A Randomized Discontinuation Study of XL184 in Subjects With Advanced Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Exelixis
- 入组人数
- 730
- 试验地点
- 37
- 主要终点
- Bone Scan Response (BSR) - NRE, CRPC
研究概览
简要总结
This is a Phase 2 study to evaluate the efficacy and safety of cabozantinib (XL184) in subjects with selected advanced tumor types.
详细描述
The goal of this clinical trial was to learn about the efficacy, safety, and tolerability of cabozantinib against a placebo in subjects with Metastatic Breast Cancer (MBC), Gastric and Gastroesophageal Junction Cancer (GEJ), Hepatocellular Carcinoma (HCC), Melanoma, Non-small Cell Lung Cancer (NSCLC), Ovarian (primary peritoneal or fallopian tube carcinoma), Pancreatic Cancer, Castration-Resistant Prostate Cancer (CRPC), or Small cell Lung Cancer (SCLC) with advanced tumors.
The main questions this study aimed to answer were:
- What is the efficacy of cabozantinib in subjects with advanced solid tumors?
- What is the safety and efficacy of cabozantinib at two starting dose levels 100 milligrams (mg) once daily (po QD) and 39.4 mg po QD? Please note: that the 39.4 mg, po QD was only used in the Non-Randomized Expansion (NRE) part of the study
There were three stages to the Randomized Discontinuation Trial (RDT):
- The Lead in Stage: This stage enrolled eligible patients with advanced solid tumors who received open-label cabozantinib at 100 mg once daily for 12 weeks.
- The Randomized Stage: Subjects who demonstrated stable disease (SD) at the end of 12 weeks of the Lead-in Stage were randomized to receive cabozantinib or placebo (a look-alike substance that contains no active drug) in a blinded manner.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •The subject has a cytologically or histologically and radiologically confirmed, advanced, recurrent, or metastatic solid tumor of the nine types listed below:
- •Pancreatic Cancer
- •Castration-Resistant Prostate Cancer (CRPC)
- •Hepatocellular Carcinoma (HCC)
- •Gastric or Gastroesophageal Junction Cancer
- •Small Cell Lung Cancer (SCLC)
- •Ovarian cancer, primary peritoneal or fallopian tube carcinoma
- •Breast cancer that is one of the following subtypes: estrogen receptor positive breast cancer, estrogen receptor/progesterone receptor/HER2-negative (triple-negative), or inflammatory (regardless of receptor status) disease histology
- •Non-Small Cell Lung Cancer (NSCLC)
- •Certain requirements for prior therapies may apply
- •The subject has documented progressive disease at screening
- •Subjects having any tumor type of other than CRPC must have at least one lesion that is not within a previously irradiated field and is measurable on CT or MRI scan
- •The subject has recovered to baseline or CTCAE ≤ Grade 1 from toxicities related to prior treatment (some exceptions apply)
- •The subject is ≥ 18 years old on the day of consent
- •Tissue samples from archival or fresh tissue, or a tissue block of the subject's tumor
- •The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •The subject has adequate organ function
- •The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document
- •Sexually active fertile subjects (male and female), and their partners, must agree to use medically accepted methods of contraception during the course of the study and for 3 months after the last dose of the study drug(s)
- •Female subjects of childbearing potential must have a negative pregnancy test at screening
排除标准
- •The subject has experienced clinically-significant hematemesis or hemoptysis of >0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
- •The subject has a cavitating pulmonary lesion(s) or a pulmonary lesion abutting or encasing a major blood vessel
- •Certain restrictions on prior treatments apply
- •The subject has known symptomatic or uncontrolled brain metastases or epidural disease
- •The subject has prothrombin time/International Normalized Ratio (PT/INR) or partial thromboplastin time (PTT) test results that are above (1.3x)the laboratory upper limit of normal
- •The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or Coumadin-related agents, heparin, thrombin or FXa inhibitors, and antiplatelet agents (low-dose aspirin (≤81 mg/day), low-dose warfarin (≤1mg/day, and prophylactic low molecular weight heparin (LMWH) are permitted)
- •The subject has a corrected QT interval(QTcF)>500 ms at screening
- •The subject has uncontrolled, significant intercurrent illness
- •The subject is unable to swallow capsules
- •The subject is pregnant or breastfeeding
- •The subject has a previously-identified allergy or hypersensitivity to components of the study treatment formulation
- •The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
- •The subject has had another diagnosis of malignancy requiring systemic treatment within the last two years, unless non-melanoma skin cancer, in-situ carcinoma of the cervix, or superficial bladder cancer
研究组 & 干预措施
Lead-in Stage - cabozantinib (XL184)
Open Label, cabozantinib, 100 mg, po QD for 12 weeks.
干预措施: Cabozantinib (Drug)
Randomized Stage - cabozantinib (XL184)
Blinded, cabozantinib, 100 mg, po QD until disease progression.
干预措施: Cabozantinib (Drug)
Randomized Stage - placebo
Blinded, placebo, 100 mg, po QD until disease progression.
干预措施: Placebo (Drug)
Open-Label Extension - cabozantinib (XL184)
Open Label, cabozantinib, for subjects that were on placebo during the randomized stage, 100 mg, po QD until disease progression or unacceptable toxicity.
干预措施: Cabozantinib (Drug)
Non-Randomized Expansion (NRE) Cohort - Castrate Resistant Prostate Cancer (CRPC), 100mg
Open Label, cabozantinib, 100 mg, po QD until disease progression or unacceptable toxicity.
干预措施: Cabozantinib (Drug)
Non-Randomized Expansion (NRE) Cohort - Castrate Resistant Prostate Cancer (CRPC), 39.4mg
Open Label, cabozantinib, 39.4, po QD until disease progression or unacceptable toxicity.
干预措施: Cabozantinib (Drug)
A. Non-Randomized Expansion (NRE) Cohort - Ovarian
Open Label, cabozantinib, 100 mg, po QD until disease progression or unacceptable toxicity.
干预措施: Cabozantinib (Drug)
结局指标
主要结局
Bone Scan Response (BSR) - NRE, CRPC
时间窗: From initial dose through final study visit up to 15 months
The reduction of bone scan lesion area (BSLA) by \> 30% was used as the quantitative measure of BSR. BSR was a primary outcome measure for only the NRE CRPC Cohorts.
Progression-Free Survival (PFS) - Randomized Stage, RDT Cohorts Only
时间窗: From initial dose through final study visit up to 44 months
Progression Free Survival during the Randomized Stage (Randomized Population)
Objective Response Rate (ORR) - LEAD IN STAGE, RDT Cohorts and NRE Ovarian Cohort Only
时间窗: From initial dose through final study visit up to 44 months
Objective response rate (ORR) per modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.0 per investigator The analysis of ORR in the RDT Cohorts were defined as the proportion of subjects with a best overall response of confirmed complete response (CR) or partial response (PR) per mRECIST 1.0 during the 12-week Lead-In Stage. In the NRE Ovarian Cohort, mRECIST 1.1 was used. ORR for the NRE CRPC Cohorts was not a primary objective and is therefore not captured in the table below.
次要结局
- Duration of Objective Response (OR) - Responders From Lead-in Stage(From initial dose through final study visit up to 44 months)
- Progression Free Survival (PFS) - Throughout the Study(From initial dose through final study visit up to 44 months)
- Duration of Bone Scan Response - NRE Cohorts, CRPC Only(From initial dose through final study visit up to 15 months)
- Overall Survival (OS) - NRE Cohorts, CRPC and Ovarian Only(From initial dose through final study visit up to 15 months)