A phase 3 study of XL184 vs mitoxantrone & prednisone in CRPC
- Conditions
- castration-resistant prostate cancer (CRPC)MedDRA version: 17.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-001426-99-GB
- Lead Sponsor
- Exelixis, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 246
1.The subject must have an histological or cytological diagnosis of CRPC (including serum testosterone levels less than 50 ng/dL within 28 days before randomization).
2.The subject must have evidence of bone metastasis related to prostate cancer on bone scans from a protocol credentialed scanner within 28 days before randomization.
3.The subject must have documented pain from bone metastases that requires opioid narcotic intervention. The average daily worst pain intensity reported by the subject during the 7 day Run In Stage, with a minimum of 4 days of reporting, must be at least 4 but no more than 8 on an 11-point NRS.
4.The subject must have adopted a narcotic regimen that consists of one SR opioid agent taken daily for chronic pain (taken on a minimum of 5 days out of the 7 day Run-In Stage) and one IR opioid agent for breakthrough pain, documented during the Run In Stage. The narcotic analgesic regimen must be optimized to provide maximal pain relief without intolerable narcotic-related side effects, according to subject’s goals for comfort and function (see Appendix E).
Note: Subjects requiring narcotic infusions (other than IV push) at screening are not eligible for the study.
5.The subject must have received prior docetaxel and either abiraterone or MDV3100 treatment. For docetaxel: subjects must have received a minimum of three cycles or progressed during or after any amount of a docetaxel containing therapy.
For abiraterone or MDV3100: subjects must have discontinued abiraterone or MDV3100 due to disease progression.
Prostate cancer progression is defined as:
a.PSA progression according to PCWG2 (Prostate Cancer Working Group 2) criteria: PSA level of at least 2 ng/mL which has subsequently risen on at least 2 successive occasions, at least 2 weeks apart. If the second risen value is lower than the first risen value, then an additional test for rising PSA will be required to document progression. The value of the additional test must be higher than the first risen value (Scher et al. 2008).
or
b.Radiographic progression in soft tissue or bone lesions
Note: There is no limit on other prior anticancer treatments, including prior cabazitaxel (except Exclusion Criterion #1).
6.Subjects without prior orchiectomy must be currently taking and willing to continue LHRH analogue (agonist or antagonist) therapy until permanent discontinuation of study treatment.
7.The subject must have recovered to baseline or CTCAE v.4.0 = Grade 1 from toxicities related to any prior treatments, unless AE(s) are clinically non significant or easily manageable (eg, hypertension, hypoalbuminemia, hypophosphatemia).
8.The subject must be = 18 years old on the day of consent.
9.The subject must have adequate organ and marrow function assessed within 7 days before randomization, based on the following:
a.Absolute neutrophil count (ANC) = 1500/mm3
b.Platelets = 100,000/mm3
c.Hemoglobin = 9 g/dL
d.Total bilirubin = 1.5 x the upper limit of normal (for subjects with Gilbert’s disease, = 3 mg/dL)
e.Serum albumin = 2.8 g/dL
f.Serum creatinine = 1.5 x th
1.The subject has received any prior cabozantinib or mitoxantrone.
2.The subject has received docetaxel, abiraterone, or MDV3100 within 2 weeks before randomization.
3.The subject has received any other type of cytotoxic or investigational anticancer agent within 2 weeks before randomization.
4.The subject has received radiation therapy within 4 weeks (includes radiation targeting bone metastases), radionuclide treatment within 6 weeks, or radiation therapy to the thoracic cavity unless radiation targets bone metastases) within 3 months before randomization.
5.The subject has received serotonergic psychiatric medication(s) (Appendix J) within 2 weeks (5 weeks for fluoxetine) before randomization.
6.The subject has known brain metastases or uncontrolled epidural disease.
7.The subject requires at the time of randomization any of the following:
a.Therapeutic doses of anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or FXa (coagulation factor X) inhibitors, antiplatelet agents (eg, clopidogrel), aspirin above low dose levels for cardioprotection per local applicable guidelines, or aspirin in combination with dipyridamole.
Note: Therapeutic doses of heparin are allowed as clinically indicated for supportive treatment after randomization (see Section 7.2).
b.Any additional drugs or herbal products used for the treatment of prostate cancer (including but not limited to chemotherapies other than mitoxantrone, bicalutamide, nilutamide, ketoconazole, diethylstilbestrol [DES], 5 a reductase inhibitors [finasteride, dutasteride], Saw Palmetto, and PC-SPES)
8.The subject has uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
a.Cardiovascular disorders such as symptomatic congestive heart failure, uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment (BP must be controlled at screening), unstable angina pectoris, clinically-significant cardiac arrhythmias, history of stroke (transient ischemic attack or other ischemic event) within 6 months before randomization, myocardial infarction within 6 months before randomization, history of thromboembolic event within 6 months before randomization
b.Gastrointestinal disorders such as malabsorption syndrome, symptomatic cholangitis or gastric outlet obstruction, history of gastric/intestinal perforation, abdominal fistula, or intra-abdominal abscess within 6 months before randomization
c.Other disorders such as active infection requiring systemic treatment; serious non-healing wound/ulcer/bone fracture; organ transplant; uncompensated hypothyroidism
d.History of surgery within 1-6 months before randomization:
i.With wound healing complications – major surgery within 6 months, minor surgery within 3 months;
ii.Without wound healing complications – major surgery within 3 months, minor surgery within 1 month
Note: Complete wound healing from prior surgery is required at least 28 days before randomization.
9.The subject has experienced clinically significant hematemesis or hemoptysis of > 0.5 t
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The objective of this study is to evaluate the safety and efficacy of cabozantinib compared with mitoxantrone plus prednisone.;Secondary Objective: None;Primary end point(s): The primary efficacy endpoint is the proportion of subjects with pain response at Week 6 confirmed at Week 12.;Timepoint(s) of evaluation of this end point: Week 6 and Week 12
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): • Bone scan response at Week 12 per IRF (primary analysis designates subjects with soft tissue progression as non-responders): The stratified CMH test will be used as the primary analysis of this endpoint.<br> • Overall survival: The stratified log-rank test will be used as the primary analysis for this endpoint.<br> ;<br> Timepoint(s) of evaluation of this end point: Bone scan response: Week 12<br> Overall survival: 28 months after the first subject is randomized (expected July 2014).<br>