CancerPhase 1NCT00308269
Study of Vintafolide (MK-8109, EC145) for the Treatment of Recurrent or Refractory Solid Tumors (MK-8109-006, EC-FV-01)
A Phase 1 study testing Vintafolide IV Bolus and Vintafolide IV Infusion in people with Cancer, run by Endocyte at 2 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- Vintafolide IV Bolus and Vintafolide IV Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2006to Jul 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, 21201
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
About this study
Official title: Protocol EC-FV-01: A Phase 1 Study of EC145 Administered in Weeks 1 and 3 of a 4-Week Cycle
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.
Read the 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.
- Conditions
- Cancer
- Being tested
- Vintafolide IV Bolus, Vintafolide IV Infusion
- Keywords
- Cancer, Phase I, EC145, Recurrent, Refractory, Solid Tumors, Experimental
- Medical subject headings
- Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vintafolide IV BolusDrug
Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate
Vintafolide IV InfusionDrug
Vintafolide is a folic acid desacetylvinblastine hydrazide conjugate
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Vintafolide IV Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: Up to Week 24
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.
Measured: Up to Day 26 in Treatment Cycle 1
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
Measured: Up to Day 26 in Treatment Cycle 1
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.
Measured: Up to Week 24
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2006 (estimated)
- Study startMar 2006
- Primary completionAug 2007
- Study completionJul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Endocyte
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00308269
- Sponsor's protocol ID
- 8109-006
- Other IDs
- EC-FV-01
- Status last verified
- Dec 2014
- First submitted
- 27 Mar 2006
- Last updated
- 19 Dec 2014
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 19837906Lorusso 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.
PubMed 23032618
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protocol EC-FV-01: A Phase 1 Study of EC145 Administered in Weeks 1 and 3 of a 4-Week Cycle
- ClinicalTrials.gov ID
- NCT00308269
- Acronym / sponsor ID
- 8109-006
- Conditions
- Cancer
- Keywords
- Cancer, Phase I, EC145, Recurrent, Refractory, Solid Tumors, Experimental
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- EndocyteIndustry (pharma, biotech, devices)
- Study start
- Mar 2006
- Primary completion
- Aug 2007 (actual)
- Study completion
- Jul 2008 (actual)
- First posted
- 29 Mar 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Vintafolide 1.2 mg IV Bolus | Experimental | Drug: Vintafolide IV BolusVintafolide 1.2 mg administered by IV bolus on Days 1, 3, 5, 15, 17, and 19 of 4-week treatment cycles |
| Vintafolide 2.5 mg IV Bolus | Experimental | Drug: Vintafolide IV BolusVintafolide 2.5 mg administered by IV bolus on Days 1, 3, 5, 15, 17, and 19 of 4-week treatment cycles |
| Vintafolide 4.0 mg IV Bolus | Experimental | Drug: Vintafolide IV BolusVintafolide 4.0 mg administered by IV bolus on Days 1, 3, 5, 15, 17, and 19 of 4-week treatment cycles |
| Vintafolide 2.5 mg IV Infusion | Experimental | Drug: Vintafolide IV InfusionVintafolide 2.5 mg administered by a 1-hour IV infusion on Days 1, 3, 5, 15, 17, and 19 of 4-week treatment cycles |
| Vintafolide 3.0 mg IV Infusion | Experimental | Drug: Vintafolide IV InfusionVintafolide 3.0 mg administered by a 1-hour IV infusion on Days 1, 3, 5, 15, 17, and 19 of 4-week treatment cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vintafolide IV BolusVintafolide is a folic acid desacetylvinblastine hydrazide conjugate | Drug | Vintafolide 1.2 mg IV Bolus, Vintafolide 2.5 mg IV Bolus, Vintafolide 4.0 mg IV Bolus |
| Vintafolide IV InfusionVintafolide is a folic acid desacetylvinblastine hydrazide conjugate | Drug | Vintafolide 2.5 mg IV Infusion, Vintafolide 3.0 mg IV Infusion |
Primary outcome
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.
8 secondary outcomes
Number of Participants with Best Overall Tumor Response: Participants with Folate Receptor Positive Tumors at Baseline
Time frame: Up to Week 24
Number of Participants with a Dose-Limiting Toxiciity During Cycle 1 Treatment
Time frame: Up to Day 26 in Treatment Cycle 1
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
Number of Participants with Best Overall Tumor Response: All Treated Participants
Time frame: Up to Week 24
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2014.
- Results publication: PubMed 19837906Li 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.
- Results publication: PubMed 23032618Lorusso 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vintafolide IV Bolus and Vintafolide IV Infusion in people with Cancer, run by Endocyte at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose During Cycle 1 Treatment (time frame: Up to Day 26 in Treatment Cycle 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00308269, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2014.