Format

Send to

Choose Destination
Clin Cancer Res. 2015 Aug 1;21(15):3420-7. doi: 10.1158/1078-0432.CCR-14-3370. Epub 2015 Mar 18.

A Phase I/II Trial of BNC105P with Everolimus in Metastatic Renal Cell Carcinoma.

Author information

1
City of Hope Medical Center, Duarte, California. spal@coh.org.
2
BC Cancer Agency, Vancouver, British Columbia, Canada.
3
University of Washington, Seattle, Washington.
4
Medical University of South Carolina, Charleston, South Carolina.
5
Mayo Clinic, Rochester, Minnesota.
6
University of Texas Health Science Center, San Antonio, Texas.
7
National Cancer Center, Singapore.
8
University of New Mexico Cancer Center, Albuquerque, New Mexico.
9
Indiana University Health Goshen Center for Cancer Care, Goshen, Indiana.
10
Nebraska Cancer Specialists/Nebraska Methodist Hospital, Omaha, Nebraska.
11
Dana-Farber Cancer Center, Boston, Massachusetts.
12
Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
13
University of Alabama, Birmingham, Alabama.
14
Texas Oncology, Fort Worth, Texas.
15
Hoosier Cancer Research Network, Indianapolis, Indiana.
16
Bionomics, Thebarton, South Australia, Australia.
17
Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas.

Abstract

PURPOSE:

BNC105P inhibits tubulin polymerization, and preclinical studies suggest possible synergy with everolimus. In this phase I/II study, efficacy and safety of the combination were explored in patients with metastatic renal cell carcinoma (mRCC).

EXPERIMENTAL DESIGN:

A phase I study in patients with clear cell mRCC and any prior number of therapies was conducted using a classical 3 + 3 design to evaluate standard doses of everolimus with increasing doses of BNC105P. At the recommended phase II dose (RP2D), patients with clear cell mRCC and one to two prior therapies (including ≥ 1 VEGF-TKI) were randomized to BNC105P with everolimus (arm A) or everolimus alone (arm B). The primary endpoint of the study was 6-month progression-free survival (6MPFS). Secondary endpoints included response rate, PFS, overall survival, and exploratory biomarker analyses.

RESULTS:

In the phase I study (N = 15), a dose of BNC105P at 16 mg/m(2) with everolimus at 10 mg daily was identified as the RP2D. In the phase II study, 139 patients were randomized, with 69 and 67 evaluable patients in arms A and B, respectively. 6MPFS was similar in the treatment arms (arm A: 33.82% vs. arm B: 30.30%, P = 0.66) and no difference in median PFS was observed (arm A: 4.7 mos vs. arm B: 4.1 mos; P = 0.49). Changes in matrix metalloproteinase-9, stem cell factor, sex hormone-binding globulin, and serum amyloid A protein were associated with clinical outcome with BNC105P.

CONCLUSIONS:

Although the primary endpoint was not met in an unselected population, correlative studies suggest several biomarkers that warrant further prospective evaluation.

PMID:
25788492
PMCID:
PMC4526387
DOI:
10.1158/1078-0432.CCR-14-3370
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center