ARRA IMPACT REPORT:
Accelerating Clinical Trials of Novel Oncologic PathWays (ACTNOW)


Public Health Burden
Cancer is the second leading cause of death in the United States after heart disease. In 2012, it is estimated that nearly 1.6 million new cases of invasive cancer will be diagnosed in this country, and more than 577,000 Americans will die of cancer.

ACTNOW Overview
For a novel cancer therapy to become standard treatment for patients, it must first go through several clinical trial phases. The early phases (I-II) test the safety of the treatment and look for evidence that it is effective. If a therapy is safe and effective, it will proceed to testing in a phase III trial, which compares the new therapy with the current standard of care.

Accelerating Clinical Trials of Novel Oncologic PathWays (ACTNOW) is a National Cancer Institute (NCI) phase I-II clinical trials program that has the potential to accelerate the rate at which new cancer therapies move from the discovery phase to clinical usage. More specifically, the goal is for trials to begin enrolling patients or be under review by local institutional review boards within 90 days of receiving funding, about nine months faster than NCI’s current protocol to test the clinical utility of new cancer therapies. ACTNOW aims to increase the number of targeted drug therapies being used in the clinic. A quicker delivery of novel targeted cancer therapies to patients could potentially result in more lives saved from the disease.

How ARRA Funding Is Supporting ACTNOW
ARRA funding provided NCI researchers the necessary resources to develop, approve, and conduct clinical trials of molecularly targeted cancer therapies within an expedited timeframe. ACTNOW received $36 million in ARRA funds, which was used to hire staff, acquire innovative technologies for diagnostic scans, complete specimen sample collection and assay development, and reimburse research costs for data management at local trial sites. Funding also was used to monitor trial enrollment to ensure trial completion within two years.

ACTNOW Progress
ACTNOW is supporting 37 phase I, phase I/II, and phase II cancer therapy trials that test novel agents that target the pathways by which cancer cells grow, metastasize, or develop resistance to current standard therapies. Several of these trials have already made progress:

  • The University of Pittsburgh Cancer Institute used ACTNOW funding to hire four additional researchers, enabling it to accelerate two studies of a promising new drug, ABT-888, for women with inoperable breast or ovarian cancer. ABT-888 blocks the activity of BRCA proteins called PARP1 and PARP2, which help to repair DNA damage in cells caused by chemotherapy. Cells that are unable to repair extensive DNA damage ultimately die. The BRCA proteins are also involved in DNA repair, so tumors with BRCA gene mutations are anticipated to be particularly susceptible to PARP inhibitors such as ABT-888. A phase I study of ABT-888 in combination with chemotherapy treatment found that the treatment was well tolerated and had promising activity in a subset of patients with BRCA gene mutations. A phase II trial of the therapy is ongoing in patients with BRCA mutation-positive ovarian cancer, triple-negative breast cancer, and low-grade lymphoma.1
  • The Children’s Oncology Group conducted a phase I/II study of cixutumumab (IMC-A12) in children with refractory solid tumors. IMC-A12 is a human monoclonal antibody against a protein called type-1 insulin-like growth factor receptor (IGF-1R). Signaling pathways activated by IGF-1R are involved in regulating cell growth and survival; overexpression of this protein has been discovered in several types of cancer. The phase I/II study showed that IMC-A12 was well tolerated in children and identified a recommended phase II dose for the agent.2
  • The University of Texas MD Anderson Cancer Center conducted a study of IMC-A12 in combination with temsirolimus in patients with refractory Ewing sarcoma family tumors. Temsirolimus is a kinase inhibitor that works by blocking the action of an abnormal protein that stimulates cancer cell growth and proliferation. The study showed that IMC-A12 combined with temsirolimus was well-tolerated and provided preliminary evidence of durable antitumor activity in heavily pretreated Ewing sarcoma family tumors.3
  • The Gynecologic Oncology Group conducted a phase II study of bevacizumab in patients with recurrent or persistent endometrial cancer. Bevacizumab is a human monoclonal antibody against vascular endothelial growth factor-A. Vascular endothelial growth factors play a role in the growth of new blood vessels to tumors. Tumors are unable to grow larger than a few millimeters in diameter unless they are supplied with an adequate amount of blood to provide the oxygen and nutrients needed for continued growth. The phase II study showed that the agent was well-tolerated and active in patients with endometrial cancer (based on the number of patients whose disease had progressed within six months of receiving treatment) and warrants further investigation in this disease.4
  • The Dana-Farber Cancer Institute is currently conducting a phase Ib/II trial of cediranib (AZD2171), chemotherapy (temozolomide), and radiation combinatorial therapy in newly diagnosed glioblastoma patients. Cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for the growth of new blood vessels to the tumor. Giving cediranib to patients in combination with chemotherapy and radiation therapy may kill more gliobastoma tumor cells.5

Contributing NIH Institutes & Centers

  • National Cancer Institute (NCI)

  1. 3U01CA099168-07S2, http://www.ncbi.nlm.nih.gov/pubmed/22307137 - CHU, EDWARD - UNIVERSITY OF PITTSBURGH AT PITTSBURGH - PITTSBURGH - PA
  2. 3U01CA097452-07S1, http://www.ncbi.nlm.nih.gov/pubmed/22184397 - BLANEY, SUSAN M - NATIONAL CHILDHOOD CANCER FOUNDATION - ARCADIA - CA
  3. 3U01CA062487-16S1, http://www.ncbi.nlm.nih.gov/pubmed/22465830 - LORUSSO, PATRICIA MUCCI - WAYNE STATE UNIVERSITY - DETROIT - MI
  4. 3U10CA027469-29S2, http://www.ncbi.nlm.nih.gov/pubmed/21537039 - DISAIA, PHILIP J - GYNECOLOGIC ONCOLOGY GROUP - CROFTON - MD
  5. 3U01CA062490-16S3 - KUFE, DONALD W. - DANA-FARBER CANCER INSTITUTE - BOSTON - MA