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

Cancer Clinical Trial

Official title:

Protocol EC-FV-01: A Phase 1 Study of EC145 Administered in Weeks 1 and 3 of a 4-Week Cycle

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00308269
• Other study ID #: 8109-006
• Secondary ID: EC-FV-01
• Status: Completed
• Phase: Phase 1
• First received: March 27, 2006
• Last updated: December 18, 2014
• Start date: March 2006
• Est. completion date: July 2008

Study information

• Verified date: December 2014
• Source: Endocyte
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: July 2008
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• Vintafolide IV Bolus
Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate
• Vintafolide IV Infusion
Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate

Locations

Country	Name	City	State
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Endocyte

Country where clinical trial is conducted

United States, 

References & 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. — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Number of Participants with Best Overall Tumor Response: Participants with Folate Receptor Positive Tumors at Baseline	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.	Up to Week 24	No
Secondary	Number of Participants with a Dose-Limiting Toxiciity During Cycle 1 Treatment	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.	Up to Day 26 in Treatment Cycle 1	Yes
Secondary	Number of Participants with an Adverse Event Leading to Study Discontinuation During Cycle 1 Treatment	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	Up to Day 26 in Treatment Cycle 1	Yes
Secondary	Number of Participants with Best Overall Tumor Response: All Treated Participants	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.	Up to Week 24	No
Secondary	Maximum Plasma Concentration (Cmax) of Vintafolide 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.	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	No
Secondary	Maximum Plasma Concentration (Cmax) of Vintafolide 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.	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	No
Secondary	Area Under the Plasma Concentration-Time Curve (AUC) of Vintafolide 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.	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	No
Secondary	Area Under the Plasma Concentration-Time Curve (AUC) of Vintafolide 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.	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	No