Open Label Phase II Trial of Cabozantinib in Patients With Metastatic Castrate Resistant Prostate Cancer (mCRPC) and Known Amplifications or Activating Mutations in Gene Targets of Cabozantinib or Liver Metastases Who Have Received Prior Anti-Androgen Therapy
概览
- 阶段
- 2 期
- 干预措施
- Cabozantinib
- 疾病 / 适应症
- Prostate Cancer
- 发起方
- Weill Medical College of Cornell University
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- Median radiographic progression-free survival (rPFS) using Kaplan-Meier methodology
- 状态
- 终止
- 最后更新
- 昨天
概览
简要总结
The purpose of this study is to determine what effects (good and bad) cabozantinib has in treatment of patients with metastatic castrate resistant prostate cancer (mCRPC).
The hypothesis for this trial is that cabozantinib has anti-tumor activity in a molecularly-selected group of patients with CRPC or patients with liver metastases.
详细描述
This is a single-arm, open-label Phase II multi-institutional trial in 30 patients who have been molecularly selected based on that their tumors possess alterations in molecular targets of cabozantinib or who have liver metastases. Patients will be treated be continuously until they develop radiographic progression or discontinue cabozantinib for toxicity. If 6 or more out of 12 subjects with particular mutation or gene amplification show progression prior to 6 months, accrual for the particular genomic alteration may close. In addition, a series of correlative studies will be performed including tissue biopsies in order to further define the mechanisms of cabozantinib anti-tumor action in prostate cancer and identify surrogate markers of response. This research study is being done because additional effective treatments are needed for prostate cancer that has spread and is growing despite hormone suppression. Prior studies indicate that Cabozantinib may be effective in a subset of these participants, but that has not yet been determined. About 30 subjects will take part in this study across all participating sites. We expect to enroll approximately 20 participants at Weill Cornell Medicine and approximately 3-5 subjects per participating site. All subjects participating in this study will be treated with Cabozantinib. All subjects will continue to take LHRH analogue therapy. Once eligible participants will be enrolled on the trial for approximately approximately 12 months. At that point, subjects will switch to long-term follow up for two years after removal from the study or until death, whichever occurs first. Study related procedures can be combined with routine Standard of Care (SOC) visits. These will include obtaining medical history, vitals, routine blood collection, radiographic imaging (CT, MRI and Bone scan), EKG and between 2 and 4 weeks after starting therapy, a tumor biopsy is required. This will be done with a needle by local sedation by an Interventional Radiologist.
研究者
入排标准
入选标准
- •Age \>18 years.
- •Documented histological or cytological diagnosis of prostate carcinoma.
- •Evidence of metastatic PC on imaging (bone scan and/or CT/MRI scan)
- •\- Patients with liver metastases must have biopsy proven evidence of metastatic prostate cancer in the liver.
- •Agree to undergo a biopsy of at least one metastatic site or primary prostate prior to beginning therapy. Adequate archival metastatic tissue can be used if available in lieu of a biopsy if done when patient had CRPC and within 6 months of the start of treatment.
- •Agree to undergo a biopsy of at least one metastatic site or primary prostate after 3 weeks of therapy (biopsy must be between day 21 and day 24 of treatment). Re-biopsy of same pre-treatment biopsy soft tissue site especially liver metastases is preferred.
- •Serum testosterone level less than 50 ng/dl. Subjects without prior orchiectomy must be currently taking and willing to continue luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) therapy until permanent discontinuation of study treatment.
- •Documented progressive metastatic CRPC based on at least one of the following criteria:
- •PSA progression according to Prostate Cancer Working Group 3 (PCWG3) criteria
- •Objective radiographic progression, according to PCWG3 criteria
排除标准
- •Prior treatment with cabozantinib
- •Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
- •Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) except agents to maintain castrate status within 4 weeks before first dose of study treatment. Antiresportive bone agents are also allowed.
- •Subject has received abiraterone acetate or enzalutamide within 2 weeks before enrollment.
- •Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
- •Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment for neurological indications at the time of first dose of study treatment.
- •Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
- •Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
- •Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
- •The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 14 days before the first dose of study treatment.
研究组 & 干预措施
Cabozantinib Arm
干预措施: Cabozantinib
结局指标
主要结局
Median radiographic progression-free survival (rPFS) using Kaplan-Meier methodology
时间窗: From initiation of treatment to minimum of radiographic progression, approximately 6 months.
Radiographic progression will be assessed based on PCWG-modified RECIST criteria for soft-tissue lesions and bone lesions. Radiographic progress-free survival (rPFS) is defined as time from start of treatment to minimum of radiographic progression.
Median Radiographic Progression-free Survival (rPFS) Using Kaplan-Meier Methodology
时间窗: From initiation of treatment to minimum of radiographic progression, approximately 6 months.
Radiographic progression will be assessed based on PCWG-modified RECIST 1.1 criteria for soft-tissue lesions and protocol-specific criteria for bone lesions. Progressive disease (PD) for soft-tissue lesions is defined as an increase ≥ 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started, or the appearance of one or more new lesions, or the appearance of new lesions. Progressive disease (PD) criteria for bone lesions is assessing whether there are either "no new lesions" or "new lesions", which will be confirmed on a second scan performed 6 or more weeks later. Radiographic progress-free survival (rPFS) is defined as time from start of treatment to minimum of radiographic progression.
次要结局
- Change in prostate specific antigen (PSA)(From initiation of treatment to minimum of radiographic progression, at approximately 6 months after start of treatment.)
- Overall survival (OS)(Patients will be followed every 12 weeks up to 2 years after completion of study)
- Proportion of patients with a tumor response(From initiation of treatment to minimum of radiographic progression, at approximately 6 months after start of treatment.)
- Number of adverse events(From initiation of treatment to 30 days after last dose of treatment)
- Change in Prostate Specific Antigen (PSA)(From initiation of treatment to minimum of radiographic progression, at approximately 6 months after start of treatment.)
- Overall Survival (OS)(Patients will be followed every 12 weeks up to 2 years after completion of study)
- Number of Patients With a Tumor Response(From initiation of treatment to minimum of radiographic progression, at approximately 6 months after start of treatment.)
- Number of Adverse Events(From the time of signing consent through their End of Treatment visit, which is 30 days after the date of the last dose of cabozantinib treatment, approximately 12 months.)