진행성 고형 종양이 있는 성인에게 단독 투여 시 IPN01194를 평가하기 위한 연구
진행성 고형 종양이 있는 성인 참가자를 대상으로 단일 제제로서 ERK1/2 억제제 IPN01194의 안전성, 내약성, 약동학, 약력학 및 항종양 활성을 평가하기 위한 공개 라벨 제I/IIa상 최초 인간 대상 용량 증량 및 코호트 확장 연구
The purpose of this study is to determine the appropriate dosage, safety and effectiveness of the study drug, IPN01194 in adults with advanced solid tumours.
The participants in this study will have advanced solid tumours. 'Advanced solid tumours' refers to cancers that can occur in several places, including cancers in organs or tissues that have spread from their original site to nearby tissues or other parts of the body.
In this study, all participants will receive the study drug, which will be taken by mouth (orally).
연구 개요
상세 설명
The study consists of two parts, called Phase I and Phase IIa.
Phase I is designed to assess the safety of increasing doses of IPN01194 in participants with specific types of advanced solid tumours.
The aim of this "dose escalation" phase is to find the dose range showing activity on the tumor that can be tolerated by the participants, and to determine the two doses for further testing in Phase IIa. Phase I will assess how the body processes and responds to the study drug when administered with and without food.
In Phase IIa, participants with selected single tumour type will be invited to take part. During this phase, the two dose levels of the study drug identified from Phase I will be tested. Participants will take the study drug one of the two dose levels. Each participant will be assigned to a dose level at random (by chance).
Each phase will consist of three periods:
- A period to assess eligibility (screening period) that will take up to 28 days.
- A treatment period of at least 28 days that will require at least two visits for the first month followed by one visit every month. There will be also one visit, at the end of treatment, at least 30 days after the last administration of study drug.
- A follow-up period (Phase IIa participants only), where every 3 months, participants will be contacted by phone, until death or the study cut-off date, whichever comes first.
Participants will undergo blood samplings, urine collections, physical examinations, and clinical evaluations. They may continue some other medications, but the details need to be recorded.
If in the opinion of the investigator a participant is continuing to experience clinical benefit after the cut-off date, the participant may remain in the study and continue to receive the study drug until either disease progression, unacceptable toxicity or other withdrawal criteria are met.
연구 유형
등록 (실제)
단계
- 2 단계
- 1단계
연락처 및 위치
연구 장소
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California
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Los Angeles, California, 미국, 90025
- The Angeles Clinic and Research Institute - California
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San Diego, California, 미국, 92037
- UC San Diego Health System - La Jolla
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Connecticut
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New Haven, Connecticut, 미국, 06510
- Yale Cancer Center - New Heaven
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Tennessee
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Nashville, Tennessee, 미국, 37203
- Sarah Cannon Research Institute (SCRI) - Nashville
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Virginia
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Fairfax, Virginia, 미국, 22031
- Virginia Cancer Specialist
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Barcelona, 스페인
- Barcelona - Val D'Hebron
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Madrid, 스페인
- Fundacion Jimenez Diaz - Madrid
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Madrid, 스페인
- M.D. Anderson Cancer Center Madrid
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Lyon, 프랑스
- Centre Léon Bérard - Lyon
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Paris, 프랑스
- Paris Saint-Louis
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Saint-Herblain, 프랑스
- Institut de Cancerologie de l'Ouest (St-Herblain)
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Villejuif, 프랑스
- IGR-Villejuif
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria :
- Participants must be ≥18 years of age
- Participants with histologically confirmed metastatic solid tumour (melanoma, metastatic colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC) or head and neck squamous cell carcinoma (HNSCC)) for whom no suitable alternative standard therapy exists.
- Participants must bear tumours harbouring selected classes of genetic mutations, (MAPKm).
- Participants must have measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1
- Eastern Cooperative Oncology Group (ECOG)/performance status (PS) of 0 or 1.
- Participants must consent to the use of archival tumour tissue or, if not available, collection of fresh tumour biopsy at screening
- Male and female participants Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical trials.
Exclusion Criteria
- Gastrointestinal conditions that could impair absorption of IPN01194 or inability to swallow oral medications.
- Any evidence of severe active infection or inflammatory condition.
- Non-adequate cardiac function
- Have one or more of study defined ophthalmological findings/conditions
- Known psychiatric or substance abuse disorder, or any other cognitive disorder per the opinion of the investigator that would interfere with the participant's ability to cooperate with the requirements of the study.
- Underlying medical conditions that, in the investigator's or sponsor's opinion, will obscure the interpretation of toxicity determination or AEs.
- Known second malignancy within the last 2 years prior to first dose of study intervention..
- Major surgery within 28 days prior to first dose of study intervention.
- Ongoing AEs caused by any prior anti-cancer therapy ≥Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0).
- Active brain metastases or leptomeningeal metastases
- Current enrolment or past participation in any other clinical trial involving an investigational study treatment within the last 28 days.
- Live vaccine(s) within 28 days prior to first dose of study intervention
- Concurrent treatment with any other anti-cancer therapy (including radiotherapy or investigational agents).
- Treatment with medications that prolong the QT/QTc interval.
- Treatment with strong and moderate CYP3A4 inducers
- Treatment with strong or moderate inhibitors of CYP3A4
- Only for Phase I participants assigned to dose escalation and low-dose backfill participants: treatment with proton pump inhibitors within 14 days prior to first dose of study intervention.
- Non-adequate bone marrow function
- Non-adequate renal function
- Non-adequate hepatic function
- Non adequate coagulation function.
- Known uncontrolled human immunodeficiency virus (HIV) infection or hepatitis B or C
- Sensitivity to IPN01194 or any of its components.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 순차적 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Phase I (Dose Escalation with Backfilling)
Nine dose levels are planned to be tested. |
IPN01194 will be taken orally over a period of 28 days (a "Cycle") at the assigned dose level. The dose limiting toxicity (DLT) observation period consists of the first 28 days of treatment with IPN01194 (Cycle 1). Participants will receive IPN01194 treatment beyond Cycle 1 until treatment is precluded by toxicity, disease progression, or upon participant's request or investigator decision. All participants will receive IPN01194 orally for 28-day cycles at one of the two dose levels determined at the end of Phase I. Participants will receive IPN01194 treatment until treatment is precluded by toxicity, disease progression, or upon participant's request or investigator decision |
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실험적: Phase IIa (Cohort Expansion)
Study intervention will be administered at one of two doses of interest determined at the end of Phase I. |
IPN01194 will be taken orally over a period of 28 days (a "Cycle") at the assigned dose level. The dose limiting toxicity (DLT) observation period consists of the first 28 days of treatment with IPN01194 (Cycle 1). Participants will receive IPN01194 treatment beyond Cycle 1 until treatment is precluded by toxicity, disease progression, or upon participant's request or investigator decision. All participants will receive IPN01194 orally for 28-day cycles at one of the two dose levels determined at the end of Phase I. Participants will receive IPN01194 treatment until treatment is precluded by toxicity, disease progression, or upon participant's request or investigator decision |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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1단계: 용량 제한 독성(DLT)이 있는 참가자의 비율
기간: 첫 접종 후 28일 이내
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첫 접종 후 28일 이내
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1단계: 투여를 중단하고 영구적으로 치료를 중단한 참가자의 비율
기간: 연구 개입의 마지막 투여 후 30일째
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연구 개입의 마지막 투여 후 30일째
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Phase 1: Percentage of participants experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TE SAEs)
기간: At 30 days following the last administration of study intervention
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An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
At 30 days following the last administration of study intervention
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Phase 2a: Objective response rate (ORR)
기간: At end of treatment (up to approximately 32 months)
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Defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator. |
At end of treatment (up to approximately 32 months)
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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1단계: IPN01194의 단일 및 다중 투여 후 관찰된 최대 약물 농도(Tmax)까지의 시간
기간: 1일차와 15일차.
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1일차와 15일차.
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1단계: IPN01194의 단일 및 다중 투여 후 관찰된 최대 약물 농도(Cmax)
기간: 1일차와 15일차.
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1일차와 15일차.
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1단계: 공복 상태 대비 급식 상태에서 투여된 IPN01194의 Cmax의 기하 평균 비율
기간: -8일과 -3일 사이(단식 기간) 및 -10일과 -7일 사이(급식 기간)
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-8일과 -3일 사이(단식 기간) 및 -10일과 -7일 사이(급식 기간)
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2a단계: 4개월 후 PFS 비율
기간: 무작위 배정부터 4개월까지
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무작위 배정부터 4개월까지
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2a단계: TEAE 및 TE SAE 참가자 비율
기간: 치료 종료 시(최대 약 32개월)
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치료 종료 시(최대 약 32개월)
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2a상: 투여를 중단하고 영구적으로 치료를 중단한 참가자의 비율
기간: 치료 종료 시(최대 약 32개월)
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치료 종료 시(최대 약 32개월)
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Phase 1: Area under the plasma concentration time curve (AUCtau) after single and multiple doses of IPN01194
기간: At Day 1 and Day 15.
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AUCtau is defined as the concentration of drug over one dosing interval. |
At Day 1 and Day 15.
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Phase 1: Geometric mean ratio of AUClast of IPN01194 administered in fed state relative to fasted state
기간: Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
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AUClast is defined as the concentration of drug from time zero to the last observable concentration. |
Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
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Phase 1: Geometric mean ratio of AUCinf administered in fed state relative to fasted state
기간: Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
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AUCinf is defined as the concentration of drug extrapolated to infinite time. |
Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
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Phase 1: Prolongation of corrected QT interval (QTc)
기간: Within 28 days of first dose
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Prolongation of QTc defined as the upper limit of 90% confidence interval for change from baseline QTc evaluated over Cycle 1 at the highest clinically relevant exposure. |
Within 28 days of first dose
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Phase 1: Objective response rate (ORR)
기간: At end of treatment (up to approximately 32 months)
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The ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR). |
At end of treatment (up to approximately 32 months)
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Phase 2a: Duration of response (DoR)
기간: From randomisation to end of treatment (up to approximately 32 months)
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Defined as the percentage of participants with BOR of CR or PR, as determined by investigator per RECIST version 1.1 |
From randomisation to end of treatment (up to approximately 32 months)
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Phase 2a: Progression-free survival (PFS)
기간: From randomisation to end of treatment (up to approximately 32 months)
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PFS is defined as the time from the date of randomisation to the date of the first documented disease progression, as determined by investigator per RECIST version 1.1. |
From randomisation to end of treatment (up to approximately 32 months)
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Phase 2a: Disease control rate (DCR)
기간: At end of treatment (up to approximately 32 months)
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DCR is defined as the percentage of participants with BOR of CR, PR or stable disease (SD), as determined by investigator per RECIST version 1.1. |
At end of treatment (up to approximately 32 months)
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공동 작업자 및 조사자
스폰서
수사관
- 연구 책임자: Ipsen Medical Director, Ipsen
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- CLIN-01194-450
- 2023-506228-10-00 (기타 식별자: Ipsen)
- 2023 (미국 NIH 보조금/계약)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications.
Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.
IPD 공유 기간
Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and/or EU.
IPD 공유 액세스 기준
Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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