Randomized Phase III Study of Oral Cyclophosphamide vs Doxorubicin in 65 Years or Older Patients With Advanced or Metastatic Soft Tissue Sarcoma: a UNICANCER/GERICO Multicenter Program
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- UNICANCER
- 入组人数
- 214
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
Most advanced or metastatic soft tissue sarcoma (STS) are unfortunately incurable, making the preservation of the patient's quality of life a major goal, along with prolonging survival.
Age is not a criterion for not providing effective treatment, but the goals of treatment change with age and must be integrated into the treatment decision. Elderly patients prioritise a life free of dependency, preservation of their cognitive functions and quality of life related to their state of health. They are therefore reluctant to receive a treatment that does little to improve life expectancy at the cost of significant functional losses.
Patients aged 65 years and older account for one third of all patients with STS. In the absence of dedicated recommendations, these elderly patients are currently receiving doxorubicin-based chemotherapy as first-line treatment (as recommended for younger patients), with a substantial risk of toxicity (especially cardiac). In this specific population, previous studies have shown that oral cyclophosphamide seems to have a promising activity, but also a very acceptable toxicity.
Thus, the GERICO study aims to compare standard doxorubicin chemotherapy with oral cyclophosphamide for the treatment of elderly patients with STS.
详细描述
Co-morbidities increase in number and severity with age, competing with cancer prognosis and making prioritizing medical issues necessary. Individualization of cancer treatment by integrating a comprehensive geriatric assessment (CGA) is frequently considered as essential and mandatory for elderly cancer patients. The G8 questionnaire is able to identify patients requiring CGA, with a threshold score of ≤14/17 and with a strong 1-year prognostic value.
According to guidelines, the recommended first-line treatment of these patients relies on single agent chemotherapy with anthracyclines (including doxorubicin); however, anthracycline-based treatments have modest performance in patients with metastatic STS with a median progression-free survival of about 4 months and an overall survival of about 12 months.
Previous studies have demonstrated promising activity of oral metronomic cyclophosphamide in STS patients and its favorable safety profile.
To evaluate this promising activity we designed a phase III, randomized, open-label, multicentric study comparing daily oral cyclophosphamide versus standard 3-week intravenous injection of doxorubicin in 65 years or older patients with advanced or metastatic STS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Previous systemic treatment for advance or metastatic sarcoma
- •Previous neoadjuvant or adjuvant anthracycline treatment for localized sarcoma
- •Soft-tissue sarcoma with the following histological subtypes: dermatofibrosarcoma protuberans, desmoid tumor, alveolar or embryonal rhabdomyosarcoma, Desmoplastic small round cell tumor, Kaposi Sarcoma, Gastro-Intestinal stromal tumor, Peripheral neuroectodermal tumors
- •Primary bone sarcoma (including osteosarcoma, Ewing tumor, chondrosarcoma, and chordoma)
- •Symptomatic or known central nervous system (CNS) metastases
- •Known history of or concomitant malignancy likely to affect life expectancy in the judgment of the investigator and history of radiotherapy mediastinal in the last five years
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before Day 1 of treatment
- •Active cardio vascular disease including any of the following: Congestive heart failure (New York Heart Association (NYHA) ≥Class 2), unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), acute inflammatory cardiopathy, severe arrythmia, high risk of bleeding, cerebrovascular accident within the last 6 months
- •Uncontrolled grade >2 hypertension. (Systolic blood pressure ≥160 mmHg or diastolic pressure ≥100 mmHg despite optimal medical management)
- •Ongoing infection ≥Grade 2 according to NCI Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)
- •Known history of human immunodeficiency virus (HIV) infection
- •Known history of chronic hepatitis B or C
- •History of organ allograft
- •Pre-existing acute hemorrhagic cystitis, urinary tract obstruction, acute urinary tract infection
- •Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
- •Substance abuse, medical condition, that may interfere with the patient's participation in the study or evaluation of the study results
- •Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation
- •Inability to swallow oral medications, any malabsorption condition.
- •Persons deprived of their liberty or under protective custody or guardianship
- •Participation in another therapeutic trial within the 30 days prior to randomization and during the study
- •Patients having received live attenuated vaccine therapy used for prevention of diseases as influenza, chickenpox, zoster, measles, mumps, rubella, tuberculosis, rotavirus or yellow fever within 4 weeks of the first dose of study drug. These vaccinations are not permitted during the study up to 6 months after the last treatment
- •Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons
研究组 & 干预措施
Doxorubicin
Intravenous Doxorubicin 60 mg/m² Cycle 1 then 75 mg/m² Cycle 2 to Cycle 6 D1-D21 with granulocyte-colony stimulating factor (G-CSF) and dexrazoxane.
干预措施: Doxorubicin (Drug)
Cyclophosphamide
Cyclophosphamide per os 100 mg twice a day, 1 week on, 1 week off until 2 years, or unacceptable toxicity, disease progression, withdrawn of consent or death.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: From randomization to disease progression or death, up to 2 years.
The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.
次要结局
- Overall survival (OS)(From randomization to death from any cause, up to 2 years)
- Assessment of the toxicity profile of oral cyclophosphamide and doxorubicin, as per NCI CTCAE v5.0(From randomization to progression, death or new treatment, up to 2 years.)
- Assessment of compliance to oral metronomic cyclophosphamide (Cyclophosphamide Arm only)(From randomization to the end of treatment, up to 2 years.)
- Best response under treatment(From randomization to progression, death or new treatment, up to 2 years.)
- Quality of life questionnaire - Core 30 (QLQ-C30)(At baseline, week 9, week 18, 3 months, 6 months, 9 months, 12 months, 15 month, 18 month, and 24 months)
- Quality of life questionnaire - Elderly cancer patients (QLQ-ELD14)(At baseline, week 9, week 18, 3 months, 6 months, 9 months, 12 months, 15 month, 18 month, and 24 months)
- Geriatric assessment(At baseline)