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

Tracking Information
First Submitted Date ICMJE	March 27, 2006
First Posted Date ICMJE	March 29, 2006
Last Update Posted Date	December 19, 2014
Study Start Date ICMJE	March 2006
Actual Primary Completion Date	August 2007 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 21, 2014)	Maximum Tolerated Dose During Cycle 1 Treatment [ Time Frame: Up to Day 26 in Treatment Cycle 1 ]; 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.
Original Primary Outcome Measures ICMJE; (submitted: March 27, 2006)	Safety; Tolerability; Maximum tolerated dose (MTD)
Change History	Complete list of historical versions of study NCT00308269 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: May 21, 2014)	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.
Original Secondary Outcome Measures ICMJE; (submitted: March 27, 2006)	Pharmacokinetic and pharmacodynamic parameters; Anti-tumor activity; Feasibility of regimen
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Study of Vintafolide (MK-8109, EC145) for the Treatment of Recurrent or Refractory Solid Tumors (MK-8109-006, EC-FV-01)
Official Title ICMJE	Protocol EC-FV-01: A Phase 1 Study of EC145 Administered in Weeks 1 and 3 of a 4-Week Cycle
Brief Summary	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.
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.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Cancer
Intervention ICMJE	Drug: Vintafolide IV Bolus Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate; Drug: Vintafolide IV Infusion Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate
Study Arms	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
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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: September 30, 2008)	32
Original Enrollment ICMJE; (submitted: March 27, 2006)	30
Actual Study Completion Date	July 2008
Actual Primary Completion Date	August 2007 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00308269
Other Study ID Numbers ICMJE	8109-006; EC-FV-01 ( Other Identifier: Endocyte )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Endocyte
Study Sponsor ICMJE	Endocyte
Collaborators ICMJE	Not Provided
Investigators ICMJE	Not Provided
PRS Account	Endocyte
Verification Date	December 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP