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.

A Multi-Institution Phase II Study of Pralatrexate With Vitamin B12 and Folic Acid Supplementation for Previously Treated Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC)

Principal Investigator: Alan Ho, MD, PhD

Condition: Head and neck cancer

Institution: Memorial Sloan-Kettering Cancer Center, New York, New York

The purpose of this study is to determine if the experimental drug pralatrexate, with the vitamins folic acid and vitamin B12, is an effective treatment for head and neck cancer in patients previously treated with chemotherapy. Methotrexate has been used for a long time to treat head and neck cancer patients, and pralatrexate was designed to be a new drug that works better. Laboratory studies have shown that pralatrexate works better than methotrexate at killing cancer cells.

Pralatrexate has already been studied in patients with other types of cancers, such as lymphoma and lung cancer. The results from those studies were promising. Pralatrexate was recently approved by the FDA as a new treatment for peripheral T-cell lymphoma.

Primary Outcome Measure: To determine the overall response rate (CR+PR)

Secondary Outcome Measures:

• To determine the best overall response rate at the end of treatment with pralatrexate

• To estimate median progression-free survival (PFS)

• To estimate median overall survival (OS)

• To quantify the mRNA transcript levels of reduced folate carrier (RFC-1) in study patients and correlate to best overall response with pralatrexate

• To evaluate the impact of pralatrexate on circulating endothelial cells (CECs) and circulating progenitor cells (CPCs) and correlate to best overall response with pralatrexate

Contact: Alan Ho, MD, PhD • 212-639-3311

ClinicalTrials.gov Identifier: NCT01183065

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

Conditions: Liver cancer; advanced cancers; solid tumors (currently only recruiting cervical cancer patients)

Institution: The University of Texas MD Anderson Cancer Center, Houston, Texas

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

Primary Objectives:

• Determine the maximum tolerated doses 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 responses 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

Title: A Phase I Study of Bendamustine and Bevacizumab for Patients With Advanced Cancers

Principal Investigator: Apostolia M. Tsimberidou, MD, PhD

Condition: Advanced cancers

Institution: The University of Texas MD Anderson Cancer Center, Houston, Texas

Bendamustine is designed to damage the DNA of cancer cells. Bendamustine also interferes with the creation of new DNA, which may keep cancer cells from repairing themselves or forming new cancer cells. Bevacizumab is designed to block the growth of blood vessels that supply the nutrients needed for tumor growth, which may prevent or slow down the growth of cancer cells.

Patients will be assigned to a dose level of bendamustine based on when they join the study. Up to 4 dose levels of bendamustine will be tested. Three participants (to a maximum of 6) will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, provided no intolerable side effects were seen. This will continue until the highest tolerable dose of bendamustine is found. All participants will receive the same dose level of bevacizumab.

Objectives:

• Determine the maximum tolerated dose (MTD), dose limiting toxicities (DLT), and tolerability of bendamustine and bevacizumab in patients with advanced cancers.

• Assess the antitumor efficacy of this combination regimen.

Contact: Apostolia M. Tsimberidou, MD, PhD

Study Coordinator: Adoneca Fortier • pager: 713-606-5564

ClinicalTrials.gov Identifier: NCT01152203