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

2015년 2월 9일 업데이트: 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.

연구 개요

연구 유형

중재적

등록 (실제)

37

단계

  • 1단계

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위화되지 않음
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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
다른 이름들:
  • MK-8109
  • EC-145
실험적: 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
다른 이름들:
  • MK-8109
  • EC-145
실험적: 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.
다른 이름들:
  • MK-8109
  • EC-145

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
기간
Parts A and C: Number of participants with dose-limiting toxicities (DLTs)
기간: Cycle 1 (21 days)
Cycle 1 (21 days)
Part B: Change from Baseline in QTc interval
기간: 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)
기간: Up to 18 weeks (six 3-week cycles)
Up to 18 weeks (six 3-week cycles)

2차 결과 측정

결과 측정
기간
Number of participants whose best response is partial response (PR) or complete response (CR)
기간: Week 6
Week 6
Progression free survival
기간: Week 6
Week 6
Disease control rate
기간: Week 6
Week 6
Part B: Pharmacokinetics (PK) of vintafolide, including Area Under the Curve (AUC) and Maximum Concentration (Cmax)
기간: Day 1
Day 1
Part B: PK of Vintafolide Metabolites, including AUC and Cmax
기간: Day 1
Day 1

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작

2012년 12월 1일

기본 완료 (실제)

2014년 9월 1일

연구 완료 (실제)

2014년 9월 1일

연구 등록 날짜

최초 제출

2012년 9월 17일

QC 기준을 충족하는 최초 제출

2012년 9월 17일

처음 게시됨 (추정)

2012년 9월 20일

연구 기록 업데이트

마지막 업데이트 게시됨 (추정)

2015년 2월 10일

QC 기준을 충족하는 마지막 업데이트 제출

2015년 2월 9일

마지막으로 확인됨

2015년 2월 1일

추가 정보

이 연구와 관련된 용어

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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