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
  Purpose

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.


Condition Intervention Phase
Cancer
Drug: Vintafolide IV Bolus
Drug: Vintafolide IV Infusion
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Protocol EC-FV-01: A Phase 1 Study of EC145 Administered in Weeks 1 and 3 of a 4-Week Cycle

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 32
Study Start Date: March 2006
Study Completion Date: July 2008
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Vintafolide IV Bolus
Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate
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
Drug: Vintafolide IV Bolus
Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate
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
Drug: Vintafolide IV Bolus
Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate
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
Drug: Vintafolide IV Infusion
Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate
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
Drug: Vintafolide IV Infusion
Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00308269

Locations
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Endocyte
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00308269     History of Changes
Other Study ID Numbers: 8109-006, EC-FV-01
Study First Received: March 27, 2006
Last Updated: May 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Cancer
Phase I
EC145
Recurrent
Refractory
Solid Tumors
Experimental

Additional relevant MeSH terms:
Folic Acid
Vinca Alkaloids
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 22, 2014