Study of XL147 (SAR245408) in Combination With Trastuzumab or Paclitaxel and Trastuzumab in Subjects With Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-based Regimen
A Phase 1/2 Study of XL147 (SAR245408) Administered in Combination With Trastuzumab or Paclitaxel and Trastuzumab in Subjects With Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-Based Regimen
Phase 1 of this study will evaluate the maximum tolerated dose (MTD) of XL147 when given in combination with trastuzumab (Herceptin) and in combination with trastuzumab and paclitaxel. After the MTD is established for each combination (Phase 2), subjects will be enrolled to evaluate the preliminary efficacy and safety of these combinations in metastatic HER2 positive breast cancer. Both trastuzumab and paclitaxel are used in the treatment of metastatic breast cancer (MBC), but patients can develop resistance.
The link between PI3K mutations and trastuzumab resistance has been seen in breast cancer patients. This suggests that inhibitors of the PI3K/PTEN pathway may have the potential to restore sensitivity to trastuzumab. Similarly, introduction of activated mutant forms of PI3K has been shown to transform and confer paclitaxel resistance to immortalized breast epithelial cells. XL147 is a potent and selective inhibitor of PI3K and inhibits phosphorylation of multiple downstream components of PI3K/PTEN signaling. Therefore, XL147 may have utility in the treatment of trastuzumab resistant/refractory and HER2-positive MBC when administered in combination with trastuzumab alone or with trastuzumab and paclitaxel.
調査の概要
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、90033
- Investigational Site Number 1537
-
-
Florida
-
Fort Meyers、Florida、アメリカ、33901
- Investigational Site Number 1238
-
-
Massachusetts
-
Boston、Massachusetts、アメリカ、02115
- Investigational Site Number 1138
-
-
Michigan
-
Detroit、Michigan、アメリカ、48201
- Investigational Site Number 1330
-
-
New York
-
Bronx、New York、アメリカ、10467
- Investigational Site Number 1151
-
New York、New York、アメリカ、10032
- Investigational Site Number 1150
-
-
Tennessee
-
Nashville、Tennessee、アメリカ、37203
- Investigational Site Number 1214
-
Nashville、Tennessee、アメリカ、37232
- Investigational Site Number 1246
-
-
-
-
-
Madrid、スペイン、28041
- Investigational Site Number 3413
-
-
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:
- The subject has pathologically and radiologically confirmed metastatic HER2 positive breast cancer (Stage IV disease). Subjects must have received and progressed on at least one prior trastuzumab-containing regimen for metastatic disease. For subjects in Arm 2, they must also have received at least one prior taxane-containing regimen.
- The subject has at least one lesion that is not within a previously radiated field and measurable on computerized tomography (CT) or magnetic resonance imaging scan (MRI)
- The subjects enrolled in Phase 2 must be willing to undergo a biopsy of the primary tumor or a tumor metastasis at baseline, if tumor tissue is amenable to biopsy
- The subject's primary tumor and/or metastatic lesion must overexpress HER2
- For subjects enrolled in Phase 2: samples from archival or fresh tissue, or a tissue block of the subject's tumor.
- The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- The subject has adequate organ and marrow function
- The subject is capable of understanding the informed consent and complying with the protocol and has signed the informed consent document prior to any study-specific screening procedures or evaluations being performed.
- Sexually active subjects must agree to use a medically-accepted barrier method of contraception during the course of the study and for 3 months following discontinuation of study treatments. For subjects using oral contraceptives, a barrier method must be used in addition to the oral contraceptive
- Subjects of childbearing potential must have a negative pregnancy test at screening and enrollment
Exclusion Criteria:
- The subject has previously been treated with a selective inhibitor of PI3K and / or AKT
- Certain restrictions on prior therapies apply
- The subject has not recovered from toxicity due to prior therapy to Grade ≤ 1 or to pre-therapy baseline
- The subject has untreated, symptomatic, or progressive brain metastases. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥4 weeks prior to first study treatment
- The subject has prothrombin time/International Normalized Ratio (PT/INR) or partial thromboplastin time (PTT) test results at screening that are ≥ 1.3 times above the laboratory upper limit of normal
- The subject has a diagnosis of uncontrolled diabetes mellitus
- The subject has uncontrolled significant intercurrent illness
- The subject has uncontrolled hypertension or other clinically significant cardiovascular disease
- The subject has left ventricular ejection fraction (LVEF) ≤ 50%
- The subject has a baseline corrected QT interval ≥ 460 ms
- The subject is currently receiving anticoagulation with therapeutic doses of warfarin (low-dose warfarin ≤ 1mg/day is permitted)
- The subject is pregnant or breastfeeding
- The subject is known to be positive for the human immunodeficiency virus (HIV) (a test for HIV at screening is not required)
- The subject has any other diagnosis of malignancy or evidence of malignancy (except non-melanoma skin cancer, in situ carcinoma of the cervix) within 2 years prior to screening for this study
- The subject has a previously identified allergy or hypersensitivity or is intolerant to components of any of the study treatment formulations
- The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
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:非ランダム化
- 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:Arm 1
XL147 in combination with trastuzumab
|
administered orally once daily as tablet(s)
administered by IV once every 3 weeks
他の名前:
|
実験的:Arm 2
XL147 in combination with trastuzumab and paclitaxel
|
administered orally once daily as tablet(s)
administered by IV once every 3 weeks
他の名前:
administered by IV once every week
|
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 |
時間枠 |
---|---|
Safety and tolerability of XL147 in combination with trastuzumab and in combination with trastuzumab and paclitaxel
時間枠:safety assessments at weekly study visits
|
safety assessments at weekly study visits
|
In Phase 1, the maximum tolerated dose (MTD) of XL147 when administered in combination with trastuzumab and in combination with trastuzumab and paclitaxel
時間枠:assessed by weekly study visits
|
assessed by weekly study visits
|
In Phase 2, objective tumor response
時間枠:every 6 weeks
|
every 6 weeks
|
二次結果の測定
結果測定 |
時間枠 |
---|---|
Duration of response and progression-free survival (Phase 2)
時間枠:every 6 weeks
|
every 6 weeks
|
Pharmacokinetics and pharmacodynamics of XL147 and trastuzumab when given in combination, and of XL147, trastuzumab, and paclitaxel when given in combination
時間枠:assessed weekly, then every 3 weeks
|
assessed weekly, then every 3 weeks
|
協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
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 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
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
- ARD11439
- XL147-203 (その他の識別子:(other study code))
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。
乳がんの臨床試験
-
Tianjin Medical University Cancer Institute and...Guangxi Medical University; Sun Yat-sen University; Chinese PLA General Hospital; The First Affiliated... と他の協力者完了
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI); Highlight Therapeutics積極的、募集していない平滑筋肉腫 | 悪性末梢神経鞘腫瘍 | 滑膜肉腫 | 未分化多形肉腫 | 骨の未分化高悪性度多形肉腫 | 粘液線維肉腫 | II期の体幹および四肢の軟部肉腫 AJCC v8 | III期の体幹および四肢の軟部肉腫 AJCC v8 | IIIA 期の体幹および四肢の軟部肉腫 AJCC v8 | IIIB 期の体幹および四肢の軟部肉腫 AJCC v8 | 切除可能な軟部肉腫 | 多形性横紋筋肉腫 | 切除可能な脱分化型脂肪肉腫 | 切除可能な未分化多形肉腫 | 軟部組織線維肉腫 | 紡錘細胞肉腫 | ステージ I 後腹膜肉腫 AJCC (American Joint Committee on Cancer) v8 | 体幹および四肢の I 期軟部肉腫 AJCC v8 | ステージ... およびその他の条件アメリカ
XL147 (SAR245408)の臨床試験
-
Sanofi完了