A Phase 3, Randomized, Double-blind, Controlled Study of Cabozantinib (XL184) vs. Prednisone in Metastatic Castration-resistant Prostate Cancer Patients who have Received Prior Docetaxel and Prior Abiraterone or MDV3100

Phase 3

Recruiting

• Conditions: bone metastases; Prostate cancer; 10038597; 10036958

• Registration Number: NL-OMON37289
• Lead Sponsor: PPD

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 40

Inclusion Criteria

1. Documented histological or cytological diagnosis of prostate cancer.
2. Serum testosterone levels less than 50 ng/dL within 28 days before randomization.
3. Evidence of bone metastasis related to prostate cancer on bone scans from a protocol-credentialed scanner using technetium-99m labeled methylene diphosphonate (Tc99-MDP) radiotracer within 28 days before randomization. ;Note: Tc99-MDP is the preferred tracer. In situations where this tracer is unavailable, other tracers such as Tc99 dicarboxypropane diphosphonate (Tc99-DPD), Tc99 hydroxymethylene diphosphonate (Tc99-HDP), or Tc99-hidroximetilenodifosfonato (Tc99-HMDP) may be used. At the discretion of the Sponsor other Tc99 bone-seeking radiopharmaceuticals not designated above may be allowed.
4. The subject must have received prior docetaxel (minimum cumulative dose of 225 mg/m2) and either abiraterone or MDV3100 treatment and have evidence of investigator-assessed prostate cancer progression on each agent independently.
For docetaxel: subjects must have progressed during or after 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 anti-cancer treatments, including prior cabazitaxel (except Exclusion Criterion #1).
5. 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.
6. Subject must have recovered to baseline or CTCAE v.4.0 (Common Terminology Criteria for Adverse Events, version 4.0) <= Grade 1 from toxicities related to any prior treatments, unless AE(s) are clinically non significant and/or stable on supportive therapy.
7. >= 18 years old on the day of consent.
8. ECOG performance status: 0-2
9. Adequate organ and marrow function, defined as follows, based upon laboratory tests performed within 7 days before randomization:
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 >= 3 g/dL
f. Serum creatinine <= 1.5 x the upper limit of normal or calculated creatinine clearance >= 50 mL/min or GFR > 30 mL/min.
Note: For GFR estimation, the Cockcroft and Gault equation should be used [GFR = CrCl (mL/min) = (140 - age) x wt (kg)/(serum creatinine x 72)]
g. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 x the upper limit of normal
h. Lipase < 1.5 times the upper limit of normal
i. Serum phosphorus >= lower limit of normal
j. Urine protein/creatinine ratio (UPCR) <= 1
10. The subject must be capable of understanding and complying with the protocol re

Exclusion Criteria

1. The subject has received prior cabozantinib.
2. The subject has received docetaxel, abiraterone, or MDV3100 within 2 weeks before randomization.
3. The subject has received any other type of anti-cancer agent (except agents to maintain castrate status) within 2 weeks before randomization.
4. The subject has received radiation therapy within 4 weeks (includes radiation targeting bone metastases) or radionuclide treatment within 6 weeks of randomization. Subject is excluded if there is any prior history of radiation therapy to the mediastinum (unless radiation targeted bone metastases).
5. Radiographic evidence of metastasis to the liver.
6. The subject has known brain metastases or cranial epidural disease
7. The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or FXa inhibitors, or antiplatelet agents (eg, clopidogrel). Low dose aspirin (<= 81 mg/day), low-dose warfarin (<= 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted.
8. The subject requires chronic concomitant treatment of strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John*s Wort).
9. Uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
a. Cardiovascular disorders such as symptomatic congestive heart failure (CHF), uncontrolled hypertension defined as sustained 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 (including TIA, 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 or gastric outlet obstruction.
c. Risks for GI perforation or fistula formation which include intra-abdominal tumor/metastases invading GI tract; active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, diverticulitis, cholecystitis or symptomatic cholangitis or appendicitis; history of abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess, or prior GI surgery (particularly when associated with delayed or incomplete healing) within 6 months before first dose of study treatment. Complete healing following abdominal surgery or resolution of intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib.
d. Risk for non-GI fistula formation which includes previous surgical intervention (such as PEG tube placement) and evidence of intraluminal disease involving the trachea or esophagus.
e. Other disorders such as active infection requiring systemic treatment; serious non-healing wound/ulcer/bone fracture; organ transplant; uncompensated hypothyroidism, uncontrolled diabetes mellitus
f. History of surgery within 6 months before randomization:
• With wound healing complications - major surgery within 6 months, minor surgery within 3 months;
• 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 30 days before randomization.
10. Clinica

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary efficacy endpoint:<br /><br>Overall survival</p><br>