Back to resultsA Phase II Study of EC17 (Folate-hapten Conjugate) in Patients With Progressive Metastatic Renal Cell Carcinoma
Primary Purpose
Renal Cell Carcinoma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
EC90 (KLH-FITC)
GPI-0100
EC17 (Folate-FITC)
Interleukin-2
Interferon-alpha
Sponsored by
About this trial
This is an interventional treatment trial for Renal Cell Carcinoma focused on measuring Cancer, Vaccine, Phase 2, folate-hapten conjugate, Progressive, Metastatic, Experimental
Eligibility Criteria
Inclusion Criteria:
- Must have a histologically confirmed diagnosis of renal cell carcinoma (clear cell or predominately clear cell component). Papillary histology may also be enrolled (maximum of 6 patients)
- Must be diagnosed with relapsed or Stage IV disease that is medically or surgically unresectable and that has progressed after systemic therapy, including at least one agent in the general class of kinase inhibitors (TKI not required for papillary histology)
- Must have measurable/evaluable metastatic disease sites that have not previously received radiotherapy and which does not require palliative intervention (at the time of enrollment). Patients with non-measurable/evaluable disease are ineligible
- Must have at least one tumor lesion that displays uptake of 99mTc-EC20
- Must be > than or = 18 years of age
- Women must either be 1)not of child-bearing potential of 2)have a negative serum pregnancy test within 7 days prior to commencing treatment with investigational agents
- Must have completed prior cytotoxic chemotherapy, radiotherapy, immunotherapy or experimental therapy 30 or more days prior to study enrollment, and recovered (or returned to baseline) from associated acute toxicities. This restriction excludes palliative radiotherapy.
- Must have an ECOG score less than or equal to 2
- Must have adequate hematologic, renal, and heptic function
Exclusion Criteria:
- Must not have a history of severe hypersensitivity (grade 3 - 4 allergic reaction) to fluorescein, radiological contrast agent, cytokines, or have received fluorescein within 30 days of the study
- Must not have medical conditions that preclude the use of IL-2 or IFN-α.
- Must not be pregnant or breast-feeding
- Must not be currently undergoing chemotherapy, anticancer hormonal therapy, and/or therapy with immunosuppressant agents
- Must not be currently receiving bisphosphonates such as Zometa® (unless started > four weeks prior to treatment with EC90/GPI-0100, in which case they can be continued)
- Must not have any concomitant malignancy with the exception of basal cell or squamous cell carcinoma of skin
- Must not 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)
- Must not have been administered another radiopharmaceutical that would interfere with the assessment of 99mTc-EC20
- Must not be unable to tolerate conditions for radionuclide imaging
Sites / Locations
- University of Nebraska Medical Center
- Hackensack University Medical Center
- The Methodist Hospital Research Institute
Outcomes
Primary Outcome Measures
Response Rate - the proportion of subjects with objective response based on RECIST criteria
Secondary Outcome Measures
To assess the safety and tolerability of folate-hapten conjugate therapy
Time-to-progression, response duration, overall survival time observed after folate-hapten conjugate therapy and ECOG performance status
To assess the safety and tolerability of 99mTc-EC20
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00485563
Brief Title
A Phase II Study of EC17 (Folate-hapten Conjugate) in Patients With Progressive Metastatic Renal Cell Carcinoma
Official Title
A Phase II Study of EC17 (Folate-hapten Conjugate) in Patients With Progressive Metastatic Renal Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2012
Overall Recruitment Status
Terminated
Why Stopped
Changes in treatment paradigm resulted in a lower than expected rate of accrual.
Study Start Date
June 2007 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
March 2009 (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 2 clinical trial to collect data on tumor responses produced by folate-hapten conjugate therapy (vaccination with EC90 [KLH-FITC] and GPI-0100 adjuvant followed by treatment with EC17 (folate-FITC) in combination with low-dose cytokines in patients with progressive metastatic renal cell carcinoma. All patients will undergo imaging with the investigational imaging agent 99mTc-EC20 (FolateScan) during the screening period to confirm eligibility for the treatment portion of the clinical trial.
Detailed Description
Rationale: This is a Phase 2 study of folate-hapten conjugate therapy in combination with low-doses of the cytokines Interleukin-2 (IL-2) and Interferon-alpha (INF-alpha). Folate-hapten conjugate 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 receptor is over-expressed in many human cancers, including renal cell carcinoma. It is expected that EC17 will attach to cancer cells through the folate 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. During the screening period, all potential patients will undergo imaging with 99mTc-EC20 (a technetium-based, folate- linked radiopharmaceutical [EC20]) for the purpose of identifying patients whose tumors express the folate receptor; the target of folate-hapten conjugate therapy. Prior to receiving EC90/GPI-0100 and EC17 therapy, patients must exhibit at least one tumor lesion that displays adequate uptake of 99mTc-EC20 during the imaging procedure.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Cell Carcinoma
Keywords
Cancer, Vaccine, Phase 2, folate-hapten conjugate, Progressive, Metastatic, Experimental
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (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 (beneath the skin) weekly for 4 consecutive weeks during the first cycle of treatment, 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
3.0 mg in combination with EC90 administered subcutaneously weekly for 4 consecutive weeks during the first cycle of treatment, 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 for the first two treatment cycles and then 3 days per week (Monday, Wednesday, Friday) for 3 consecutive weeks for each additional cycle.
Intervention Type
Drug
Intervention Name(s)
Interleukin-2
Other Intervention Name(s)
IL-2, Proleukin
Intervention Description
7.0 MIU administered subcutaneously 3 times per week (Monday, Wednesday, Friday) for 4 consecutive weeks during the first 2 cycles of treatment, then 2.5 MIU administered subcutaneously 3 times per week (Monday, Wednesday, Friday) for 3 consecutive weeks for each additional cycle.
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 (Monday, Wednesday, Friday) for 4 consecutive weeks during the first 2 cycles of treatment, then 3.0 MIU administered subcutaneously 3 times per week (Monday, Wednesday, Friday) for 3 consecutive weeks for each additional cycle.
Primary Outcome Measure Information:
Title
Response Rate - the proportion of subjects with objective response based on RECIST criteria
Time Frame
A minimum of 13 weeks (time to first follow-up CT)
Secondary Outcome Measure Information:
Title
To assess the safety and tolerability of folate-hapten conjugate therapy
Time Frame
Duration of study drug administration + 30 days
Title
Time-to-progression, response duration, overall survival time observed after folate-hapten conjugate therapy and ECOG performance status
Time Frame
Up to 2 years following completion of therapy
Title
To assess the safety and tolerability of 99mTc-EC20
Time Frame
Duration of study drug administration + 7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Must have a histologically confirmed diagnosis of renal cell carcinoma (clear cell or predominately clear cell component). Papillary histology may also be enrolled (maximum of 6 patients)
Must be diagnosed with relapsed or Stage IV disease that is medically or surgically unresectable and that has progressed after systemic therapy, including at least one agent in the general class of kinase inhibitors (TKI not required for papillary histology)
Must have measurable/evaluable metastatic disease sites that have not previously received radiotherapy and which does not require palliative intervention (at the time of enrollment). Patients with non-measurable/evaluable disease are ineligible
Must have at least one tumor lesion that displays uptake of 99mTc-EC20
Must be > than or = 18 years of age
Women must either be 1)not of child-bearing potential of 2)have a negative serum pregnancy test within 7 days prior to commencing treatment with investigational agents
Must have completed prior cytotoxic chemotherapy, radiotherapy, immunotherapy or experimental therapy 30 or more days prior to study enrollment, and recovered (or returned to baseline) from associated acute toxicities. This restriction excludes palliative radiotherapy.
Must have an ECOG score less than or equal to 2
Must have adequate hematologic, renal, and heptic function
Exclusion Criteria:
Must not have a history of severe hypersensitivity (grade 3 - 4 allergic reaction) to fluorescein, radiological contrast agent, cytokines, or have received fluorescein within 30 days of the study
Must not have medical conditions that preclude the use of IL-2 or IFN-α.
Must not be pregnant or breast-feeding
Must not be currently undergoing chemotherapy, anticancer hormonal therapy, and/or therapy with immunosuppressant agents
Must not be currently receiving bisphosphonates such as Zometa® (unless started > four weeks prior to treatment with EC90/GPI-0100, in which case they can be continued)
Must not have any concomitant malignancy with the exception of basal cell or squamous cell carcinoma of skin
Must not 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)
Must not have been administered another radiopharmaceutical that would interfere with the assessment of 99mTc-EC20
Must not be unable to tolerate conditions for radionuclide imaging
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
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-7680
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
The Methodist Hospital Research Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Phase II Study of EC17 (Folate-hapten Conjugate) in Patients With Progressive Metastatic Renal Cell Carcinoma
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