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

• Maximum Tolerated Dose During Cycle 1 Treatment [ Time Frame: Up to Day 26 in Treatment Cycle 1 ] [ Designated as safety issue: Yes ]
  Maximum Tolerated Dose (MTD) was defined as the highest dose that can safely be administered to a patient to produce acceptable, manageable and reversible toxicity. This level was further defined as the dose level at which no more than 1 of 6 participants had dose-limiting toxicity (DLT) and the level below the dose at which ≥2 of 6 participants had DLT.
  
  

• Number of Participants with Best Overall Tumor Response: Participants with Folate Receptor Positive Tumors at Baseline [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: Yes ]
  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 ] [ Designated as safety issue: Yes ]
  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 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  Blood was collected from participants for determination of plasma vintafolide. The lower limit of quantitation for vintafolide was 10 ng/mL.
  
  

This is a dose escalation study of vintafolide administered by intravenous (IV) bolus or infusion during weeks 1 and 3 of a 4-week cycle to participants with solid tumors refractory to current therapies. Vintafolide is a drug that is specifically designed to enter cells via a folate vitamin receptor. Experimental evidence shows that the target receptor is over-expressed in many human cancers. There are no previous human studies of vintafolide treatment; however, lab research (research in test tubes and/or animals) using vintafolide has shown activity against tumors in animals. This activity in animal models suggests that vintafolide may be useful as chemotherapy against human cancers.