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

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:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Endocyte:

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 (Adult, Senior)
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

Endocyte

More Information

Publications:

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.


Responsible Party:	Endocyte
ClinicalTrials.gov Identifier:	NCT00308269 History of Changes
Other Study ID Numbers:	8109-006 EC-FV-01
Study First Received:	March 27, 2006
Last Updated:	December 18, 2014
Health Authority:	United States: Food and Drug Administration

Keywords provided by Endocyte:


Cancer Phase I EC145 Recurrent	Refractory Solid Tumors Experimental

Additional relevant MeSH terms:


Folic Acid Vinca Alkaloids Hematinics Vitamin B Complex Vitamins Micronutrients Growth Substances	Physiological Effects of Drugs Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 27, 2016