Phase I Safety Study of the Drug MM-121 in Patients With Advanced Solid Tumors Resisting Ordinary Treatment
2016년 8월 30일 업데이트: Merrimack Pharmaceuticals
A Phase I and Pharmocologic Study of MM-121 in Patients With Refractory Advanced Solid Tumors
This study was a Phase 1 and pharmacologic open-labeled dose-escalation trial using a "3+3" design to determine maximum tolerated dose/recommended Phase 2 dose.
연구 개요
상세 설명
Successive cohorts of three or more patients were treated at escalating doses until a maximum tolerated dose/recommended phase 2 dose was identified.
The study initially explored a dosing schedule every 7-days, which may have been modified to longer intervals under certain circumstances but did not expand to more than weekly.
When the maximum tolerated dose/recommended Phase 2 dose was identified, an Expansion Cohort was enrolled at that dose to further characterize safety and to explore pharmacodynamic endpoints.
There were 3 sites that participated.
연구 유형
중재적
등록 (실제)
44
단계
- 1단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Massachusetts
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Boston, Massachusetts, 미국, 02115-6084
- Dana-Farber Cancer Institute
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Pennsylvania
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Philadelphia, Pennsylvania, 미국, 19111
- Fox Chase Cancer Center
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Tennessee
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Nashville,, Tennessee, 미국, 37232
- The Vanderbilt-Ingram Cancer Center
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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:
- Patients must have histologically or cytologically confirmed advanced solid tumors that have recurred or progressed following standard therapy, or that have not responded to standard therapy, or for which there is no standard therapy, or who are not candidates for standard therapy
- Patients must be > 18 years of age
- Patients or their legal representatives must be able to understand and sign an informed consent form
Patients must have evaluable or measurable tumor(s)
- Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy. Up to CTCAE Grade 1 is acceptable for patients with known peripheral neuropathy.
- Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-121 (an effective form of contraception is an oral contraceptive or a double barrier method)
In addition, patients to be enrolled the Expansion Cohort must have/be:
- Advanced/metastatic breast cancer with histological/cytological documentation of ER-, PR-, Her2/neu non-over-expressing breast cancer (triple negative breast cancer); OR,
- Patients must have advanced/metastatic breast cancer with histologically or cytologically confirmed ER+ and/or PR+, Her2/neu non-over-expxressing OR,
- Patients must have advanced/metastatic histological confirmation of epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer; OR,
- Additional tumor types such as metastatic colorectal, advanced non small cell lung cancer, and others may be considered on a per-patient basis
- Tumor tissue amenable to biopsy
- Platelet counts, partial thromboplastin time (PTT) and international normalized ratio (INR) within normal limits.
- Willing to undergo tumor biopsy twice (once before and once after treatment with MM-121)
- Blocks of archived formalin-fixed, paraffin-embedded, unstained tumor tissue available for submission. Patients with no available archived tumor tissue available must receive Sponsor approval prior to enrollment.
Exclusion Criteria:
- Patients for whom potentially curative antineoplastic therapy is available
- Patients who are pregnant or lactating
- Patients with an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing. (At the discretion of the investigator, patients with tumor fever may be enrolled.)
- Patients with untreated and/or symptomatic CNS malignancies (primary or metastatic); patients with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trial
- NYHA Class III or IV congestive heart failure or LVEF < 55%
- Known HIV, hepatitis B or C (active, previously treated or both)
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: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Dose Escalation
Cohorts of escalating doses of MM-121 administered IV QW to determine MTD or RP2D + expansion cohort at MTD/RP2D
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Dose escalation Frequency - once weekly
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Objective Response Rate and Duration
기간: Time from first dose to date of progression, with a median of 7.1 weeks
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To determine the number of patients reporting an objective response using RECIST v 1.1 where a Partial Response is defined as a >20% decrease in tumor burden from baseline and a Complete Response is defined as complete disappearance of tumor burden from baseline. Duration of response is defined as the length of time in weeks from observation of response until progression. NOTE: because no patients experienced an objective response as shown below, duration of response is not presented. No duration of response could be measured. |
Time from first dose to date of progression, with a median of 7.1 weeks
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Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities
기간: From date of first dose to 30 days after termination, the longest 47 weeks
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Using a 3+3 dose escalation model, the maximum tolerated dose was determined by assessing dose-limiting toxicities in each cohort from cohort 1-6.
Cohort 1 began at 3.2 mg/kg IV QW and the dose escalated in separate cohorts from 6 mg/kg IV QW, 10 mg/kg IV QW, 15 mg/kg IV QW, 20 mg/kg IV QW, to the highest scheduled testing dose at 40 mg/kg one-time loading dose on cycle 1, week 1 followed by 20 mg/kg IV QW maintenance doses.
If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated.
If a DLT was reported, 3-4 additional patients were enrolled and observed.
If a DLT was observed in the expanded cohort, this dose was considered to be the maximum tolerated dose.
The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs.
The determined MTD was considered the Recommended Phase 2 Dose and was used to open the expansion cohort.
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From date of first dose to 30 days after termination, the longest 47 weeks
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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To Describe the Dose-limiting Toxicity of MM-121 as a Monotherapy
기간: From date of first dose to 30 days after termination, the longest 47 weeks
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To establish the safety of escalating doses of MM-121 administered as a monotherapy in order to determine the recommended phase 2 dose.
Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose.
Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD to be used for the expansion cohort.
DLTs were not measured in the Expansion Cohort.
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From date of first dose to 30 days after termination, the longest 47 weeks
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To Determine the Pharmacokinetic and Immunogenicity Parameters of MM-121
기간: At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients
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Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. The maximum observed concentration (Cmax) is presented and was calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (3.2 mg/kg, 6 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 40/20 mg/kg). Immunogenicity data is not available. |
At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients
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To Determine the Pharmacokinetic Parameters of MM-121
기간: At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients
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Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121.
The AUC is presented and was calculated usig Non-compartmental analysis (NCA).
Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA).
Data is presented per dose level of MM-121 (3.2 mg/kg, 6 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 40/20 mg/kg).
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At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
협력자
수사관
- 수석 연구원: Kwok Kin Wong, MD, Dana-Farber Cancer Institute
- 수석 연구원: Keedy L Vicki, MD, Vanderbilt University Medical Center
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
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
2008년 7월 1일
기본 완료 (실제)
2010년 5월 1일
연구 완료 (실제)
2013년 9월 1일
연구 등록 날짜
최초 제출
2008년 8월 12일
QC 기준을 충족하는 최초 제출
2008년 8월 12일
처음 게시됨 (추정)
2008년 8월 14일
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
2016년 9월 1일
QC 기준을 충족하는 마지막 업데이트 제출
2016년 8월 30일
마지막으로 확인됨
2016년 8월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- MM-121-01-100
- MM-121
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
아니
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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