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NIH Research Portfolio Online Reporting Tools (Report) Report, Data and Analyses of NIH Research Activities
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ARRA Investments in the ACTNOW Cancer Program

Public Health Burden
Cancer is the second leading cause of death in the United States after heart disease. In 2009, it is estimated that nearly 1.5 million new cases of invasive cancer will be diagnosed in this country and more than 560,000 people will die of the disease.

ACTNOW (Accelerating Clinical Trials of Novel Oncologic Pathways) is an early-phase clinical trial program designed to help shorten the time it takes to move new cancer treatments from the discovery phase, to drug development, and, ultimately, to approval and safe use by cancer patients. The trials funded under ACTNOW are phase I, phase I/II, or phase II studies of agents that target and disrupt molecular pathways that cancer cells use to grow, metastasize, and become resistant to current treatments. ARRA funding is providing support to 37 ACTNOW clinical trials. Tested agents include the following:
  • ABT-888: This drug blocks the activity of proteins called PARP1 and PARP2, which help repair damaged DNA in cells. Cells unable to repair extensive DNA damage cannot survive. In most of the trials, chemotherapy drugs that damage DNA are being given in combination with ABT-888. The rationale is that ABT-888 will interfere with the repair of DNA damage caused by the drugs, and the resulting higher levels of damaged DNA in cancer cells will cause them to die. ABT-888 is also being tested alone in cancer patients who have DNA repair deficiencies due to mutations in other DNA repair proteins, such as BRCA1 and BRCA2. In these patients, ABT-888 might accelerate the pace in which cancer cells accumulate lethal levels of DNA damage.1,2,3,4,5
  • GDC-04495: This agent is an inhibitor of a cell signaling pathway known as Hedgehog, which is thought to play a role in cell proliferation, survival, and differentiation. Hedgehog signaling appears to be inactive in most adult tissues; however, it becomes reactivated in several types of cancer.6,7,8,9,10,11,12
  • AZD2171 (cediranib): This drug  inhibits the function of proteins called vascular endothelial growth factor receptors, which play a role in the growth of new blood vessels to tumors. Tumors cannot grow larger than a few millimeters in diameter unless they obtain an adequate blood supply to provide the oxygen and nutrients they need for continued growth.13,14,15
  • AZD6244: This drug inhibits the activity of proteins called MEK1 and MEK2, which are components of a cell signaling pathway that regulates cell proliferation and survival. This signaling pathway often functions abnormally in cancer cells.16,17,18
  • IMC-A12 (HuMab IGF-1R): This agent is a human monoclonal antibody directed against a protein called the type-1 insulin-like growth factor receptor (IGF-1R). Signaling pathways  activated by IGF-1R play a role in regulating cell proliferation and survival, and overexpression of this protein has been shown in several types of human cancer.19,20,21,22
  • NTX-010 (Seneca Valley Virus-001): NTX-010 is an oncolytic virus, which means it selectively kills tumor cells. This naturally occurring virus has not been shown to cause disease in humans, but it has been shown to target and kill human tumor cells that have neuroendocrine properties. In preliminary research, NTX-010 has demonstrated activity against a variety of adult and childhood cancers. 23
  • Alvocidib (flavopiridol): Alvocidib inhibits cell proliferation by blocking the activity of proteins called cyclin-dependent kinases. It has shown activity against solid tumors and hematologic (blood system) cancers. 24

  1. 3U01CA099168-07S2 -- A phase I study of ABT-888 in combination with carboplatin and paclitaxel in advanced solid malignancies -- Egorin, Merrill J. (PA)
  2. 3U01CA099168-07S2 -- A phase I study of chronically-dosed, single-agent ABT-888 in patients with either BRCA 1/2-mutated cancer; platinum-refractory ovarian, fallopian tube, or primary peritoneal cancer; or basal-like breast cancer -- Egorin, Merrill J. (PA)
  3. 3U01CA081457-11S4 -- A phase I study of ABT-888, an oral inhibitor of poly(ADP-ribose) polymerase and temozolomide in children with recurrent/refractory CNS tumors -- Boyett, James M. (TN) (Pediatric Brain Tumor Consortium)
  4. 3U10CA027469-29S2 -- A phase I study of carboplatin/paclitaxel/bevacizumab and ABT-888 in newly diagnosed patients with previously untreated epithelial ovarian, fallopian tube, or primary peritoneal cancer -- DiSaia, Philip J. (MD) (Gynecologic Oncology Group)
  5. N01CM062207-8-0-2 -- ABT-888 as monotherapy and in combination with mitomycin C in patients with solid tumors with deficiency in homologous recombination repair -- Villalona-Calero, Miguel A. (OH)
  6. 3U01CA137443-01S1 -- Phase II study of GDC-0449 (NSC 747691) in patients with recurrent glioblastoma multiforme -- Grossman, Stuart A. (MD) (Adult Brain Tumor Consortium)
  7. 3U01CA062487-16S1 -- A phase I/II dose-escalation and exploratory neoadjuvant study of an oral gamma-secretase inhibitor (GSI), plus Hedgehog inhibitor GDC-0449 (NSC #747691) administered in patients with breast cancer -- LoRusso, Patricia M. (MI)
  8. 3U10CA021115-35S1 -- A randomized phase II study of cisplatin and etoposide in combination with either Hedgehog inhibitor GDC-0449 or IGF-1R MOAB IMC-A12 for patients with extensive stage small cell lung cancer -- Comis, Robert L. (PA) (Eastern Cooperative Oncology Group)
  9. 3U01CA081457-11S4 -- A phase I pharmacokinetic and safety study in children with recurrent or refractory medulloblastoma to identify a pharmacokinetic-based dose for GDC-0449 -- Boyett, James M. (TN) (Pediatric Brain Tumor Consortium)
  10. 3U01CA081457-11S4 -- A phase II clinical trial evaluating the efficacy and safety of GDC-0449 in adults with recurrent or refractory medulloblastoma -- Boyett, James M. (TN) (Pediatric Brain Tumor Consortium)
  11. N01CM62204-8-0-2 -- A randomized, phase II study of FOLFOX in combination with bevacizumab plus or minus GDC-0449 in patients with advanced gastric adenocarcinoma -- Sparano, Joseph (NY)
  12. N01CM62201-9-0-2 -- A phase IB/randomized phase II trial of gemcitabine plus GDC-0449, a Hh pathway inhibitor, in patients with metastatic pancreatic cancer -- Vokes, Everett E (IL)
  13. 3U01CA062490-16S1 -- A phase I study of AZD2171 and WBRT in patients with brain metastases from non-small cell lung cancer -- Kufe, Donald W. (MA)
  14. 3U01CA137443-01S1 -- Cediranib and cilengitide for recurrent glioblastoma -- Grossman, Stuart A. (MD) (Adult Brain Tumor Consortium)
  15. 3U01CA062490-16S1 -- Phase I/II study of AZD2171 and AZD2281 in combination for treatment of recurrent platinum-sensitive papillary-serous ovarian, fallopian tube or peritoneal cancer or for treatment of recurrent triple-negative breast cancer -- Kufe Donald W. (MA)
  16. 3U01CA070095-15S1 -- A phase I open label, dose-escalation trial evaluating the safety and tolerability of AZD6244 and IMC-A12 in subjects with advanced solid malignancies -- Carducci, Michael A. (MD)
  17. 3U01CA062490-16S1 -- Phase II clinical trial of the MEK 1/2 inhibitor AZD6244 in cancers with BRAF mutations identified by prospective genotypic analysis -- Kufe, Donald W. (MA)
  18. N01CM62206-8-0-2 -- Phase II trial of AZD6244 in melanoma patients harboring mutations in BRAF -- Kelsen, David P. (NY)
  19. 3U01CA069856-15S1 -- Phase I/II trial of anti-IGF-IR monoclonal antibody IMC-A12 plus MTOR inhibitor CCI-779 in chemo-naive, castrate metastatic prostate cancer -- Spriggs, David (NY)
  20. 3U01CA097452-07S1 -- A phase I study of IMC-A12 (anti-insulin-like growth factor-I receptor monoclonal antibody) in combination with CCI-779 (temsirolimus) in pediatric patients with recurrent or refractory solid tumors -- Blaney, Susan M. (CA) (Childhood Oncology Group Phase I Consortium)
  21. 3U10CA021115-35S1 -- Three-arm randomized phase II study of carboplatin and paclitaxel in combination with cetuximab, IMC-A12, or both for advanced non-small cell lung cancer patients who are not candidates for bevacizumab-based therapy -- Comis, Robert L. (PA) (Eastern cooperative Oncology Group)
  22. N01CM62206-8-0-2 -- A phase II study of temsirolimus (CC-779, NSC-683864) and IGF-1 receptor antibody IMC-A12 (NSC-742460) in patients with metastatic sarcomas -- Kelsen, David P. (NY)
  23. 3U01CA097452-07S1 -- A phase I dose escalation study of Seneca Valley Virus (SVV-001), a replication-competent picorna virus, in relapsed/refractory pediatric patients with neuroblastoma, rhabdomyosarcoma, Ewing family of tumors, and rare tumors with neuroendocrine features -- Blaney, Susan M. (Childhood Oncology Group Phase I Consortium)
  24. N01CM62206-8-0-2 -- A non-randomized phase II study of alvocidib (flavopiridol) plus oxaliplatin with or without 5-FU and leucovorin for relapsed or refractory germ-cell tumors -- Kelsen, David P. (NY)

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