NCT06895733招募中1 期
A Multi Cohort Phase IB/II Clinical Study of Pazopanib Combined With Palbociclib for Third Line and Beyond Treatment of Refractory Solid Tumors With Co-amplified in the 11q13(FGF3/4/19/CCND1)
Tianjin Medical University Second Hospital1 个研究点 分布在 1 个国家目标入组 65 人开始时间: 2024年11月27日最近更新:
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The efficacy and safety of Pazopanib combined with Palbociclib in the third line and above treatment of refractory solid tumors co amplified in the 11q13 region (FGF3/4/19/CCND1).
详细描述
Based on literature review, this study first conducted a phase Ib study to observe the dose limiting toxicity (DLTs) of the combination therapy of pazopanib and palbociclib and to determine the recommended dose for phase II study (RP2D); Further phase II studies will be conducted to evaluate the efficacy of pazopanib combined with palbociclib in the third line and above treatment of refractory solid tumors co amplified in the 11q13 region using objective response rate (ORR) or progression free survival 2/progression free survival 1 (PFS2/PFS1). And observe and evaluate the progression free survival (PFS), time to remission (TTR), disease control rate (DCR), and overall survival (OS) of pazopanib combined with palbociclib for third line and above treatment of refractory solid tumors co amplified in the 11q13 region. Evaluate the safety of Pazopanib combined with palbociclib for the third line and above treatment of refractory solid tumors co amplified in the 11q13 region.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily join this study and sign an informed consent form;
- •≥ 18 years old;
- •Patients with metastatic solid tumors diagnosed by histology or cytology; Queue 1:11q13 co amplified or FGFR1/FGFR2 amplified urothelial carcinoma Queue 2: Head and neck squamous cell carcinoma co amplified in 11q13 region Queue 3:11q13 co amplified other solid tumors
- •Disease progression or intolerable toxicity confirmed by imaging during or after treatment with at least two standard treatment regimens in the past;
- •According to RECIST 1.1, there must be at least one measurable lesion;
- •Can swallow pills normally;
- •ECOG score: 0-2;
- •Expected survival period ≥ 12 weeks;
- •The function of important organs meets the following requirements (no blood components or cell growth factor drugs are allowed to be used within 14 days before the first medication):
- •Absolute neutrophil count ≥ 1.5 × 109/L; Platelets ≥ 100 × 109/L; Hemoglobin ≥ 90 g/L; Serum albumin ≥ 30 g/L; Serum total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN, and if there is liver metastasis, ALT and AST ≤ 5ULN; AKP≤ 2.5×ULN；Serum creatinine ≤ 1.5 × ULN; International normalized ratio (INR) ≤ 1.5 (not receiving anticoagulant therapy);
- •Non surgical sterilization or female patients of childbearing age are required to use a medically approved contraceptive measure (such as intrauterine device, contraceptive pill, or condom) during the study treatment period and within 3 months after the end of the study treatment period; Female patients of childbearing age who undergo non-surgical sterilization must have a negative serum or urine HCG test within 7 days prior to their first medication; And it must be during non lactation period; For male patients whose partners are women of childbearing age, effective contraception methods should be used during the trial period and within 3 months after the last administration of the trial drug.
排除标准
- •Known history or evidence of interstitial lung disease or active non infectious pneumonia;
- •Known to have central nervous system metastases;
- •Within the past 5 years or simultaneously with other malignant tumors (excluding cured skin basal cell carcinoma and cervical carcinoma in situ);
- •Suffering from hypertension and unable to achieve good control with antihypertensive medication (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg); Allow the above parameters to be achieved through the use of antihypertensive therapy; Previously experienced hypertensive crisis or hypertensive encephalopathy;
- •There are uncontrolled clinical symptoms or diseases of the heart, such as: (1) NYHA grade 2 or above heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, (5) QTc>450ms (male); QTc>470ms (female);
- •For those undergoing thrombolytic or anticoagulant therapy, prophylactic use of low-dose aspirin and low molecular weight heparin is allowed;
- •Within the first 3 months of enrollment, there have been significant clinical bleeding symptoms or clear bleeding tendencies; If fecal occult blood is positive during the baseline period, a follow-up examination can be conducted. If the result is still positive after the follow-up examination, gastroscopy examination is required;
- •Tumor invasion of important blood vessels, or the possibility of tumor invasion of important blood vessels in the future research period determined by imaging, may lead to fatal bleeding;
- •If the patient has pleural effusion, ascites, or pericardial effusion that requires drainage, and the researcher evaluates the symptoms to be stable after drainage, they can be enrolled;
- •Occurrence of arterial/venous thrombosis events within the first 6 months of enrollment, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
- •Known genetic or acquired bleeding and thrombophilia tendencies (such as in hemophilia patients, coagulation dysfunction, etc.);
- •Within 6 months prior to the start of treatment, there has been an abdominal fistula, gastrointestinal perforation, or abdominal abscess;
- •Significant vascular disease (such as aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) occurred within 6 months prior to the start of the study treatment;
- •Severe, unhealed, or cracked wounds, as well as active ulcers or untreated fractures;
- •Received major surgical treatment (excluding diagnosis) within 4 weeks before the start of the study treatment or expected to undergo major surgical treatment during the study period;
- •Urine routine shows that urine protein is ≥++and has been confirmed to have a 24-hour urine protein level>1.0 g;
- •Previously received radiotherapy (excluding palliative radiotherapy for bone lesions), chemotherapy, surgery (excluding biopsy), and less than 4 weeks before the first study medication after completion of treatment (last medication); The last dose of antibody administration is less than 4 weeks after the first study medication; Molecular targeted therapy (including other oral targeted drugs used in clinical trials) for patients with less than 5 drug half lives from the first study drug, or adverse reactions caused by previous treatment (excluding hair loss) that have not recovered to ≤ CTCAE grade 1;
- •Suffering from active infection, having unexplained fever ≥ 38.5 ℃ within 7 days before medication, or baseline white blood cell count>15 × 109/L;
- •Suffering from congenital or acquired immune dysfunction (such as HIV infected individuals); Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥ 2000 IU/ml, or hepatitis C virus antibody positive;
- •Previously received anti angiogenic therapy;
- •According to the researchers' judgment, the patient may have other factors that may affect the research results or cause the study to be terminated midway, such as alcohol abuse, drug abuse, other serious illnesses (including mental illnesses) that require concomitant treatment, serious laboratory test abnormalities, and family or social factors that may affect the patient's safety.
研究组 & 干预措施
Uroepithelial carcinoma
Experimental
Uroepithelial carcinoma with co-amplification of 11q13 region(FGF3/4/19/CCND1) or FGFR1/FGFR2 amplification
干预措施: Pazopanib Oral Tablet (Drug)
Uroepithelial carcinoma
Experimental
Uroepithelial carcinoma with co-amplification of 11q13 region(FGF3/4/19/CCND1) or FGFR1/FGFR2 amplification
干预措施: Palbociclib (Drug)
Head and neck squamous cell carcinoma
Experimental
Head and neck squamous cell carcinoma co-amplified in the 11q13 region(FGF3/4/19/CCND1)
干预措施: Pazopanib Oral Tablet (Drug)
Head and neck squamous cell carcinoma
Experimental
Head and neck squamous cell carcinoma co-amplified in the 11q13 region(FGF3/4/19/CCND1)
干预措施: Palbociclib (Drug)
Other solid carcinoma
Experimental
Other solid carcinoma co-amplified in the 11q13 region(FGF3/4/19/CCND1)
干预措施: Pazopanib Oral Tablet (Drug)
Other solid carcinoma
Experimental
Other solid carcinoma co-amplified in the 11q13 region(FGF3/4/19/CCND1)
干预措施: Palbociclib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Through study completion, an expected average of 1 year.
Objective Response Rate (ORR) assessed according to the evaluation criteria for the efficacy of solid tumors (RECIST v1.1) for cohort1 and cohort2.
PFS2/PFS1(Progression Free Survival 2/Progression Free Survival 1)
时间窗: Through study completion, an expected average of 1 year.
For cohort3,the time to progression-free survival during the substudy (PFS2) exceeds the documented time to disease progression-free survival during the last treatment prior to substudy entry (PFS1) by at least 35% (ie, PFS2/PFS1≥1.3) or, if PFS1 is not evaluable, time to progressive disease exceeds 6 months.
次要结局
- Progression Free Survival(PFS)(From treatment administration up to a maximum duration of 18 months)
- Overall Survival(OS)(From treatment administration up to a maximum duration of 18 months)
- Disease Control Rate (DCR)(From treatment administration up to a maximum duration of 18 months)
- Time to response (TTR)(From treatment administration up to a maximum duration of 18 months.)
- Percentage of Participants With Adverse Events (AEs)(From treatment administration up to a maximum duration of 18 months.)
研究者
研究点 (1)
Loading locations...
相似试验
进行中（未招募）
1 期
Pazopanib Pediatric Phase II Trial Children's Oncology Group in Solid TumorsRhabdomyosarcoma, non-rhabdomyosarcomatous soft tissue sarcoma (including synovial sarcoma, alveolar soft part sarcoma and desmoplastic small round cell tumor), Ewing sarcoma/peripheral Primitive Neuro Ectodermal Tumor (PNET), hepatoblastoma, neuroblastoma (measurable and evaluable), and osteosarcomaMedDRA version: 20.0 Level: HLT Classification code 10019825 Term: Hepatoblastomas System Organ Class: 100000005101MedDRA version: 20.0 Level: PT Classification code 10029260 Term: Neuroblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 15.1 Level: HLGT Classification code 10041299 Term: Soft tissue sarcomas System Organ Class: 100000004864MedDRA version: 20.0 Level: PT Classification code 10031291 Term: Osteosarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: HLT Classification code 10039023 Term: Rhabdomyosarcomas System Organ Class: 100000143528MedDRA version: 20.0 Level: PT Classification code 10015560 Term: Ewing's sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)EUCTR2013-003595-12-CZovartis Pharma Services AG154
进行中（未招募）
1 期
Pazopanib Pediatric Phase II Trial Children's Oncology Group in Solid TumorsRhabdomyosarcoma, non-rhabdomyosarcomatous soft tissue sarcoma (including synovial sarcoma, alveolar soft part sarcoma and desmoplastic small round cell tumor), Ewing sarcoma/peripheral Primitive Neuro Ectodermal Tumor (PNET), hepatoblastoma, neuroblastoma (measurable and evaluable), and osteosarcomaMedDRA version: 20.0 Level: HLT Classification code 10019825 Term: Hepatoblastomas System Organ Class: 100000005101MedDRA version: 20.0 Level: PT Classification code 10029260 Term: Neuroblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 15.1 Level: HLGT Classification code 10041299 Term: Soft tissue sarcomas System Organ Class: 100000004864MedDRA version: 20.0 Level: PT Classification code 10031291 Term: Osteosarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: HLT Classification code 10039023 Term: Rhabdomyosarcomas System Organ Class: 100000143528MedDRA version: 20.0 Level: PT Classification code 10015560 Term: Ewing's sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)EUCTR2013-003595-12-ESovartis Farmacéutica, S.A.154
进行中（未招募）
1 期
Pazopanib Pediatric Phase II Trial Children's Oncology Group in Solid TumorsRhabdomyosarcoma, non-rhabdomyosarcomatous soft tissue sarcoma (including synovial sarcoma, alveolar soft part sarcoma and desmoplastic small round cell tumor), Ewing sarcoma/peripheral Primitive Neuro Ectodermal Tumor (PNET), hepatoblastoma, neuroblastoma (measurable and evaluable), and osteosarcomaMedDRA version: 20.0Level: HLTClassification code 10019825Term: HepatoblastomasSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10029260Term: NeuroblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 15.1Level: HLGTClassification code 10041299Term: Soft tissue sarcomasSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10031291Term: OsteosarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: HLTClassification code 10039023Term: RhabdomyosarcomasSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10015560Term: Ewing's sarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)EUCTR2013-003595-12-FRovartis Pharma Services AG154
进行中（未招募）
1 期
Pazopanib Pediatric Phase II Trial Children's Oncology Group in Solid TumorsRhabdomyosarcoma, non-rhabdomyosarcomatous soft tissue sarcoma (including synovial sarcoma, alveolar soft part sarcoma and desmoplastic small round cell tumor), Ewing sarcoma/peripheral Primitive Neuro Ectodermal Tumor (PNET), hepatoblastoma, neuroblastoma (measurable and evaluable), and osteosarcomaMedDRA version: 20.0Level: HLTClassification code 10019825Term: HepatoblastomasSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10029260Term: NeuroblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 15.1Level: HLGTClassification code 10041299Term: Soft tissue sarcomasSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10031291Term: OsteosarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: HLTClassification code 10039023Term: RhabdomyosarcomasSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10015560Term: Ewing's sarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)EUCTR2013-003595-12-HUovartis Pharma Services AG154
进行中（未招募）
1 期
Pazopanib Pediatric Phase II Trial Children's Oncology Group in Solid TumorsRhabdomyosarcoma, non-rhabdomyosarcomatous soft tissue sarcoma (including synovial sarcoma, alveolar soft part sarcoma and desmoplastic small round cell tumor), Ewing sarcoma/peripheral Primitive Neuro Ectodermal Tumor (PNET), hepatoblastoma, neuroblastoma (measurable and evaluable), and osteosarcomaMedDRA version: 20.0 Level: HLT Classification code 10019825 Term: Hepatoblastomas System Organ Class: 100000005101MedDRA version: 20.0 Level: PT Classification code 10029260 Term: Neuroblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 15.1 Level: HLGT Classification code 10041299 Term: Soft tissue sarcomas System Organ Class: 100000004864MedDRA version: 20.0 Level: PT Classification code 10031291 Term: Osteosarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: HLT Classification code 10039023 Term: Rhabdomyosarcomas System Organ Class: 100000143528MedDRA version: 20.0 Level: PT Classification code 10015560 Term: Ewing's sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)EUCTR2013-003595-12-SKovartis Pharma Services AG154