Study of Vintafolide (MK-8109, EC145) for the Treatment of Recurrent or Refractory Solid Tumors (MK-8109-006, EC-FV-01)

• Safety
• Tolerability
• Maximum tolerated dose (MTD)

• Number of Participants with Best Overall Tumor Response: Participants with Folate Receptor Positive Tumors at Baseline [ Time Frame: Up to Week 24 ]
  Tumor status was assessed according to Response Evaluation Criteria in Solid Tumors. Tumor responses used as a reference the sum of the longest diameter (LD) of the target lesions using imaging studies. Partial Response was defined as ≥30% decrease in LD. Stable Disease was defined as neither sufficient shrinkage or increase in LD to qualify as either Partial Response or Progressive Disease. Progressive Disease was defined as ≥20% increase in LD.
• Number of Participants with a Dose-Limiting Toxiciity During Cycle 1 Treatment [ Time Frame: Up to Day 26 in Treatment Cycle 1 ]
  Dose limiting toxicity was defined as an adverse event that is likely related to the study medication, and fulfills any one of the following criteria: Grade 2 non-hematological toxicity that fails to recover to a Grade 1 level or Baseline at the time that the next treatment cycle is due (with the exception of alopecia); Grade 3 non-hematological toxicity (except for nausea/vomiting without maximal symptomatic / prophylactic treatment); Grade 4 hematological toxicity; Toxicity that, in the opinion of the investigator, would prevent use of the drug dose or regimen by the general oncology community.
• Number of Participants with an Adverse Event Leading to Study Discontinuation During Cycle 1 Treatment [ Time Frame: Up to Day 26 in Treatment Cycle 1 ]
  An adverse event was defined as any untoward, undesired, or unplanned clinical event in the form of physical signs, symptoms, disease, laboratory or physiological observations in a participant administered the Sponsor's product whether or not related to the use of the product
• Number of Participants with Best Overall Tumor Response: All Treated Participants [ Time Frame: Up to Week 24 ]
  Tumor status was assessed according to Response Evaluation Criteria in Solid Tumors. Tumor responses used as a reference the sum of the longest diameter (LD) of the target lesions using imaging studies. Complete Response was defined as disappearance of all target lesions. Partial Response was defined as ≥30% decrease in LD. Stable Disease was defined as neither sufficient shrinkage or increase in LD to qualify as either Partial Response or Progressive Disease. Progressive Disease was defined as ≥20% increase in LD.
• Maximum Plasma Concentration (Cmax) of Vintafolide on Day 1 of Treatment Cycle 1 [ Time Frame: Up to 90 minutes after IV bolus dosing and up to 60 minutes after the start of the 1-hour IV infusion on Day 1 of treatment cycle 1 ]
  Blood was collected from participants for determination of plasma vintafolide. The lower limit of quantitation for vintafolide was 10 ng/mL.
• Maximum Plasma Concentration (Cmax) of Vintafolide on Day 3 of Treatment Cycle 1 [ Time Frame: Up to 90 minutes after IV bolus dosing and up to 60 minutes after the start of the 1-hour IV infusion on Day 3 of treatment cycle 1 ]
  Blood was collected from participants for determination of plasma vintafolide. The lower limit of quantitation for vintafolide was 10 ng/mL.
• Area Under the Plasma Concentration-Time Curve (AUC) of Vintafolide on Day 1 of Treatment Cycle 1 [ Time Frame: Up to 90 minutes after IV bolus dosing and up to 60 minutes after the start of the 1-hour IV infusion on Day 1 of treatment cycle 1 ]
  Blood was collected from participants for determination of plasma vintafolide. The lower limit of quantitation for vintafolide was 10 ng/mL.
• Area Under the Plasma Concentration-Time Curve (AUC) of Vintafolide on Day 3 of Treatment Cycle 1 [ Time Frame: Up to 90 minutes after IV bolus dosing and up to 60 minutes after the start of the 1-hour IV infusion on Day 3 of treatment cycle 1 ]
  Blood was collected from participants for determination of plasma vintafolide. The lower limit of quantitation for vintafolide was 10 ng/mL.

• Drug: Vintafolide IV Bolus
  Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate
• Drug: Vintafolide IV Infusion
  Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate

• Experimental: Vintafolide 1.2 mg IV Bolus
  Vintafolide 1.2 mg administered by IV bolus on Days 1, 3, 5, 15, 17, and 19 of 4-week treatment cycles
  Intervention: Drug: Vintafolide IV Bolus
• Experimental: Vintafolide 2.5 mg IV Bolus
  Vintafolide 2.5 mg administered by IV bolus on Days 1, 3, 5, 15, 17, and 19 of 4-week treatment cycles
  Intervention: Drug: Vintafolide IV Bolus
• Experimental: Vintafolide 4.0 mg IV Bolus
  Vintafolide 4.0 mg administered by IV bolus on Days 1, 3, 5, 15, 17, and 19 of 4-week treatment cycles
  Intervention: Drug: Vintafolide IV Bolus
• Experimental: Vintafolide 2.5 mg IV Infusion
  Vintafolide 2.5 mg administered by a 1-hour IV infusion on Days 1, 3, 5, 15, 17, and 19 of 4-week treatment cycles
  Intervention: Drug: Vintafolide IV Infusion
• Experimental: Vintafolide 3.0 mg IV Infusion
  Vintafolide 3.0 mg administered by a 1-hour IV infusion on Days 1, 3, 5, 15, 17, and 19 of 4-week treatment cycles
  Intervention: Drug: Vintafolide IV Infusion

• Li J, Sausville EA, Klein PJ, Morgenstern D, Leamon CP, Messmann RA, LoRusso P. Clinical pharmacokinetics and exposure-toxicity relationship of a folate-Vinca alkaloid conjugate EC145 in cancer patients. J Clin Pharmacol. 2009 Dec;49(12):1467-76. doi: 10.1177/0091270009339740. Epub 2009 Oct 16.
• Lorusso PM, Edelman MJ, Bever SL, Forman KM, Pilat M, Quinn MF, Li J, Heath EI, Malburg LM, Klein PJ, Leamon CP, Messmann RA, Sausville EA. Phase I study of folate conjugate EC145 (Vintafolide) in patients with refractory solid tumors. J Clin Oncol. 2012 Nov 10;30(32):4011-6. doi: 10.1200/JCO.2011.41.4946. Epub 2012 Oct 1.

Inclusion Criteria:

• Histological or cytological diagnosis of neoplasm
• No effective standard therapeutic options
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• >=4 weeks post therapeutic radiation of chemotherapy >=6 weeks for nitrosoureas and mitomycin C) and recovery from associated toxicities
• Negative serum pregnancy test for women of child-bearing potential and willingness to practice contraceptive methods
• Adequate bone marrow reserve, renal, and hepatic function

Exclusion Criteria:

• Concurrent hematological malignancies
• Women who are pregnant or lactating
• Evidence of symptomatic brain metastases
• Receiving concomitant anticancer therapy (excluding supportive care)
• Requires palliative radiotherapy at time of study entry