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

NCT00308269 | Completed Phase 1

• 2 other identifiers: 8109-006EC-FV-01
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

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.

Conditions

Cancer

Keywords

Cancer; Phase I; EC145; Recurrent; Refractory; Solid Tumors; Experimental

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose During Cycle 1 Treatment

  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.

  Up to Day 26 in Treatment Cycle 1

Secondary Outcomes (8)

• Number of Participants with Best Overall Tumor Response: Participants with Folate Receptor Positive Tumors at Baseline

  Up to Week 24

• Number of Participants with a Dose-Limiting Toxiciity During Cycle 1 Treatment

  Up to Day 26 in Treatment Cycle 1

• Number of Participants with an Adverse Event Leading to Study Discontinuation During Cycle 1 Treatment

  Up to Day 26 in Treatment Cycle 1

• Number of Participants with Best Overall Tumor Response: All Treated Participants

  Up to Week 24

• Maximum Plasma Concentration (Cmax) of Vintafolide on Day 1 of Treatment Cycle 1

  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

Study Arms (5)

Vintafolide 1.2 mg IV Bolus

EXPERIMENTAL

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 2.5 mg IV Bolus

EXPERIMENTAL

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 4.0 mg IV Bolus

EXPERIMENTAL

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 2.5 mg IV Infusion

EXPERIMENTAL

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 3.0 mg IV Infusion

EXPERIMENTAL

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

Interventions

Vintafolide IV Bolus DRUG

Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate

Vintafolide 1.2 mg IV Bolus; Vintafolide 2.5 mg IV Bolus; Vintafolide 4.0 mg IV Bolus

Vintafolide IV Infusion DRUG

Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate

Vintafolide 2.5 mg IV Infusion; Vintafolide 3.0 mg IV Infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Endocyte: lead

Study Sites (2)

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Related Publications (2)

• 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.

  PMID: 19837906 RESULT

• 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.

  PMID: 23032618 RESULT

MeSH Terms

Conditions

Neoplasms; Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2006
• First Posted: March 29, 2006
• Study Start: March 1, 2006
• Primary Completion: August 1, 2007
• Study Completion: July 1, 2008
• Last Updated: December 19, 2014

Record last verified: 2014-12

Locations

US (2)