Trial record 5 of 10 for:    EC-145

A Study of MK-8109 (Vintafolide) Given Alone or With Chemotherapy in Participants With Advanced Cancers (MK-8109-001)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Endocyte
ClinicalTrials.gov Identifier:
NCT01688791
First received: September 17, 2012
Last updated: February 9, 2015
Last verified: February 2015
  Purpose

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.


Condition Intervention Phase
Advanced Cancer
Drug: Vintafolide
Drug: Carboplatin
Drug: Paclitaxel
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Study Evaluating Vintafolide (MK-8109) Chemotherapy Alone or in Combination in Adult Subjects With Advanced Cancers

Resource links provided by NLM:


Further study details as provided by Endocyte:

Primary Outcome Measures:
  • Parts A and C: Number of participants with dose-limiting toxicities (DLTs) [ Time Frame: Cycle 1 (21 days) ] [ Designated as safety issue: Yes ]
  • Part B: Change from Baseline in QTc interval [ Time Frame: 30 minutes pre-dose and up to 2 hours post-dose ] [ Designated as safety issue: Yes ]
  • Part C: Number of Participants Experiencing an Adverse Event (AE) [ Time Frame: Up to 18 weeks (six 3-week cycles) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of participants whose best response is partial response (PR) or complete response (CR) [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Progression free survival [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Disease control rate [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Part B: Pharmacokinetics (PK) of vintafolide, including Area Under the Curve (AUC) and Maximum Concentration (Cmax) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Part B: PK of Vintafolide Metabolites, including AUC and Cmax [ Time Frame: Day 1 ] [ Designated as safety issue: No ]

Enrollment: 37
Study Start Date: December 2012
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Vintafolide
Other Names:
  • MK-8109
  • EC-145
Drug: Carboplatin Drug: Paclitaxel
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
Drug: Vintafolide
Other Names:
  • MK-8109
  • EC-145
Drug: Carboplatin Drug: Paclitaxel
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.
Drug: Vintafolide
Other Names:
  • MK-8109
  • EC-145

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Endocyte
ClinicalTrials.gov Identifier: NCT01688791     History of Changes
Other Study ID Numbers: 8109-001, 2012-002799-14
Study First Received: September 17, 2012
Last Updated: February 9, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Carboplatin
Folic Acid
Paclitaxel
Vinca Alkaloids
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Growth Substances
Hematinics
Hematologic Agents
Micronutrients
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Tubulin Modulators
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on August 02, 2015