Clinical trial NCT00308269: Study of Vintafolide (MK-8109, EC145) for the Treatment of Recurrent or Refractory Solid Tumors (MK-8109-006, EC-FV-01)
Official title: Protocol EC-FV-01: A Phase 1 Study of EC145 Administered in Weeks 1 and 3 of a 4-Week Cycle
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: Cancer
Phase I
EC145
Recurrent
Refractory
Solid Tumors
Experimental
Lead sponsor: Endocyte
Sponsor class: INDUSTRY
First posted: 2006-03-29
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Maximum Tolerated Dose During Cycle 1 Treatment
timeFrame: Up to Day 26 in Treatment Cycle 1
Secondary outcomes:
measure: Number of Participants with Best Overall Tumor Response: Participants with Folate Receptor Positive Tumors at Baseline
timeFrame: Up to Week 24
measure: Number of Participants with a Dose-Limiting Toxiciity During Cycle 1 Treatment
timeFrame: Up to Day 26 in Treatment Cycle 1
measure: Number of Participants with an Adverse Event Leading to Study Discontinuation During Cycle 1 Treatment
timeFrame: Up to Day 26 in Treatment Cycle 1
measure: Number of Participants with Best Overall Tumor Response: All Treated Participants
timeFrame: Up to Week 24
measure: Maximum Plasma Concentration (Cmax) of Vintafolide on Day 1 of Treatment Cycle 1
timeFrame: 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
measure: Maximum Plasma Concentration (Cmax) of Vintafolide on Day 3 of Treatment Cycle 1
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve (AUC) of Vintafolide on Day 1 of Treatment Cycle 1
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve (AUC) of Vintafolide on Day 3 of Treatment Cycle 1
timeFrame: 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
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
References:
citation: 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.
citation: 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.