Oncology Research Program

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.

NCCN studies funded through the grant mechanism are highlighted below.

Phase II Trial of the Combination of Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma

Principal Investigators: Robin K. Kelley, MD, and Halla Nimeiri, MD

Condition: Advanced hepatocellular carcinoma

Institutions: University of California, San Francisco and Robert H. Lurie Comprehensive Cancer Center of Northwestern University

The combination of sorafenib with an inhibitor of the mammalian target of rapamycin (mTOR) pathway demonstrates additive and possibly synergistic antitumor effects in preclinical models, and there is anecdotal evidence for anticancer activity when mTOR inhibitors for immunosuppression are combined with sorafenib in patients with recurrent hepatocellular carcinoma (HCC) after liver transplant.

This phase II trial is being conducted after completion of a phase I study of the combination of temsirolimus and sorafenib in first-line therapy of 25 patients with advanced HCC (December 2009–April 2012). The maximum tolerated dose and recommended phase II dose of the combination was intravenous temsirolimus, 10 mg weekly plus oral sorafenib, 200 mg twice daily.

Primary Objective:

• Determine the median time to progression (TTP) in patients with advanced HCC treated with combination temsirolimus and sorafenib

Secondary Objectives:

• Determine response rate (RR) using RECIST 1

• Measure median progression-free survival (PFS)

• Measure median overall survival (OS)

• Measure time to treatment failure (TTF)

• Measure change in α-fetoprotein (AFP) tumor marker and examine for association between change in AFP and TTP and best response

• Characterize toxicity and tolerability of combination temsirolimus and sorafenib, including describing frequency of dose reductions, delays, and discontinuation for toxicity

Exploratory Objectives and Other Assessments:

• Describe TTP, RR, PFS, OS, TTF, and AFP response; toxicity; and tolerability in subsets defined by hepatitis B virus (HBV), hepatitis C virus, Asian, and non-Asian status

• Compare degree of association between median TTP and OS with response by RECIST version 1.1 and modified RECIST after 2 cycles of protocol therapy

• Enumerate circulating tumor cells at baseline and after 1 and 2 cycles of therapy to evaluate for any relationship between baseline levels and change in levels with median TTP and/or OS

• In patients with chronic active HBV infection or exposure, monitor hepatitis viral load during and after therapy with an mTOR inhibitor

• Bank peripheral blood specimens and leftover archival pathology or cytology specimens for future research

• Characterize baseline mTOR pathway activation by immunohistochemistry (IHC) for selected markers, such as pS6RP, pAKT, PTEN, and LKB1, and by tumor next-generation DNA sequencing of targeted genes, including the mTOR pathway, in archival tumor specimens from patients with HCC treated with temsirolimus plus sorafenib

• Examine the relationship between baseline mTOR pathway activation by IHC and sequencing, and clinical outcomes on treatment with temsirolimus plus sorafenib

Contacts:

University of California, San Francisco

Robin K. Kelley, MD • 415-353-9888 • katie.kelley@ucsf.edu

Jennifer Luan • 415-514-6220 • Jennifer.Luan@ucsf.edu

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Erin Alonso, CCRC • 312-695-4168 • erinalonso@northwestern.edu

ClinicalTrials.gov Identifier: NCT01687673