A Phase II Study of EC17 (Folate-hapten Conjugate) in Patients With Progressive Metastatic Renal Cell Carcinoma

This study has been terminated.
(Changes in treatment paradigm resulted in a lower than expected rate of accrual.)
Sponsor:
Information provided by (Responsible Party):
Endocyte
ClinicalTrials.gov Identifier:
NCT00485563
First received: June 11, 2007
Last updated: March 5, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Renal Cell Carcinoma
Biological: EC90 (KLH-FITC)
Biological: GPI-0100
Drug: EC17 (Folate-FITC)
Drug: Interleukin-2
Drug: Interferon-alpha
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of EC17 (Folate-hapten Conjugate) in Patients With Progressive Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Endocyte:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the safety and tolerability of folate-hapten conjugate therapy [ Time Frame: Duration of study drug administration + 30 days ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • To assess the safety and tolerability of 99mTc-EC20 [ Time Frame: Duration of study drug administration + 7 days ] [ Designated as safety issue: Yes ]

Enrollment: 12
Study Start Date: June 2007
Study Completion Date: March 2009
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: EC90 (KLH-FITC)
    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.
    Other Name: Keyhole limpet hemocyanin fluorescein
    Biological: GPI-0100
    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.
    Other Name: Saponin-based adjuvant
    Drug: EC17 (Folate-FITC)
    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.
    Other Names:
    • folate-fluorescein conjugate;
    • folate-hapten conjugate
    Drug: Interleukin-2
    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.
    Other Names:
    • IL-2
    • Proleukin
    Drug: Interferon-alpha
    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.
    Other Names:
    • IFN-alpha
    • Intron-A
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00485563

Locations
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-7680
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, Texas
The Methodist Hospital Research Institute
Houston, Texas, United States, 77030
Sponsors and Collaborators
Endocyte
Investigators
Study Director: Richard A Messmann, MD, MHS, BSc Endocyte
  More Information

No publications provided

Responsible Party: Endocyte
ClinicalTrials.gov Identifier: NCT00485563     History of Changes
Other Study ID Numbers: EC-FI-004
Study First Received: June 11, 2007
Last Updated: March 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Endocyte:
Cancer
Vaccine
Phase 2
folate-hapten conjugate
Progressive
Metastatic
Experimental

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Interferon-alpha
Interferon Alfa-2a
Interferons
Keyhole-limpet hemocyanin
Interleukin-2
Folic Acid
Vitamin B Complex
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 28, 2014