Highlights of the NCCN Oncology Research Program

The NCCN Oncology Research Program (ORP) strives to improve the quality of life for patients and reduce cancer-related deaths by advancing cancer therapies through research. Since the program's establishment in 1999, the NCCN ORP has brought millions of dollars in research grants to investigators at NCCN Member Institutions. Research grants are provided to NCCN through collaborations with pharmaceutical and biotechnology companies; these grants are in turn used to support scientifically meritorious cancer research efforts.

NCCN ORP studies typically explore new avenues of clinical investigation and seek answers to important cancer-related questions. All studies are approved and funded through a scientific peer-review process and are overseen by the ORP.

An NCCN study funded through the grant mechanism are highlighted below.

A Phase I/II Study of Nintedanib and Capecitabine in Refractory Metastatic Colorectal Cancer

Principal Investigator: Patrick Boland, MD

Condition: Metastatic colorectal cancer

Institution: Roswell Park Cancer Institute and City of Hope Comprehensive Cancer Center

This study is an open-label, nonrandomized, multicenter, phase I/II study of nintedanib and capecitabine in patients with metastatic colorectal cancer refractory to irinotecan- and oxaliplatin-based therapy. The study will include an abbreviated phase I dose-finding portion, followed by a nonrandomized phase II component. Nintedanib and capecitabine are both oral formulations, to be taken twice daily.

Nintedanib will be administered at a fixed dose and the total daily dose of capecitabine will be administered at standard doses of 2000 mg/m² daily split into 2 comparable portions. For the purposes of this study, a cycle will be defined as 3 weeks (ie, 21 days). Nintedanib is to be self-administered twice daily for 21 days (ie, 1 complete cycle), whereas capecitabine will be dosed cyclically, in a 2 weeks on/1 week off fashion.

Disease assessment will occur after every 3 cycles of therapy (9 weeks). For the phase I study, patients will be evaluated for toxicity on days 1 and 8 of the first 2 cycles. Otherwise, all patients will be evaluated on day 1 of each cycle of therapy. Treatment will continue until disease progression, in the absence of undue toxicity.

Primary Objectives:

Phase I:

• Estimate the maximum tolerated dose and examine the dose-limiting toxicities of nintedanib when administered with capecitabine in order to establish the recommended phase II dose

Phase II:

• Assess progression-free survival at 18 weeks via the RECIST version 1.1 guidelines after every 3 cycles (9 weeks) of therapy

Secondary Objectives (Phase II):

• Assess median progression-free survival via RECIST version 1.1 guidelines

• Assess median overall survival from the date of enrollment to the time of death

• Assess the objective response rate as measured by RECIST v 1.1

• Assess the toxicity of dose regimen using the CTEP NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

Tertiary Objectives:

• Measure circulating angiogenic cytokines: vascular endothelial growth factor (VEGF), soluble VEGF receptors 1/2, placental growth factor, granulocyte-macrophase colony-stimulating factor, leptin, IL-1a, IL-8, IL-6, basic fibroblast growth factor, osteopontin, and pentraxin 3

• Measure drug levels and PK/PD modeling

Contacts:

Roswell Park Cancer Institute • 877-275-7724 • ASKRPCI@roswellpark.org

City of Hope: Marwan Fakih, MD • 626-256-4673 ext 63087 • mfakih@coh.org

ClinicalTrials.gov Identifier: NCT02393755