Fulvestrant (F)+Placebo vs F+Palbociclib First Line for Postmenopausal Hormone Receptor+ Advanced Breast Cancer (FLIPPER)
Phase II Study to Compare Fulvestrant (F) 500mg Plus Placebo vs F 500mg Plus Palbociclib as First Line Treatment for Postmenopausal Women With Hormone Receptor Positive Advanced Breast Cancer Sensitive to Endocrine Therapy. GEICAM/2014-12
調査の概要
詳細な説明
Patients must have at least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline and is suitable for repeated assessment by CT, MRI or plan x-ray. Patients with bone-only disease must have a lytic or mixed (lytic + blastic) lesion, which has not been previously irradiated and can be accurately assessed by CT/MRI or x-ray. Approximately 190 patients will be randomized 1:1 between the experimental arm (approximately 95 patients treated with fulvestrant plus palbociclib) and the control arm (approximately 95 patients treated with fulvestrant plus placebo).
Primary Objective:
• To compare the efficacy of fulvestrant in combination with palbociclib versus fulvestrant plus placebo in terms of the rate of Progression-Free Survival (PFS) at 1 year in postmenopausal women with HR-positive/HER2-negative metastatic breast cancer previously treated with endocrine therapy for at least 5 years and remaining disease free for more than 12 months following its completion or have "de novo" metastatic disease
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
-
-
-
Cork、アイルランド
- Bon Secours Hospital
-
Dublin、アイルランド
- Beaumont Hospital
-
Dublin、アイルランド
- Mater Misericordiae University Hospital
-
Galway、アイルランド
- Galway University Hospital
-
Waterford、アイルランド
- University Hospital Waterford
-
-
-
-
-
A Coruña、スペイン、15009
- Centro Oncologico de Galicia
-
Barcelona、スペイン、08003
- Hospital del Mar
-
Barcelona、スペイン、08916
- Hospital Universitario Germans Trias i Pujol
-
Barcelona、スペイン、08026
- Hospital de la Santa Creu y Sant Pau
-
Córdoba、スペイン、14004
- Hospital Universitario Reina Sofia
-
Jaen、スペイン、23007
- Complejo Hospitalario de Jaén
-
Leon、スペイン、24080
- Complejo Asistencial Universitario de León
-
Madrid、スペイン、28034
- Hospital Universitario Ramón y Cajal
-
Madrid、スペイン、28040
- Hospital Clínico Universitario San Carlos
-
Madrid、スペイン、28492
- Hospital Universitario de Fuenlabrada
-
Málaga、スペイン、29011
- Hospital Regional Universitario de Málaga
-
Sevilla、スペイン、41013
- Hospital Universitario Virgen del Rocio
-
Sevilla、スペイン、41009
- Hospital Universitario Virgen De La Macarena
-
Sevilla、スペイン、41014
- Hospital Universitario de Valme
-
Sevilla、スペイン、41013
- Hospital Quirón Sagrado Corazón de Sevilla
-
Valencia、スペイン、46010
- Hospital Clinico Universitario De Valencia
-
Valencia、スペイン、46014
- Hospital General Universitario Valencia
-
Valencia、スペイン、46026
- Hospital Universitario i Politecnic la Fe
-
Zaragoza、スペイン、50009
- Hospital Universitario Miguel Servet
-
-
Asturias
-
Oviedo、Asturias、スペイン、33011
- Hospital Universitario Central de Asturias
-
-
Baleares
-
Palma De Mallorca、Baleares、スペイン、07198
- Hospital Son Llàtzer
-
Palma de Mallorca、Baleares、スペイン、07120
- Hospital Universitari Son Espases
-
-
Barcelona
-
Terrassa、Barcelona、スペイン、08221
- Hospital Universitario Mútua Terrassa
-
-
Madrid
-
Parla、Madrid、スペイン、28981
- Hospital Universitario Infanta Cristina
-
Pozuelo de Alarcón、Madrid、スペイン、28223
- Hospital Universitario Quiron de Madrid
-
-
Pontevedra
-
Vigo、Pontevedra、スペイン、36204
- Complejo Hospitalario Universitario Vigo
-
-
Tarragona
-
Reus、Tarragona、スペイン、43204
- Hospital Universitario Sant Joan Reus
-
-
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 patient has signed and dated the informed consent document and it has been obtained before conducting any procedure specifically for the study.
- Availability of a tumor tissue sample, archival (primary tumour) or from the metastatic lesions (preferable) for the central ER, PgR and HER2 testing.
- Histological/cytological confirmation of breast cancer with evidence of metastatic disease (loco-regional or distant), not amenable to resection or radiation therapy with curative intent.
- Documented positive hormone receptor status (> or = 1% of tumour cells with oestrogen receptor [ER] and/or progesterone receptor [PgR] expression) based on central testing on the most recent tumour biopsy.
- Documented HER2-negative tumour based on central testing on the most recent tumour biopsy. HER2-negative tumour is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (FISH/CISH/SISH) defined as a HER2/CEP17 ratio <2 or for single probe assessment a HER2 copy number <4.
- Patients must have received at least 5 years of endocrine therapy in the adjuvant setting as treatment for early disease and remained disease free for more than 12 months following its completion or have "de novo" metastatic disease. Patients that have been scheduled 5 years with adjuvant endocrine therapy and stopped treatment, by patient's own decision, after completing at least 3 years of treatment, can be also be included as long as they have remained free of disease 3 years after discontinuing the endocrine therapy.
- Patients must have at least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline and is suitable for repeated assessment by CT, MRI, plan x-ray or physical examination. Clinical lesions will only be considered measurable when they are superficial and ≥10mm diameter as assessed using callipers (e.g. skin nodules). Patients with bone-only disease must have a lytic or mixed (lytic + blastic) lesion, which has not been previously irradiated and can be accurately assessed by CT/MRI according to RECIST version 1.1.
Postmenopausal patient, defined as a woman fulfilling any one of the following criteria (based on the NCCN definition of menopause [National Comprehensive Cancer Network 2008]):
- Prior bilateral oophorectomy.
- Age > 60 years.
- Age ≤ 60 years and with amenorrhea for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and follicle stimulating hormone and estradiol in the postmenopausal range.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2.
- At least 18 years of age.
- Life expectancy ≥ 12 weeks.
Adequate organ and bone marrow function:
- ANC ≥ 1,500/mm3 (1.5x109/L);
- Platelets ≥ 100,000/mm3 (100x109/L);
- Haemoglobin (Hgb) ≥ 9g/dL (90g/L);
- Serum creatinine ≤ 1.5xUpper Limit of Normal (ULN) or estimated creatinine clearance ≥ 60ml/min as calculated using the method standard for the institution;
- Total serum bilirubin ≤ 1.5xULN (<3xULN if Gilbert´s disease);
- AST and/or ALT ≤ 3xULN (≤5xULN if liver metastases present);
- Alkaline Phosphatase (AP) ≤ 2.5xULN (≤5xULN if bone or liver metastases present).
- Patients consent to biological sample provision for biomarker exploratory analysis.
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Exclusion Criteria:
- Prior systemic therapy for metastatic disease. Note: patients with a local recurrent disease treated with surgery (R0) and receiving a "second hormonal adjuvant therapy for five years" will be allowed, provided they have remained disease free for more than 12 months following its completion.
- Have "de novo" locally advanced disease.
- Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be potent CYP3A4 inducers, and drugs that are known to prolong the QT interval.
- Presence of life-threatening metastatic visceral disease, defined as extensive hepatic involvement, or any degree of brain or leptomeningeal involvement (past or present), or symptomatic pulmonary lymphangitis spread, or any known bone marrow infiltration due to breast cancer. Patients with discrete pulmonary parenchymal metastases are eligible, provided their respiratory function is not significantly compromised as a result of disease.
- Treatment with a non-approved or experimental drug within 4 weeks before randomization.
- Prior treatment with any CDK4/6 inhibitor or fulvestrant.
- Current or prior malignancy within previous 5 years (other than breast cancer or adequately treated basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix).
History of:
- Bleeding diathesis (i.e., disseminated intravascular coagulation [DIC], clotting factor deficiency) or long-term (>6 months) anticoagulant therapy (other than antiplatelet therapy and low dose coumarin derivatives provided that the International Normalised Ratio (INR) is less than 1.6). Hypersensitivity to active or inactive excipients of fulvestrant, palbociclib/placebo or castor oil.
- Any severe concomitant condition which makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the trial protocol, e.g. uncontrolled cardiac disease or uncontrolled diabetes mellitus.
- QTc interval > 480msec, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
- Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (eg, hypocalcaemia, hypokalaemia, hypomagnesaemia).
- Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of palbociclib, such as history of GI surgery which may result in intestinal blind loops and patients with clinically significant gastro-paresis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease or diarrhoea of CTCAE grade > 1.
- Prior hematopoietic stem cell or bone marrow transplantation.
- Known human immunodeficiency virus infection.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
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:並列代入
- マスキング:トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:PD-0332991(Palbociclib)+fulvestrant(FaslodexTM)
Fulvestrant 500mg, on days 1, 15 (±3 days) of Cycle 1, and then on Day 1 of each subsequent 28 day cycle (±3 days) in combination with Palbociclib, 125 mg, orally once daily from day 1 to day 21 followed by 7 days off treatment on every 28 days cycles.
|
Palbociclib, 125 mg, orally once daily from day 1 to day 21 followed by 7 days off treatment on every 28 days cycles. Patients will continue to receive their assigned treatment until objective disease progression, clinical progression (under investigator criteria), unacceptable toxicity, death or withdrawal of consent, whichever occurs first
他の名前:
Fulvestrant 500mg, two 5ml intramuscular injections (one in each buttock), on days 1, 15 (±3 days) of Cycle 1, and then on Day 1 of each subsequent 28 day cycle (±3 days) Patients will continue to receive their assigned treatment until objective disease progression, clinical progression (under investigator criteria), unacceptable toxicity, death or withdrawal of consent, whichever occurs first
他の名前:
|
アクティブコンパレータ:Placebo+fulvestrant(FaslodexTM)
Fulvestrant 500mg on days 1, 15 (±3 days) of Cycle 1, and then on Day 1 of each subsequent 28 day cycle (±3 days) in combination with Placebo orally once daily from day 1 to day 21 followed by 7 days off treatment on every 28 days cycles.
|
Fulvestrant 500mg, two 5ml intramuscular injections (one in each buttock), on days 1, 15 (±3 days) of Cycle 1, and then on Day 1 of each subsequent 28 day cycle (±3 days) Patients will continue to receive their assigned treatment until objective disease progression, clinical progression (under investigator criteria), unacceptable toxicity, death or withdrawal of consent, whichever occurs first
他の名前:
Placebo orally once daily from day 1 to day 21 followed by 7 days off treatment on every 28 days cycles. Patients will continue to receive their assigned treatment until objective disease progression, clinical progression (under investigator criteria), unacceptable toxicity, death or withdrawal of consent, whichever occurs firs |
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 |
---|---|---|
Efficacy in terms of the rate of Progression-Free Survival (PFS)
時間枠:at 1 year
|
assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by the investigator
|
at 1 year
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Progression-Free Survival (PFS)
時間枠:an average of 40-44 months since FPFV (approximately Ago2019)
|
the time from the date of randomization to the first documented progressive disease, using RECIST version 1.1, or death from any cause, whichever occurs first
|
an average of 40-44 months since FPFV (approximately Ago2019)
|
Objective Response Rate (ORR)
時間枠:at 1 year and to be updated with further analyses
|
the percentage of patients with a complete or partial response out of the patients who had measurable disease at baseline.
|
at 1 year and to be updated with further analyses
|
Clinical Benefit Rate (CBR)
時間枠:at 1 year and to be updated with further analyses
|
Complete Response (CR) plus Partial Response (PR) plus stable disease (SD) lasting ≥ 24 weeks (+/- 2 weeks) according to RECIST version 1.1.
|
at 1 year and to be updated with further analyses
|
Overall Survival (OS).
時間枠:an average of 40-44 months since FPFV(approximately Ago2019). A formal analysis will be performed when at least 60% of patients have died (2021)
|
the time from the date of randomization to the date of death from any cause.
|
an average of 40-44 months since FPFV(approximately Ago2019). A formal analysis will be performed when at least 60% of patients have died (2021)
|
1 year and 2 year survival probabilities
時間枠:1 year and 2 year
|
the percentage of patients without death from any cause out of the randomised patients (calculated using the Kaplan-Meier technique).
|
1 year and 2 year
|
Incidence of adverse events occurring during the study, and their relatedness to the study drug/medications (safety and tolerability).
時間枠:at 1 year and to be updated with further analyses
|
Safety will be assessed by standard clinical and laboratory tests.
Adverse events will be graded according to NCI-CTCAE version 4.0
|
at 1 year and to be updated with further analyses
|
Patient reported outcomes of health-related quality of life based on EORTC QLQ-C30 Global Health Status/Quality of Life and Physical Function
時間枠:at 1 year and to be updated with further analyses
|
Generic aspects of quality of life will be assessed.
Changes (mean score) from baseline and time to deterioration will be analyzed.Health Status/QoL and Physical Function and EORTC QLQ-BR23 Breast Module from baseline
|
at 1 year and to be updated with further analyses
|
Patient reported outcomes of health-related quality of life based on EORTC QLQ-BR23 Breast Module.
時間枠:at 1 year and to be updated with further analyses
|
Disease-specific treatment measurements will be assessed.
Changes (mean score) from baseline and time to deterioration will be analyzed.
|
at 1 year and to be updated with further analyses
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Biomarker analyses
時間枠:Up to 5 years
|
Identify promising biomarkers of response to fulvestrant plus palbociclib and fulvestrant plus placebo.
|
Up to 5 years
|
協力者と研究者
協力者
捜査官
- スタディディレクター:Study Director、Hospital del Mar
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (予想される)
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 (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
- GEICAM/2014-12
- 2015-002437-21 (EudraCT番号)
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?
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。
乳房腫瘍の臨床試験
-
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
PD-0332991 (Palbociclib)の臨床試験
-
University of Texas Southwestern Medical CenterUniversity of Pennsylvania; Pfizer完了
-
National Cancer Institute (NCI)積極的、募集していない造血およびリンパ系細胞腫瘍 | 進行性リンパ腫 | 進行性悪性固形新生物 | 難治性リンパ腫 | 難治性悪性固形新生物アメリカ
-
National Cancer Institute (NCI)積極的、募集していない再発性小児上衣腫 | 進行性悪性固形新生物 | 再発ユーイング肉腫 | 再発性肝芽腫 | 再発性ランゲルハンス細胞組織球症 | 再発性悪性胚細胞腫瘍 | 再発性悪性神経膠腫 | 再発髄芽腫 | 再発神経芽腫 | 再発非ホジキンリンパ腫 | 再発性骨肉腫 | 再発性末梢原始神経外胚葉性腫瘍 | 再発ラブドイド腫瘍 | 再発横紋筋肉腫 | 再発性軟部肉腫 | 難治性上衣腫 | 難治性ユーイング肉腫 | 難治性肝芽腫 | 難治性ランゲルハンス細胞組織球症 | 難治性悪性胚細胞腫瘍 | 難治性悪性神経膠腫 | 難治性髄芽腫 | 難治性神経芽細胞腫 | 難治性非ホジキンリンパ腫 | 難治性骨肉腫 | 難治性末梢性原始神経外胚葉性腫瘍 | 難治性ラブドイド腫瘍 | 難治性横紋筋肉腫 | 難治性軟部肉腫 | 再発神経膠腫 | 難治性神経膠腫 | 再発腎ウィルムス腫瘍アメリカ, プエルトリコ
-
Roswell Park Cancer Institute引きこもった
-
Emory UniversityNational Cancer Institute (NCI)引きこもった予後 IV期乳がん AJCC v8 | 脳の転移性悪性新生物 | 転移性乳癌 | 解剖学的病期 IV 乳がん 米国がん合同委員会 (AJCC) v8
-
National Cancer Institute (NCI)積極的、募集していない