A Study of Hedgehog Pathway Inhibitor GDC-0449 in Patients With Locally Advanced or Metastatic Solid Tumors That Are Refractory to Standard Therapy or for Whom No Standard Therapy Exists
2017年6月8日 更新者：Genentech, Inc.
A Phase Ib, Open-Label, Dose-Scheduling Study of Hedgehog Pathway Inhibitor GDC-0449 in Patients With Locally Advanced or Metastatic Solid Tumors That Are Refractory to Standard Therapy or for Whom No Standard Therapy Exists
This is a two stage, Phase Ib study designed to describe the pharmacokinetics of GDC-0449 in patients with advanced solid tumors that are refractory to treatment or for whom no standard therapy exists.
調査の概要
研究の種類
介入
入学 (実際)
67
段階
- フェーズ 1
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria
- Histologically documented, incurable, locally advanced or metastatic solid malignancy that has progressed after first-line and second-line therapy (if there is a second-line therapy that has been shown to provide clinical benefit); patients with basal cell carcinoma will be excluded from this study unless they do not qualify for another open GDC-0449 clinical trial
- For patients with disease that is evaluable by physical examination only, diagnosis must also include biomarker confirmation
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Documented negative pregnancy test for women of childbearing potential and agreement to use an effective form of contraception for the duration of the study
- Adequate hematopoietic capacity
- Adequate hepatic function
- Adequate renal function
- At least 3 weeks since last chemotherapy, investigational agent, radiation therapy, or major surgical procedure and recovery to pre-treatment baseline or stabilization of all treatment-related toxicities
Exclusion Criteria
- Known, untreated central nervous system (CNS) malignancies or treated brain metastases that are not radiographically stable for ≥ 3 months
- Active infection requiring intravenous (IV) antibiotics
- Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with hepatitis
- Any medical condition or diagnosis that would likely impair absorption of an orally administered drug (e.g., gastrectomy, ileal bypass, chronic diarrhea, gastroparesis)
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications
- Pregnant or lactating
- Treatment with excluded medications, including strong CYP450 inhibitors and inducers
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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：並列代入
- 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：あ
|
Daily oral repeating dose
Three times weekly oral repeating dose
Once weekly oral repeating dose
|
|
実験的：B
|
Daily oral repeating dose
Three times weekly oral repeating dose
Once weekly oral repeating dose
|
|
実験的：ハ
|
Daily oral repeating dose
Three times weekly oral repeating dose
Once weekly oral repeating dose
|
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 |
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady-State for Both Total and Unbound GDC-0449
時間枠：Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
|
Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
|
|
|
Number of Participants With Greater Than (>) 50 Percent (%) Decrease in Trough Concentration at Steady State (Css, Trough)
時間枠：Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
|
Percent change = ([trough concentration on Day 15 minus trough concentration on Day 57] divided by trough concentration on Day 15) multiplied by 100.
|
Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
|
|
Ratio of Total and Unbound Trough GDC-0449 Concentration Between Day 57 to Day 15
時間枠：Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
|
Ratio = trough concentration on Day 57 divided by trough concentration on Day 15.
If the ratio of total and unbound trough GDC-0449 concentration between Day 57 to Day 15 is less than 1, then it indicates reduction in total and unbound trough GDC-0449 concentration between Day 15 to Day 57.
|
Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
|
|
Plasma Concentration at Steady State (Css) for Total and Unbound GDC-0449
時間枠：Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
|
Plasma GDC-0449 concentrations were reported in nanogram per milliliter (ng/mL) units and converted to micromolar (mcM) units using the molecular weight (421.30
grams per mole [g/mol]) prior to PK analysis.
Css was calculated for Days 28 to 56.
|
Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
|
|
Maximum Plasma Concentration (Cmax) of Total and Unbound GDC-0449
時間枠：0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1, 15 and 57 post-dose
|
Plasma GDC-0449 concentrations were reported in ng/mL units and converted to mcM units using the molecular weight (421.30
g/mol) prior to PK analysis.
|
0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1, 15 and 57 post-dose
|
|
Area Under the Curve From Time Zero to 24 Hour (AUC0-24) for Total and Unbound GDC-0449
時間枠：Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
|
AUC is a measure of the serum concentration of the drug over time.
It is used to characterize drug absorption.
AUC values were calculated using the linear trapezoidal method when the concentrations were rising and using the logarithmic trapezoidal method when the concentrations were declining (linear up/log down rule in WinNonlin).
Below the limit of quantitation (BLQ) values at pre-dose were considered as zero for PK analysis.
|
Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
|
|
Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) for Total and Unbound GDC-0449
時間枠：Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
|
AUC values were calculated using the linear trapezoidal method when the concentrations were rising and using the logarithmic trapezoidal method when the concentrations were declining (linear up/log down rule in WinNonlin).
BLQ values at pre-dose were considered as zero for PK analysis.
|
Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
|
|
Time to Achieve Maximum Observed Plasma Concentration (Tmax) After a Single Dose of GDC-0449
時間枠：0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1
|
0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Percentage of Participants With Disease Progression or Death
時間枠：Screening, Day 57, and every 8 weeks thereafter up to 52 weeks
|
Disease progression (assessed by Response Evaluation Criteria in Solid Tumors [RECIST]) was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions or the appearance of one or more new lesions and/or unequivocal progression of existing non target lesions.
|
Screening, Day 57, and every 8 weeks thereafter up to 52 weeks
|
|
Percentage of Participants With a Response by Best Overall Response (BOR)
時間枠：Screening Day 57, and every 8 weeks thereafter up to 52 weeks
|
BOR was defined as the best overall response observed during the treatment period according to RECIST.
CR: disappearance of all TLs, with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 mm.
PR: at least a 30% decrease in the sum of diameters of TLs, taking as reference the BL sum diameters.
Progressive disease (PD): at least a 20% increase in the sum of diameters of TLs, taking as a reference the smallest sum on study (this included the baseline sum if that is the smallest on study).
In addition to the relative increase in 20%, the sum must also have demonstrated an absolute increase of at least 5 mm.
Stable disease (SD) was defined as neither sufficient shrinkages to qualify for PR, nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
|
Screening Day 57, and every 8 weeks thereafter up to 52 weeks
|
|
Progression-Free Survival (PFS) Time
時間枠：Screening Day 57, and every 8 weeks thereafter up to 52 weeks
|
PFS defined as the time from study treatment initiation to the first occurrence of disease progression, as determined by the investigator review of tumor assessments using RECIST, or death from any cause during the study (i.e., within 30 days after the last dose of study treatment).
|
Screening Day 57, and every 8 weeks thereafter up to 52 weeks
|
|
Duration of Response (DR)
時間枠：Screening Day 57, and every 8 weeks thereafter up to 52 weeks
|
DR during first line therapy is defined as the time from when response (complete response [CR] or partial response [PR]) was first documented to first documented disease progression or death (whichever occurs first) during first line therapy.
This was only be calculated for participants who achieved a best overall response of CR or PR.
Participants who did not progress or die after they had a confirmed response were censored at the date of their last tumor measurement or last follow up for progression of disease during first line therapy.
CR: disappearance of all target lesions (TLs) with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 millimeters.
PR: at least a 30% decrease in the sum of diameters of TLs, with reference to baseline sum diameters.
DR was not calculated as only 1 responding participant reached their response at the last scheduled response assessment, hence follow-up data are not available.
|
Screening Day 57, and every 8 weeks thereafter up to 52 weeks
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- スタディディレクター：Jennifer Low, M.D.、Genentech, Inc.
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2009年9月1日
一次修了 (実際)
2010年10月1日
研究の完了 (実際)
2010年10月1日
試験登録日
最初に提出
2009年8月28日
QC基準を満たした最初の提出物
2009年8月28日
最初の投稿 (見積もり)
2009年8月31日
学習記録の更新
投稿された最後の更新 (実際)
2017年7月11日
QC基準を満たした最後の更新が送信されました
2017年6月8日
最終確認日
2017年6月1日
詳しくは
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。