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

This study has been completed.
Sponsor:
Collaborator:
Endocyte
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00308269
First received: March 27, 2006
Last updated: May 21, 2014
Last verified: May 2014

March 27, 2006
May 21, 2014
March 2006
August 2007   (final data collection date for primary outcome measure)
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.
  • Maximum tolerated dose (MTD)
  • Safety
  • Tolerability
Complete list of historical versions of study NCT00308269 on ClinicalTrials.gov Archive Site
  • 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.
Pharmacokinetic and pharmacodynamic parameters; Anti-tumor activity; Feasibility of regimen
Not Provided
Not Provided
 
Study of Vintafolide (MK-8109, EC145) for the Treatment of Recurrent or Refractory Solid Tumors (MK-8109-006, EC-FV-01)
Protocol EC-FV-01: A Phase 1 Study of EC145 Administered in Weeks 1 and 3 of a 4-Week Cycle

This is a Phase I clinical trial evaluating the safety and tolerability of escalating doses of vintafolide (EC145) in participants with relapsed or refractory advanced tumors. The primary objective of this study is to determine the safety and maximum tolerated dose of vintafolide given by intravenous bolus or infusion. The efficacy of the treatment will also be measured.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Cancer
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
32
July 2008
August 2007   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00308269
8109-006, EC-FV-01
No
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Endocyte
Not Provided
Merck Sharp & Dohme Corp.
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP