進行性固形腫瘍を有する成人にIPN01194を単独投与した場合の評価に関する研究
進行性固形腫瘍を有する成人参加者における単剤としてのERK1/2阻害剤IPN01194の安全性、忍容性、薬物動態学的、薬力学および抗腫瘍活性を評価するための非盲検第I/IIa相ファーストインヒト、用量漸増およびコホート拡大研究
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).
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
-
-
California
-
Los Angeles、California、アメリカ、90025
- The Angeles Clinic and Research Institute - California
-
San Diego、California、アメリカ、92037
- UC San Diego Health System - La Jolla
-
-
Connecticut
-
New Haven、Connecticut、アメリカ、06510
- Yale Cancer Center - New Heaven
-
-
Tennessee
-
Nashville、Tennessee、アメリカ、37203
- Sarah Cannon Research Institute (SCRI) - Nashville
-
-
Virginia
-
Fairfax、Virginia、アメリカ、22031
- Virginia Cancer Specialist
-
-
-
-
-
Barcelona、スペイン
- Barcelona - Val D'Hebron
-
Madrid、スペイン
- Fundacion Jimenez Diaz - Madrid
-
Madrid、スペイン
- M.D. Anderson Cancer Center Madrid
-
-
-
-
-
Lyon、フランス
- Centre Léon Bérard - Lyon
-
Paris、フランス
- Paris Saint-Louis
-
Saint-Herblain、フランス
- Institut de Cancerologie de l'Ouest (St-Herblain)
-
Villejuif、フランス
- IGR-Villejuif
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：順次割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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 |
|
実験的：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 |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
フェーズ 1: 用量制限毒性 (DLT) のある参加者の割合
時間枠：初回投与から28日以内
|
初回投与から28日以内
|
|
|
フェーズ 1: 投与中断および治療の永久中止を行った参加者の割合
時間枠：研究介入の最後の投与から30日後
|
研究介入の最後の投与から30日後
|
|
|
Phase 1: Percentage of participants experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TE SAEs)
時間枠：At 30 days following the last administration of study intervention
|
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
|
|
Phase 2a: Objective response rate (ORR)
時間枠：At end of treatment (up to approximately 32 months)
|
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)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
フェーズ 1: IPN01194 の単回および複数回投与後の観察される最大薬物濃度 (Tmax) までの時間
時間枠：1日目と15日目。
|
1日目と15日目。
|
|
|
フェーズ 1: IPN01194 の単回および複数回投与後の最大観察薬物濃度 (Cmax)
時間枠：1日目と15日目。
|
1日目と15日目。
|
|
|
フェーズ 1: 絶食状態に対する摂食状態で投与された IPN01194 の Cmax の幾何平均比
時間枠：-8 日目と -3 日目の間 (絶食期間)、および -10 日目と -7 日目の間 (摂食期間)
|
-8 日目と -3 日目の間 (絶食期間)、および -10 日目と -7 日目の間 (摂食期間)
|
|
|
フェーズ 2a: 4 か月時点の PFS 率
時間枠：ランダム化から 4 か月まで
|
ランダム化から 4 か月まで
|
|
|
フェーズ 2a: TEAE および TE SAE を有する参加者の割合
時間枠：治療終了時（最長約32ヶ月）
|
治療終了時（最長約32ヶ月）
|
|
|
フェーズ 2a: 投与中断および治療の永久中止を行った参加者の割合
時間枠：治療終了時（最長約32ヶ月）
|
治療終了時（最長約32ヶ月）
|
|
|
Phase 1: Area under the plasma concentration time curve (AUCtau) after single and multiple doses of IPN01194
時間枠：At Day 1 and Day 15.
|
AUCtau is defined as the concentration of drug over one dosing interval. |
At Day 1 and Day 15.
|
|
Phase 1: Geometric mean ratio of AUClast of IPN01194 administered in fed state relative to fasted state
時間枠：Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
|
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)
|
|
Phase 1: Geometric mean ratio of AUCinf administered in fed state relative to fasted state
時間枠：Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
|
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)
|
|
Phase 1: Prolongation of corrected QT interval (QTc)
時間枠：Within 28 days of first dose
|
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
|
|
Phase 1: Objective response rate (ORR)
時間枠：At end of treatment (up to approximately 32 months)
|
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)
|
|
Phase 2a: Duration of response (DoR)
時間枠：From randomisation to end of treatment (up to approximately 32 months)
|
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)
|
|
Phase 2a: Progression-free survival (PFS)
時間枠：From randomisation to end of treatment (up to approximately 32 months)
|
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)
|
|
Phase 2a: Disease control rate (DCR)
時間枠：At end of treatment (up to approximately 32 months)
|
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)
|
協力者と研究者
スポンサー
捜査官
- スタディディレクター：Ipsen Medical Director、Ipsen
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- CLIN-01194-450
- 2023-506228-10-00 (その他の識別子：Ipsen)
- 2023 (米国 NIH グラント/契約)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
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 共有時間枠
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 共有アクセス基準
Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。