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Safety and Tolerability Study of FolateImmune in Combination With Cytokines in Patients With Refractory or Metastatic Cancer

Primary Purpose

Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
EC90 (KLH-FITC)
GPI-0100
EC17 (Folate-FITC)
Interleukin-2
Interferon-alpha
Sponsored by
Endocyte
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer focused on measuring Cancer, Vaccine, Phase I, FolateImmune, Recurrent, Refractory, Experimental

Eligibility Criteria

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

Inclusion Criteria: Have a histologically confirmed diagnosis of metastatic or refractory cancer for which there are no effective standard therapeutic options available, (Note: for patients accrued at Southern Illinois University, a diagnosis of renal (i.e., kidney) carcinoma is required.) Have signed an Institutional Review Board (IRB) approved informed consent form (ICF) prior to performing any study evaluation/procedures Be > or = 18 years of age and women must either be 1) not of childbearing potential or 2) have a negative serum pregnancy test within 7 days prior to commencing treatment. Patients are considered not of childbearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or they are postmenopausal (12 consecutive months of amenorrhea [lack of menstruation]) (If applicable) Have completed prior cytotoxic chemotherapy, radiotherapy or immunotherapy or experimental therapy > or = 30 days prior to the study enrollment, and recovered form associated toxicities Have an Eastern Cooperative Oncology Group (ECOG) score of < or = 2, and an anticipated life expectancy of at least 6 months Have adequate hematologic function, as defined by an absolute or calculated neutrophil count > or = 1500/microL, platelet count > or = 100000/microL, lymphocyte count > or = 500/microL, and hemoglobin level > or = 10 g/dL. Patients may not receive prophylactic transfusion in order to qualify for trial eligibility Have adequate renal function, as defined by a documented serum creatinine of < or = 2.0mg/dL. Greater than "1+" proteinuria will require microscope evaluation and the results discussed with the medical monitor prior to patient enrollment; or if serum creatine is >2.0, patient must have an actual or calculated 24-hour creatinine clearance of >60mL/min and no obvious evidence of concurrent medullary cystic disease or obstructive uropathy Have adequate hepatic function, as defined by a total bilirubin level < or = 1.5 x upper limit of normal (ULN) and alkaline phosphatase, aspartate transaminase (AST), and alanine transaminase (ALT) levels < or = 2.5 x ULN. If alkaline phosphatase is outside of these parameters and is due to bone metastases (as verified by the assessment of isoenzymes), then the patient is eligible. Exclusion Criteria: Have previously participated in a FolateImmune trial Have a history of severe hypersensitivity (grade 3 - 4 allergic reaction) to fluorescein or any drug, radiologic contrast agent, insect bite, food, cytokines, or any other agent; or have received fluorescein within 30 days of the study. Have medical conditions that preclude the use of IL-2 or IFN-alpha. These conditions include but are not limited to, diabetes mellitus with a history of progression to diabetic ketoacidosis, history of severe coagulation disorder, psoriasis, sarcoidosis, retinal hemorrhage, symptomatic pulmonary disease, heart failure (> or = New York Heart Association NYHA class II), or transplant requiring immunosuppressive therapy Be pregnant or breast-feeding Be currently receiving an experimental drug, or used an experimental device within 30 days of study entry Be currently undergoing chemotherapy, anticancer hormonal therapy, and/or therapy with immunosuppressant agents Have any concomitant malignancy with the exception of basal cell or squamous cell carcinoma of skin Have radiographically documented evidence of current brain metastases, a history of stem cell transplant, immunodeficiency, and/or a medical or psychiatric illness (that in the investigator's opinion, would prevent adequate compliance with study therapy or evaluation of the endpoints)

Sites / Locations

  • Southern Illinois University School of Medicine
  • Great Lakes Cancer Institute Breslin Cancer Center
  • The Methodist Hospital

Outcomes

Primary Outcome Measures

Safety
Tolerability
Anti-tumor Activity

Secondary Outcome Measures

Full Information

First Posted
May 22, 2006
Last Updated
March 8, 2012
Sponsor
Endocyte
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1. Study Identification

Unique Protocol Identification Number
NCT00329368
Brief Title
Safety and Tolerability Study of FolateImmune in Combination With Cytokines in Patients With Refractory or Metastatic Cancer
Official Title
A Phase I Study of EC90 With GPI-0100 Adjuvant Followed by EC17 With Cytokines (Interleukin-2 [IL-2] and Interferon-alpha [IFN-alpha]) in Patients With Refractory or Metastatic Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
June 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Endocyte

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a Phase 1b clinical trial to assess the safety and tolerability of vaccination with EC90 (KLH-FITC) and GPI-0100 (adjuvant) followed by treatment with EC17 (Folate-FITC) in combination with low-dose cytokines (IL-2 and IFN-alpha) in patients with metastatic or refractory cancer.
Detailed Description
Rationale: This is a Phase 1b, single-cohort study of FolateImmune in combination with low-doses of the cytokines Interleukin-2 (IL-2) and Interferon-alpha (IFN-alpha). FolateImmune treatment consists of subcutaneous vaccinations with EC90, a compound designed to elicit an immune response (antibodies) to a dye called fluorescein (FITC), in combination with GPI-0100 adjuvant (a drug intended to improve antibody production). Vaccination is followed by treatment with EC17, a drug made by linking folate (a vitamin) with FITC. Experimental evidence has shown that the folate vitamin receptor is over-expressed in many human cancers. It is expected that EC17 will attach to cancer cells through the folate vitamin receptor and that antibodies to FITC will recognize the cancer cell and mark it for destruction by the body's immune system. Two drugs, IL-2 and IFN-alpha, will be administered at low doses in combination with EC17 in order to boost the immune response. Objectives: Evaluate the safety of administering EC90 vaccine with GPI-0100 adjuvant. Evaluate the safety of administering EC17 concurrent with IL-2 and IFN-alpha

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer
Keywords
Cancer, Vaccine, Phase I, FolateImmune, Recurrent, Refractory, Experimental

7. Study Design

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

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
EC90 (KLH-FITC)
Other Intervention Name(s)
Keyhole limpet hemocyanin fluorescein
Intervention Description
1.2mg in combination with adjuvant GPI-0100 administered subcutaneously, weekly for 4 consecutive weeks during the first treatment cycle, weekly for 2 consecutive weeks during the second cycle and once for each additional cycle.
Intervention Type
Biological
Intervention Name(s)
GPI-0100
Other Intervention Name(s)
Saponin-based adjuvant
Intervention Description
3.0mg in combination with EC90 administered subcutaneously weekly for 4 consecutive weeks during the first treatment cycle, weekly for 2 consecutive weeks during the second cycle and once for each additional cycle.
Intervention Type
Drug
Intervention Name(s)
EC17 (Folate-FITC)
Other Intervention Name(s)
folate-fluorescein conjugate, folate-hapten conjugate
Intervention Description
0.3mg/kg administered subcutaneously 5 days per week (Monday through Friday) for 4 consecutive weeks followed by 2 observation weeks for each cycle.
Intervention Type
Drug
Intervention Name(s)
Interleukin-2
Other Intervention Name(s)
IL-2, Proleukin
Intervention Description
Low dose (7-12 MIU) IL-2 administered subcutaneously three times per week (MWF) for 3 consecutive weeks during the first cycle, 4 consecutive weeks during cycle 2 and additional cycles
Intervention Type
Drug
Intervention Name(s)
Interferon-alpha
Other Intervention Name(s)
IFN-alpha, Intron-A
Intervention Description
3.0 MIU administered subcutaneously 3 times per week (MWF) for 3 consecutive weeks during the first cycle of treatment, then 3.0 MIU administered subcutaneously 3 times per week (MWF) for 4 weeks for cycle 2 and additional cycles.
Primary Outcome Measure Information:
Title
Safety
Time Frame
Initial dose of study therapy through 30 days post last dose of study therapy
Title
Tolerability
Time Frame
Initial dose of study therapy through 30 days post last dose of study therapy
Title
Anti-tumor Activity
Time Frame
From initial dose of study therapy to disease progression

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Have a histologically confirmed diagnosis of metastatic or refractory cancer for which there are no effective standard therapeutic options available, (Note: for patients accrued at Southern Illinois University, a diagnosis of renal (i.e., kidney) carcinoma is required.) Have signed an Institutional Review Board (IRB) approved informed consent form (ICF) prior to performing any study evaluation/procedures Be > or = 18 years of age and women must either be 1) not of childbearing potential or 2) have a negative serum pregnancy test within 7 days prior to commencing treatment. Patients are considered not of childbearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or they are postmenopausal (12 consecutive months of amenorrhea [lack of menstruation]) (If applicable) Have completed prior cytotoxic chemotherapy, radiotherapy or immunotherapy or experimental therapy > or = 30 days prior to the study enrollment, and recovered form associated toxicities Have an Eastern Cooperative Oncology Group (ECOG) score of < or = 2, and an anticipated life expectancy of at least 6 months Have adequate hematologic function, as defined by an absolute or calculated neutrophil count > or = 1500/microL, platelet count > or = 100000/microL, lymphocyte count > or = 500/microL, and hemoglobin level > or = 10 g/dL. Patients may not receive prophylactic transfusion in order to qualify for trial eligibility Have adequate renal function, as defined by a documented serum creatinine of < or = 2.0mg/dL. Greater than "1+" proteinuria will require microscope evaluation and the results discussed with the medical monitor prior to patient enrollment; or if serum creatine is >2.0, patient must have an actual or calculated 24-hour creatinine clearance of >60mL/min and no obvious evidence of concurrent medullary cystic disease or obstructive uropathy Have adequate hepatic function, as defined by a total bilirubin level < or = 1.5 x upper limit of normal (ULN) and alkaline phosphatase, aspartate transaminase (AST), and alanine transaminase (ALT) levels < or = 2.5 x ULN. If alkaline phosphatase is outside of these parameters and is due to bone metastases (as verified by the assessment of isoenzymes), then the patient is eligible. Exclusion Criteria: Have previously participated in a FolateImmune trial Have a history of severe hypersensitivity (grade 3 - 4 allergic reaction) to fluorescein or any drug, radiologic contrast agent, insect bite, food, cytokines, or any other agent; or have received fluorescein within 30 days of the study. Have medical conditions that preclude the use of IL-2 or IFN-alpha. These conditions include but are not limited to, diabetes mellitus with a history of progression to diabetic ketoacidosis, history of severe coagulation disorder, psoriasis, sarcoidosis, retinal hemorrhage, symptomatic pulmonary disease, heart failure (> or = New York Heart Association NYHA class II), or transplant requiring immunosuppressive therapy Be pregnant or breast-feeding Be currently receiving an experimental drug, or used an experimental device within 30 days of study entry Be currently undergoing chemotherapy, anticancer hormonal therapy, and/or therapy with immunosuppressant agents Have any concomitant malignancy with the exception of basal cell or squamous cell carcinoma of skin Have radiographically documented evidence of current brain metastases, a history of stem cell transplant, immunodeficiency, and/or a medical or psychiatric illness (that in the investigator's opinion, would prevent adequate compliance with study therapy or evaluation of the endpoints)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard A Messmann, MD, MHS, BSc
Organizational Affiliation
Endocyte
Official's Role
Study Director
Facility Information:
Facility Name
Southern Illinois University School of Medicine
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62794
Country
United States
Facility Name
Great Lakes Cancer Institute Breslin Cancer Center
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48910
Country
United States
Facility Name
The Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Safety and Tolerability Study of FolateImmune in Combination With Cytokines in Patients With Refractory or Metastatic Cancer

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