosphatase (PAP)	Will be measured by change in immunoglobulin G (IgG) and immunoglobulin M (IgM) levels quantified by standard enzyme-linked immunosorbent assay (ELISA). Fold change from baseline in week 6 titer	Baseline to up to week 6
Secondary	Overall Survival	Number of participants that have survived	Up to 5 years