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

• 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 ]
  

• 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 ]
  

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

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.