- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01688791
A Study of MK-8109 (Vintafolide) Given Alone or With Chemotherapy in Participants With Advanced Cancers (MK-8109-001)
February 9, 2015 updated by: Endocyte
A Phase I Dose Escalation Study Evaluating Vintafolide (MK-8109) Chemotherapy Alone or in Combination in Adult Subjects With Advanced Cancers
This trial will be conducted in three parts.
Part A is a dose escalation trial followed by a dose confirmation trial in folate receptor (FR) 100% endometrial cancer participants.
The primary hypothesis of this trial is that administration of vintafolide in combination with carboplatin and paclitaxel is safe and tolerable.
Part B is a single dose, dose escalation, pharmacokinetic (PK), and QTc interval trial.
The primary objectives include determination of the maximum single tolerated dose of vintafolide and to evaluate the effect of this single maximum dose on the QTc interval.
Part C is a weekly dose escalation trial of vintafolide followed by a dose confirmation.
The primary hypothesis of this part is that weekly vintafolide has acceptable safety and tolerability in participants with advanced cancers.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
37
Phase
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion criteria for all participants:
- Histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist or is unacceptable to the participant
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- At least one measurable metastatic or recurrent lesion
- No history of a previous malignancy with the exception of cervical intraepithelial neoplasia, basal cell carcinoma of the skin, or adequately treated localized prostate carcinoma; or has undergone potentially curative therapy with no evidence of disease for five years
- Adequate organ function
- Female participants of childbearing potential must be willing to use acceptable methods of birth control or abstain from heterosexual activity for the course of the study through 90 days after the last dose of study therapy
- Male participants must agree to use an adequate method of contraception for heterosexual activity starting with the first dose of study therapy through 90 days after the last dose of study therapy
Inclusion criteria for Part A:
- Tumor lesions characterized as folate receptor (FR) 100% as determined by an etarfolide Sequential Single Photon Emission Computed Tomography (SPECT) and CT scan
- Histologically-confirmed diagnosis of locally advanced or metastatic or recurrent endometrial cancer
Inclusion criteria for Parts B & C:
- Must have an etarfolatide SPECT/CT scan to determine FR status
Exclusion criteria for all participants:
- Part A & Part C if enrolled after completion of Part B: Chemotherapy, radiotherapy, or biological therapy (including monoclonal antibodies) within 4 weeks prior to drug administration, or not recovered from adverse events due to agents administered more than 4 weeks earlier
- Part B: Chemotherapy, radiotherapy, or biological therapy (including monoclonal antibodies) within 3 weeks prior to drug administration, or not recovered from adverse events due to agents administered more than 4 weeks earlier
- Currently participating or has participated in a study with an investigational compound or device within 28 days of initial dosing on this study
- Part A, dose escalation, Parts B and C: More than 3 prior cytotoxic regimens for metastatic disease.
- Part A, dose confirmation: Has received more than 2 prior cytotoxic regimens for metastatic disease.
- Primary central nervous system (CNS) tumor
- Active CNS metastases and/or carcinomatous meningitis.
- Known hypersensitivity to the components of the study therapy or its analogs
- Recent (i.e., ≤ 6 weeks) history of abdominal surgery or peritonitis
- Bowel occlusion or sub-occlusion
- Prior whole abdominal or whole pelvis radiation therapy or radiation therapy to >10% of the bone marrow at any time in the past or prior radiation therapy within the last 3 years to the breast / sternum, head, or neck
- Requires anti-folate therapy for the management of co-morbid conditions
- Known regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse
- Pregnant or breastfeeding or expecting to conceive, or donate sperm within the span of the study
- Human Immunodeficiency Virus (HIV)-positive
- Active Hepatitis B or C
- Symptomatic ascites or pleural effusion.
- History of stem cell or bone marrow transplant
Exclusion Criteria for Part B:
- Permanent pacemaker
- Unable to refrain from use of all concomitant medications on Day 1
- Structural heart disease, history of myocardial infarction (MI), or unstable angina
- History of cardiac arrhythmia, congestive heart failure (CHF), sick sinus syndrome, second or third degree atrioventricular (AV) block
- History of risk factors for Torsades de Pointes such as CHF, uncorrected hypokalemia, family history of long QT syndrome
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part A: Vintafolide BIW
Vintafolide, intravenously (IV), on Days 1, 4, 8, and 11 of each 21-day cycle.
Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle.
Paclitaxel, IV, at a dose of 175 mg/m^2, administered on Day 1 of each 21-day cycle
|
Other Names:
|
Experimental: Part A: Vintafolide TIW
Vintafolide, intravenously (IV) on Days 1, 3, 5, 8, 10, and 12 of each 21-day cycle.
Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle.
Paclitaxel, IV, at a dose of 175 mg/m^2, administered on Day 1 of each 21-day cycle
|
Other Names:
|
Experimental: Parts B & C: Vintafolide Single Dose & Weekly (QW)
Single dose, dose escalation, vintafolide (Part B) followed by 2 week observation.
Those completing Part B will have the option to continue on to Part C (weekly dosing, dose finding, on Days 1, 8, and 15 in a 21-day cycle until disease progression or toxicity) unless they experience severe and/or persistent drug related toxicity.
|
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Parts A and C: Number of participants with dose-limiting toxicities (DLTs)
Time Frame: Cycle 1 (21 days)
|
Cycle 1 (21 days)
|
Part B: Change from Baseline in QTc interval
Time Frame: 30 minutes pre-dose and up to 2 hours post-dose
|
30 minutes pre-dose and up to 2 hours post-dose
|
Part C: Number of Participants Experiencing an Adverse Event (AE)
Time Frame: Up to 18 weeks (six 3-week cycles)
|
Up to 18 weeks (six 3-week cycles)
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of participants whose best response is partial response (PR) or complete response (CR)
Time Frame: Week 6
|
Week 6
|
Progression free survival
Time Frame: Week 6
|
Week 6
|
Disease control rate
Time Frame: Week 6
|
Week 6
|
Part B: Pharmacokinetics (PK) of vintafolide, including Area Under the Curve (AUC) and Maximum Concentration (Cmax)
Time Frame: Day 1
|
Day 1
|
Part B: PK of Vintafolide Metabolites, including AUC and Cmax
Time Frame: Day 1
|
Day 1
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2012
Primary Completion (Actual)
September 1, 2014
Study Completion (Actual)
September 1, 2014
Study Registration Dates
First Submitted
September 17, 2012
First Submitted That Met QC Criteria
September 17, 2012
First Posted (Estimate)
September 20, 2012
Study Record Updates
Last Update Posted (Estimate)
February 10, 2015
Last Update Submitted That Met QC Criteria
February 9, 2015
Last Verified
February 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 8109-001
- 2012-002799-14 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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