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.

Phase I 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 activity of this combination in patients with recurrent hepatocellular carcinoma (HCC) after transplantation. The combination of the mTOR inhibitor, temsirolimus, plus sorafenib has demonstrated safety in a phase I trial in patients with all types of solid tumors, although patients with hepatic dysfunction were not eligible. Because hepatic dysfunction due to underlying cirrhosis exists in at least 80% of patients with advanced HCC, HCC-specific phase I studies of safety, tolerability, and future phase II dosing may be necessary for patients with organ dysfunction.

Phase I is designed to determine the maximum tolerated dose (MTD) and recommended phase II dose for combination temsirolimus and sorafenib in patients with advanced HCC based on the strong preclinical rationale for efficacy in this tumor type, as well as the expectation that toxicity may be greater than in patients with normal hepatic function. Pharmacokinetics of the combination and exploratory biomarker end points will be studied. A phase II study of the combination is planned at the recommended phase II dose upon completion of phase I.

Primary Objective:

  • Determine the MTD and recommended phase II dose

Secondary Objectives:

  • Determine safety/toxicity profile of combination temsirolimus and sorafenib
  • Describe pharmacokinetics of temsirolimus alone in the cohort of 6 patients treated at MTD
  • Describe pharmacokinetics of temsirolimus in combination with sorafenib in the cohort of 6 patients treated at MTD
  • Observe incidence of progression-free survival and disease control rate at 6 months

Contacts: Robin K. Kelley, MD • 415-353-9888 • crss@cc.ucsf.edu

Paula Fiermonte, RN • 415-885-7605 • contacts@cc.ucsf.edu

Daniel Roshevsky • 312-695-1376 • d-roshevsky@northwestern.edu

ClinicalTrials.gov Identifier: NCT01008917

Pralatrexate in Combination with Oxaliplatin in Advanced Esophagogastric Cancer: A Phase II Trial With Predictive Molecular Correlates

Principal Investigator: Nikhil I. Khushalani, MD

Condition: Histologically confirmed carcinoma of the esophagus, stomach, or gastroesophageal junction that is metastatic, or locally advanced and inoperable for cure; histological subtypes permitted included adenocarcinoma, squamous cell carcinoma, or undifferentiated carcinoma (small cell carcinoma variant is not eligible).

Institution: Roswell Park Cancer Institute

Pralatrexate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. Combination pralatrexate and oxaliplatin may kill more tumor cells. This phase II trial is studying how well pralatrexate and oxaliplatin work together in treating patients with unresectable or metastatic esophageal, stomach, or gastroesophageal junction cancer.

Primary Outcome Measure:

  • Overall response rate to combination pralatrexate and oxaliplatin as assessed by RECIST

Secondary Outcome Measures:

  • Toxicity as assessed by NCI CTCAE version 4.0
  • Time to progression
  • Overall survival
  • Whether functionally relevant polymorphisms of genes of the folate metabolism pathway correlate with efficacy and toxicity of pralatrexate
  • Whether response to pralatrexate can be predicted by microRNA expression profiling of the epithelial component of the tumor

Contact: Nikhil I. Khushalani, MD • 716-845-3099 • nikhil.khushalani@roswellpark.org

ClinicalTrials.gov Identifier: NCT01178944

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The goal of the Highlights of the NCCN Oncology Research Program (ORP) is to provide readers with more information on the ORP, including studies currently accruing patients.

For more information on specific trials, including patient selection criteria, please use the contact information listed with each study.

For more information on the NCCN ORP, including a complete detailing of the clinical studies currently underway at NCCN Member Institutions, please access the NCCN ORP pages at http://www.nccn.org/clinical_trials/clinicians.asp.

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