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.

Several NCCN-sponsored studies funded through the grant mechanism are highlighted below.

Weekly Nanoparticle Albumin-Bound Paclitaxel (Abraxane) Plus Weekly Cetuximab Plus Radiation Therapy in Patients With Stage III to IVB Head and Neck Squamous Cell Carcinoma

Principal Investigator: Matthew Fury, MD, PhD

Condition: Head and neck cancer

Institution: Memorial Sloan-Kettering Cancer Center

Paclitaxel is a standard drug in the management of head and neck cancer, and Abraxane (nanoparticle albumin-bound paclitaxel; Celgene Corporation, Summit, NJ) is a novel formulation of paclitaxel. The purpose of this study is to establish a safe dose range of nanoparticle albumin-bound paclitaxel given in combination with cetuximab and radiation therapy.

All patients will receive standard treatment with definitive radiation therapy (intensity-modulated radiation therapy [IMRT]) plus cetuximab (400 mg/m² intravenous loading dose 1 week prior to radiation therapy, followed by 250 mg/m² weekly intravenous infusions concurrent with radiation therapy). Weekly nanoparticle albumin-bound paclitaxel will also be given intravenously concurrently with radiation therapy, according to the dose escalation scheme.

The total number of planned cetuximab infusions is 8 (loading dose + 7 weekly infusions concurrent with radiation therapy). The total number of planned nanoparticle albumin-bound paclitaxel infusions is 7 (all concurrent with radiotherapy). Up to 5 dose levels of weekly nanoparticle albumin-bound paclitaxel will be explored.

Primary Outcome Measures:

• Establish the phase II recommended dose of weekly intravenous albumin-bound paclitaxel (Abraxane) given concurrently with weekly cetuximab plus definitive radiation therapy (IMRT) for patients with head and neck squamous cell carcinoma (HNSCC)

Secondary Outcome Measures:

• Establish the safety and tolerability of weekly albumin-bound paclitaxel plus cetuximab plus radiation therapy for patients with HNSCC

Contact: Matthew Fury, MD, PhD • 212-639-3049

ClinicalTrials.gov Identifier: NCT00736619

Phase I Trial of Hepatic Arterial Infusion of Abraxane With a Pharmacokinetic Study in Advanced Solid Cancer Patients With Predominant Hepatic Metastases

Principal Investigator: Razelle Kurzrock, MD, BS

Conditions: Liver cancer, advanced cancers, solid tumors

Institution: The University of Texas MD Anderson Cancer Center

Abraxane is designed to block cancer cells from dividing, which may cause the cells to die. Administering Abraxane directly into the liver may allow a higher dose of the drug to be given, while avoiding some of the side effects that occur when high doses of chemotherapy are given other ways (e.g., intravenously into an arm).

Primary Objectives:

• Determine the maximum tolerated dose of hepatic arterial infusion (HAI) of Abraxane in advanced solid cancer patients with predominant hepatic metastases

• Compare pharmacokinetic analyses of HAI Abraxane and intravenous Abraxane, especially the time to peak that might be a more sensitive indicator of the effect of first-pass hepatic extraction on drug bioavailability

Secondary Objectives:

• Assess by RECIST clinical response signals in a broad array of solid tumors

• Evaluate whether dynamic contrast-enhanced MRI, to determine the degree of vascular permeability, and PET scan, to delineate tumor viability and glucose uptake, are able to predict major clinical outcomes

Contacts: Vivianne Velez-Bravo • 713-563-2561

Razelle Kurzrock, MD • 713-794-1226

ClinicalTrials.gov Identifier: NCT00732836

A Phase II Trial of Alemtuzumab-Ofatumumab Combination in Previously Untreated Symptomatic Chronic Lymphocytic Leukemia

Principal Investigator: Shuo Ma, MD, PhD

Condition: Chronic lymphocytic leukemia

Institution: Robert H. Lurie Comprehensive Cancer Center of Northwestern University

This multicenter phase II trial studies the efficacy and toxicity of combination alemtuzumab and ofatumumab as front-line therapy for patients with chronic lymphocytic leukemia (CLL). Alemtuzumab and ofatumumab are monoclonal antibodies approved as a single agent for the treatment of CLL. Eligible patients must have a confirmed diagnosis of CLL and symptomatic disease requiring therapy. A total of 60 patients will be enrolled in the study, with 30 at the United States site (Northwestern University) and 30 at the Sweden site (Karolinska University Hospital). Patients receive alemtuzumab subcutaneously 3 times a week in weeks 1 to 18, and ofatumumab intravenously on day 1 of weeks 3, 5, 7, 9, 11, 13, 15, and 17. The responses will be assessed after treatment completion per the iwCLL2008 guideline. Patients will be followed up for up to 5 years or until initiation of second-line therapy, whichever comes first. The accompanying NCCN-funded correlative studies are to determine the clinical and pathological factors impacting clinical response to the alemtuzumab-ofatumumab combination immunotherapy.

Objective:

• Determine the efficacy and safety of combination alemtuzumab and ofatumumab in previously untreated CLL

Primary End Point:

• Response rates (including complete remission, partial remission, stable disease, progressive disease, and minimal residual disease assessment) as defined by the iwCLL2008 criteria

Secondary End Points:

• Progression-free survival, therapy-free survival, and overall survival

• Treatment toxicity

• Correlation of pretreatment clinical and biologic characteristics with clinical outcomes

• Efficacy as compared with results from the historical control of the NU 04H6 alemtuzumab-rituximab study

Correlative End Points:

• Determine the clinical and pathological factors impacting clinical response to the alemtuzumab-ofatumumab combination immunotherapy. Treatment response will be compared between subsets of patients with various clinical features, as determined by results of clinical studies including Rai staging, cytogenetics by FISH, IgVH mutation status, and ZAP70. Additionally, the research correlative studies will include complement activity, membrane bound complement regulatory proteins, and FCγR2a and FCγR3a polymorphisms will be studied and correlated with the treatment response.

• Characterize the immunological changes occurring during alemtuzumab-ofatumumab combination therapy. This will include monitoring the B, T, NK cell counts, serum immunoglobulin levels, viral serology titers, and viral load throughout the course of treatment.

Contacts: Shuo Ma, MD, PhD • 312-908-5250 • shuo-ma@northwestern.edu

Study Coordinator • 312-695-1301 • cancertrials@northwestern.edu

ClinicalTrials.gov Identifier: NCT01361711