2023-503627-26-00进行中（未招募）2 期
Phase II trial of trastuzumab deruxtecan in first-line treatment HER2-positive locally advanced or metastatic breast cancer (MBC) patients considered resistant to trastuzumab + pertuzumab + taxane due to early relapse. “TRANSCENDER Study”
Grupo Espanol De Investigacion En Cancer De Mama19 个研究点 分布在 1 个国家目标入组 41 人开始时间: 2023年8月18日最近更新:
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 41
- 试验地点
- 19
- 主要终点
- Objective Response Rate (ORR) is defined as the rate of complete response (CR) plus partial response (PR) based on the investigator’s assessment using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1., out of the patients who received at least 1 dose of treatment.
研究概览
简要总结
To evaluate the antitumor activity of T-DXd in the first-line treatment of HER2-positive breast cancer patients resistant to trastuzumab-pertuzumab based therapy.
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Single Arm
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Written and signed informed consent obtained prior to any study-specific procedure
- •Left ventricular ejection fraction (LVEF) ≥ 50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
- •Adequate organ and marrow function defined as follows: a. Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 (1.5x109/L). b. Platelet count ≥ 100,000/mm3 (100x109/L). c. Hemoglobin ≥ 9g/dL (90g/L). d. Creatinine clearance ≥ 30 mL/min as calculated using the standard method for the institution. e. Total serum bilirubin ≤ 1.5 × ULN if no liver metastases or < 3 × ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline. f. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 3.0 x ULN (< 5.0 × ULN in participants with liver metastases). g. Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5.0 x ULN if bone or liver metastases are present). h. Serum albumin ≥ 2.5 g/dL
- •International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN.
- •Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
- •Negative serum pregnancy test with a sensitivity of at least 25 mIU/mL (unless permanent previous sterilization procedure such as bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) for premenopausal women, and for women who have experienced menopause onset < 12 months prior to first dose of therapy.
- •Male or female patients of at least 18 years of age.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤
- •Life expectancy ≥ 12 weeks
- •Recurrent breast cancer that is unresectable locally advanced or metastatic
- •Pathologically documented HER2-positive status by local laboratory determination, preferably on the most recent available FFPE tumor sample, according to the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) international guidelines valid at the time of the assay. In case of discordance in HER2 status in different biopsies, the result from the most recent biopsy will be used.
- •Pathologically documented Hormone Receptor (HR)-positive or -negative by local laboratory determination, preferably on the most recent available FFPE tumor sample, and according to ASCO/CAP international guidelines valid at the time of the assay. In case of discordance in HR status in different biopsies, the result from the most recent biopsy will be used.
- •Prior anti-HER2 based therapy (with trastuzumab plus pertuzumab plus taxane with or without trastuzumab-emtansine [T-DM1]) in the (neo)adjuvant setting with a relapse while on therapy or within 12 months from the end of last anti-HER2 therapy
- •Measurable disease assessed by the investigator based on RECIST version 1.1.
排除标准
- •Prior chemotherapy or HER2-targeted therapy for locally advanced or MBC (one prior endocrine therapy regimen for MBC without concurrent anti-HER2 therapy or radiotherapy is allowed).
- •Have a diagnosis of any other malignancy within 3 years prior to inclusion, except for adequately resected non-melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated and contralateral breast cancer.
- •Receipt of live, attenuated vaccine within 30 days prior to the first dose of T-DXd.
- •Prior treatment with T-DXd or allergic reaction to trastuzumab
- •Patient is pregnant or breastfeeding or planning to become pregnant within the projected duration of the trial, starting at screening and through 7 months after the last dose of the study treatment. Male patients whose partners plan to become pregnant within the duration of the trial, starting at screening and through 4 months after the last dose of the study treatment. ✓ For premenopausal women it is necessary an agreement to remain complete abstinent or use single or combined non-hormonal contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose of study treatment. Examples of non-hormonal contraceptive methods with a failure rate of < 1% per year include bilateral tubal litigation, male sterilization, and certain intrauterine devices (provided coils are copper banded). ▪ Alternative, two methods (e.g. two barrier methods such as a condom and a cervical cap or combined with estrogen and progestogen) may be combined to achieve a failure rate of < 1% per year. Barrier methods must always be supplemented with the use of a spermicide. Female patients must not donate, or retrieve for their own use, ova from the time of enrollment and throughout the study treatment period, and for at least 7 months after the final study drug administration. They should refrain from breastfeeding throughout this time. Preservation of ova may be considered prior to enrollment in this study. ✓ For men it is necessary an agreement to remain complete abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and to refrain from donating sperm during the same period, as defined below with female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 4 months after the last dose of study treatment to avoid exposing the embryo. Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
- •Uncontrolled intercurrent illness including uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.
- •Has substance abuse or any other medical/psychological conditions that may, in the opinion of the investigator, interfere with the patient’s participation in the clinical study or evaluation of the clinical study results.
- •Ineligible for treatment with T-DXd.
- •Any substance abuse or other medical conditions that, in the investigator's opinion, may interfere with patient's participation or study results.
- •Patients with spinal cord compression, leptomeningeal disease or clinically active central nervous system (CNS) metastases. Participants with clinically inactive brain metastases or treated brain metastases that are no longer symptomatic, and no needing corticosteroids or anticonvulsants may be enrolled in the study.
- •Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- •Lung criteria: a. Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within three months of the study enrollment, severe asthma, severe Chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion etc.). b. Any autoimmune, connective tissue or inflammatory disorders (e.g. Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the electronic Case Report Form (eCRF) for patients who are enrolled in the study. c. Prior pneumonectomy.
- •Medical history of myocardial infarction within 6 months before registration, symptomatic congestive heart failure (CHF), troponin levels consistent with myocardial infarction as defined according to American College of Cardiologists (ACC) guidelines, unstable angina, or serious cardiac arrhythmia requiring treatment. QT interval corrected using Fridericia’s formula (QTcF) > 470 msec (females) or > 450 msec (males) based on average of the screening triplicate 12-lead ECG.
- •History of active primary immunodeficiency, known Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
- •Patients who received before treatment starts:a. Any investigational agent within 4 weeks. b. Chemotherapy within a period of time that is shorter than the cycle duration used for that treatment (e.g. < 3 weeks for fluorouracil, doxorubicine, epirubicine or < 1 week for weekly chemotherapy). c. Targeted therapy (e.g., antibodies): up to 4 weeks prior to starting study treatment. d. Endocrine therapy: tamoxifen or aromatase inhibitor within 2 weeks prior to starting study treatment. e. Radiotherapy within 2 weeks prior to starting study treatment. Patients who received prior radiotherapy to >25% of bone marrow are not eligible regardless of when it was administered. f. Major surgery or other anti-cancer therapy not previously specified within 4 weeks prior to starting study treatment. In any case, resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI-CTCAE version 5.0 grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator´s discretion) is mandatory.Patients may be enrolled with chronic, stable grade 2 toxicities (defined as no worsening to > grade 2 for at least 3 months prior to enrollment and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, such as: chemotherapy-induced neuropathy or fatigue and immunotherapy-induced toxicities (e.g. endocrinopathies as hypothyroidism/hyperthyroidism, type 1 diabetes, hypoglycemia, adrenal insufficiency, adrenalitis and skin hypopigmentation [vitiligo]).
结局指标
主要结局
Objective Response Rate (ORR) is defined as the rate of complete response (CR) plus partial response (PR) based on the investigator’s assessment using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1., out of the patients who received at least 1 dose of treatment.
Objective Response Rate (ORR) is defined as the rate of complete response (CR) plus partial response (PR) based on the investigator’s assessment using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1., out of the patients who received at least 1 dose of treatment.
次要结局
- Other efficacy endpoints: Progression-Free Survival (PFS) is defined as the time from the date of enrollment to the date of disease progression, based on the investigator’s assessment using RECIST version 1.1., or death from any cause, whichever occurs first.
- Other efficacy endpoints: Overall Survival (OS) is defined as the time from the date of enrollment to the date of death from any cause.
- Other efficacy endpoints: Time to treatment response (TTR) is defined as the time from the date of enrollment to the date of first documentation of objective tumor response (CR or PR).
- Other efficacy endpoints: Duration of response (DoR) is defined as the time from the date of first documentation of objective tumor response (CR or PR) to the date of first documented progressive disease based on the investigator’s assessment using RECIST version 1.1., or death from any cause, whichever occurs first.
- Safety: Incidence and severity of Adverse Events (AEs) and clinical lab abnormalities. AEs grades will be defined by the National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 5.0. AE terms will be coded according to the MedDRA dictionary.
- Tolerability: Incidence of T-DXd dose modifications, discontinuations due to AEs, number of administered cycles, dose intensity, etc.
- Changes (mean score) and time to deterioration on EORTC QLQ-C30 Global Health Status/QoL from baseline.
研究者
Clinical Operations Department
Scientific
Grupo Espanol De Investigacion En Cancer De Mama
研究点 (19)
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