Phase III Trial of Enzalutamide (NSC# 766085) Versus Enzalutamide, Abiraterone and Prednisone for Castration Resistant Metastatic Prostate Cancer
Patients are randomized to one of two treatment groups: enzalutamide or enzalutamide,
abiraterone and prednisone. Treatment will continue until disease progression or
unacceptable toxicity. Patients are followed for clinical outcomes for a maximum of 5 years
post study treatment. The primary and secondary objectives are described below.
1. Primary Objective:
To compare the overall survival of patients with progressive metastatic
castration-resistant prostate cancer (CRPC) treated with either enzalutamide only or
enzalutamide with abiraterone and prednisone
2. Secondary Objectives:
- To assess the grade 3 or higher toxicity profile and compare safety by treatment
arm.
- To assess and compare post-treatment prostate-specific antigen (PSA) declines by
treatment arm.
- To compare radiographic progression free survival defined by Prostate Cancer
Working Group 2 (PCWG2), and objective response rate, by treatment arm.
- To test for radiographic progression free survival (rPFS) treatment interaction in
predicting overall survival.
- To assess pre- and post-treatment measures of tumor burden and bone activity using
sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT)
and technetium (Tc) methylene diphosphonate (MDP) bone scintigraphy and correlate
these measures with overall survival.
- To develop and validate prognostic and predictive models of overall survival that
include baseline clinical and molecular markers.
A Phase II Randomized Study Comparing Two Doses of Carfilzomib (NSC-756640) With Dexamethasone for Multiple Myeloma Patients With Relapsed or Refractory Disease
PRIMARY OBJECTIVES:
I. To evaluate and compare progression free survival (PFS) of two different doses of
carfilzomib with dexamethasone in multiple myeloma (MM) patients with relapsed and/or
refractory disease.
SECONDARY OBJECTIVES:
I. To evaluate and compare response rates (RR) for each arm. II. To evaluate response rates
(RR) for patients that relapse on low dose carfilzomib and subsequently cross-over to high
dose carfilzomib.
III. To evaluate the safety of this combination for this patient population. IV. To evaluate
overall survival (OS).
TERTIARY OBJECTIVES:
I. To explore the molecular variability in MM cells obtained from extramedullary bone marrow
relapse sites.
II. To explore the role of positron emission tomography (PET) scanning in assessing disease
burden and as a tool to assess treatment response.
III. To explore changes in left ventricular ejection fraction (LVEF) in patients with
relapsed or refractory multiple myeloma treated with low dose carfilzomib or high dose
carfilzomib plus dexamethasone.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive dexamethasone intravenously (IV) and low-dose carfilzomib IV over
2-10 minutes on days 1, 2, 8, 9, 15, and 16. Patients with progression cross-over to Arm II.
ARM II: Patients receive dexamethasone IV and high-dose carfilzomib IV over 30 minutes on
days 1, 2, 8, 9, 15, and 16.
Note that for the first course of treatment on both arms carfilzomib is given at a reduced
rate to assess toxicity.
In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 3 years
from initial registration.
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