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

Sponsor

Endocyte (Industry)

Overall Status

Completed

CT.gov ID

NCT00329368

Collaborator

(none)

Enrollment

Locations

Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Biological: EC90 (KLH-FITC) Biological: GPI-0100 Drug: EC17 (Folate-FITC) Drug: Interleukin-2 Drug: Interferon-alpha	Phase 1

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

Study Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Sep 1, 2005

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Jun 1, 2008

Outcome Measures

Primary Outcome Measures

Safety [Initial dose of study therapy through 30 days post last dose of study therapy]
Tolerability [Initial dose of study therapy through 30 days post last dose of study therapy]
Anti-tumor Activity [From initial dose of study therapy to disease progression]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62794
2	Great Lakes Cancer Institute Breslin Cancer Center	Lansing	Michigan	United States	48910
3	The Methodist Hospital	Houston	Texas	United States	77030