A Randomized Phase II Trial of Sacituzumab Govitecan (SG) and Bevacizumab Versus Standard of Care Carboplatin, Pegylated Liposomal Doxorubicin (PLD) and Bevacizumab in Patients With Platinum-Sensitive Ovarian Cancer That Has Progressed on Prior Maintenance PARP Inhibitor Therapy
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 87
- 主要终点
- Progression-free survival
研究概览
简要总结
This phase II trial compares the effect of sacituzumab govitecan and bevacizumab to standard care (carboplatin, pegylated liposomal doxorubicin, and bevacizumab) in patients with ovarian cancer that has come back after an initial response to platinum therapy (platinum-sensitive), that has progressed after poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor maintenance therapy (recurrent), and that has a mutation in the BRCA1 or BRCA2 genes or is homologous recombination deficient. Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a drug called govitecan. Sacituzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as TROP2 receptors, and delivers govitecan to kill them. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Liposomal doxorubicin is a form of the anticancer drug doxorubicin that is contained inside very tiny, fat-like particles. Liposomal doxorubicin may have fewer side effects and work better than other forms of the drug. Giving sacituzumab govitecan and bevacizumab may kill more tumor cells than standard care (carboplatin, pegylated liposomal doxorubicin, and bevacizumab) in patients with recurrent platinum-sensitive ovarian cancers that have BRCA1/2 mutations or homologous recombination deficiency.
详细描述
PRIMARY OBJECTIVE:
I. To assess the clinical activity of sacituzumab govitecan (sacituzumab govitecan-hziy [SG]) and bevacizumab (or an anti-VEGF antibody biosimilar) compared to standard of care carboplatin, pegylated liposomal doxorubicin hydrochloride (pegylated liposomal doxorubicin [PLD]) and bevacizumab (or an anti-VEGF antibody biosimilar), as measured by progression-free survival, in patients with platinum-sensitive ovarian cancer that has progressed while receiving first-line PARP inhibitor maintenance therapy.
SECONDARY OBJECTIVES:
I. To assess additional measures of clinical activity, including overall response rate and duration of response, of SG and bevacizumab compared to standard of care carboplatin, PLD and bevacizumab in patients with recurrent platinum-sensitive ovarian cancer.
II. To assess the safety of SG and bevacizumab in patients with recurrent platinum-sensitive ovarian cancer.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologic diagnosis of high grade serious or endometrioid epithelial ovarian cancer
- •Ovarian cancer = fallopian tube, ovarian, and primary peritoneal cancer
- •Disease must be platinum sensitive, as defined by progression documented ≥ 6 months (182 days) from the last receipt of platinum
- •Disease must have progressed during first line maintenance PARP inhibitor (PARPi) for advanced ovarian cancer. NO intervening therapies between progression on PARPi and study registration are permitted
- •Disease must be germline or somatic BRCA1 or BRCA2 mutated or homologous recombination deficiency test positive
- •Disease must be measurable or assessable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1
- •Patients with treated brain metastases are eligible if follow up brain imaging 4 weeks after central nervous system (CNS) directed therapy shows no evidence of progression
- •Secondary or cytoreductive surgery, after start of treatment on this trial, and prior to documentation of disease progression, is NOT permitted
- •No previous receipt of any topoisomerase-I inhibiting agents
- •No investigational agents within 4 weeks of study registration
- •No current treatment with any other (non-study) cytotoxic chemotherapy, targeted therapy, biologic therapy, immunotherapy or endocrine therapy for the treatment of the disease under the current study
- •Last dose of PARP inhibitor treatment must be ≥ 3 weeks before study registration
- •Patients with treated brain metastases are eligible if follow-up brain imaging after CNS-directed therapy shows no evidence of disease progression. Patients with brain metastases must have follow up imaging demonstrating no evidence of disease progression and that the disease is stable off of steroids
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- •Not pregnant and not nursing
- •Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3
- •Platelets ≥ 100,000 cells/mm^3
- •Hemoglobin ≥ 9 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] ≥ 9 g/dl is acceptable)
- •Creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula
- •Urinalysis with ≤ 1+ protein and/or urine protein < 1.0 g/24 hours (hrs)
- •Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN
- •Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better
- •No active infection requiring parenteral antibiotics
- •No non-healing wound, ulcer, or bone fracture
- •No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube
- •No clinically significant bleeding within 28 days prior to registration
- •No uncontrolled hypertension, defined as systolic ≥ 160 mm Hg or diastolic ≥ 100 mm Hg
- •Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the following exceptions:
- •Participants with grade 2 or lower neuropathy, any grade alopecia, well controlled hypertension, thyroid disease controlled with therapy, and history of thromboembolic disease on anticoagulation are eligible
- •Participants with laboratory-based grade 2 or higher adverse events (AEs) that meet the criteria outlined above are eligible
- •No major surgery within 3 weeks prior to study entry
- •Patients who underwent major surgery must have recovered adequately from any toxicity and/or complications from surgery prior to starting therapy
- •No strong inhibitors or inducers of UGT1A1
- •No history of allergic reaction to the study agent(s), compounds of similar chemical or biologic composition to the study agent(s) (or any of its excipients)
排除标准
- 未提供
研究组 & 干预措施
Arm II (SG, bevacizumab)
Patients receive SG IV on days 1 and 8 and bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Arm II (SG, bevacizumab)
Patients receive SG IV on days 1 and 8 and bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Bevacizumab (Biological)
Arm II (SG, bevacizumab)
Patients receive SG IV on days 1 and 8 and bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Computed Tomography (Procedure)
Arm I (carboplatin, PLD, bevacizumab)
Patients receive carboplatin IV on day 1, PLD IV on day 1 (or gemcitabine IV on days 1 and 8), and bevacizumab (or anti-VEGF antibody biosimilar) IV on days 1 and 15 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo ECHO at screening and undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Anti-VEGF Monoclonal Antibody (Biological)
Arm I (carboplatin, PLD, bevacizumab)
Patients receive carboplatin IV on day 1, PLD IV on day 1 (or gemcitabine IV on days 1 and 8), and bevacizumab (or anti-VEGF antibody biosimilar) IV on days 1 and 15 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo ECHO at screening and undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Carboplatin (Drug)
Arm II (SG, bevacizumab)
Patients receive SG IV on days 1 and 8 and bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm I (carboplatin, PLD, bevacizumab)
Patients receive carboplatin IV on day 1, PLD IV on day 1 (or gemcitabine IV on days 1 and 8), and bevacizumab (or anti-VEGF antibody biosimilar) IV on days 1 and 15 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo ECHO at screening and undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm I (carboplatin, PLD, bevacizumab)
Patients receive carboplatin IV on day 1, PLD IV on day 1 (or gemcitabine IV on days 1 and 8), and bevacizumab (or anti-VEGF antibody biosimilar) IV on days 1 and 15 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo ECHO at screening and undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Computed Tomography (Procedure)
Arm I (carboplatin, PLD, bevacizumab)
Patients receive carboplatin IV on day 1, PLD IV on day 1 (or gemcitabine IV on days 1 and 8), and bevacizumab (or anti-VEGF antibody biosimilar) IV on days 1 and 15 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo ECHO at screening and undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Echocardiography Test (Procedure)
Arm I (carboplatin, PLD, bevacizumab)
Patients receive carboplatin IV on day 1, PLD IV on day 1 (or gemcitabine IV on days 1 and 8), and bevacizumab (or anti-VEGF antibody biosimilar) IV on days 1 and 15 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo ECHO at screening and undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Pegylated Liposomal Doxorubicin Hydrochloride (Drug)
Arm II (SG, bevacizumab)
Patients receive SG IV on days 1 and 8 and bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Sacituzumab Govitecan (Biological)
Arm II (SG, bevacizumab)
Patients receive SG IV on days 1 and 8 and bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Anti-VEGF Monoclonal Antibody (Biological)
Arm I (carboplatin, PLD, bevacizumab)
Patients receive carboplatin IV on day 1, PLD IV on day 1 (or gemcitabine IV on days 1 and 8), and bevacizumab (or anti-VEGF antibody biosimilar) IV on days 1 and 15 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo ECHO at screening and undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Arm I (carboplatin, PLD, bevacizumab)
Patients receive carboplatin IV on day 1, PLD IV on day 1 (or gemcitabine IV on days 1 and 8), and bevacizumab (or anti-VEGF antibody biosimilar) IV on days 1 and 15 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo ECHO at screening and undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Gemcitabine (Drug)
Arm I (carboplatin, PLD, bevacizumab)
Patients receive carboplatin IV on day 1, PLD IV on day 1 (or gemcitabine IV on days 1 and 8), and bevacizumab (or anti-VEGF antibody biosimilar) IV on days 1 and 15 of each cycle. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. After 6-10 cycles, patients proceed to maintenance therapy.
MAINTENANCE: Patients receive bevacizumab (or anti-VEGF antibody biosimilar) IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo ECHO at screening and undergo CT and/or MRI and collection of blood samples throughout the trial.
干预措施: Bevacizumab (Biological)
结局指标
主要结局
Progression-free survival
时间窗: From randomization to either progressive disease or death from any cause, assessed up to 5 years
The primary analysis will compare progression-free survival between Arm II and Arm I using a stratified log-rank test. The corresponding hazard ratio will be estimated from a stratified Cox regression model. The treatment hazard ratio estimate and its 95% confidence interval will be estimated using proportional hazards models specified to be consistent with the logrank tests.
次要结局
- Objective response rate (ORR)(Within 12 months of starting maintenance therapy)
- Duration of response (DOR)(From the first documented response (CR or PR) until disease progression or death, assessed up to 5 years)
- Incidence of adverse events(Up to 5 years)