Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Many patients with stage III pancreatic cancer have tumors that are technically unresectable because of local vessel impingement or invasion by tumor. These patients may benefit from palliation of biliary obstruction by endoscopic, surgical, or radiological means.[1]

Although some data demonstrate a survival advantage associated with combined chemotherapy and radiation therapy,[2][Level of evidence: 1iiA] most patients with unresectable pancreatic cancer should be considered for participation in clinical trials. Radiation therapy alone may palliate symptoms, but a survival benefit is not demonstrable. Chemotherapy alone occasionally produces an objective antitumor response, but the limited survival warrants participation in clinical trials. Gemcitabine has shown durable disease palliation in patients with advanced or metastatic pancreatic cancer refractory to fluorouracil (5-FU).[3] A phase III trial of gemcitabine versus 5-FU as first-line therapy in patients with advanced or metastatic adenocarcinoma of the pancreas reported a significant improvement in survival among patients treated with gemcitabine (1-year survival was 18% with gemcitabine as compared with 2% with 5-FU, P = .003).[4][Level of evidence: 1iiA] A preliminary report, in abstract form, of a phase III trial in which 569 patients with advanced or metastatic pancreatic carcinomas showed that erlotinib (100 mg/day) modestly prolonged survival when combined with gemcitabine (1,000 mg/m² weekly) compared with gemcitabine alone.[5,6] Differences in overall survival favored the erlotinib arm (hazard ratio = 0.81; 95% confidence interval, 0.67–0.97; P = .025). The corresponding median and 1-year survival rates for patients receiving erlotinib versus placebo were 6.4 months and 5.9 months, and 24% versus 17%, respectively.[5][Level of evidence: 1iiA]

Pain associated with unresectable pancreatic cancer may be palliated with radiation therapy, with or without chemotherapy,[2,7-9] or with chemical splanchnicectomy with 50% alcohol at the time of surgical exploration.[10] Celiac nerve blocks and local neurosurgical procedures to relieve pain can be considered.[11]

Standard treatment options:

1. Pancreatectomy when feasible, with or without adjuvant 5-FU chemotherapy and radiation therapy.[10,12-15]



2. Radiation therapy with 5-FU chemotherapy for patients with locally unresectable disease.[2,7,8]



3. Palliative surgical biliary and/or gastric bypass, percutaneous radiologic biliary stent placement, or endoscopic biliary stent placement.[16,17]

Treatment options under clinical evaluation:

1. For patients with resected tumors, postoperative radiation therapy with other chemotherapeutic agents. In 2002, the Radiation Therapy Oncology Group completed a prospective, multicenter randomized trial to evaluate whether gemcitabine chemotherapy administered prior to and following radiation with concurrent 5-FU is superior to adjuvant 5-FU for patients with completely resected tumors; preliminary analysis is pending.[18]



2. For patients with resected tumors, postoperative chemotherapy alone. The European Study for Pancreatic Cancer-3 trial is ongoing to evaluate postoperative chemotherapy with either 5-FU/leucovorin or gemcitabine versus no additional treatment.[19]



3. For patients with technically unresectable tumors, biologic agents in combination with radiation and/or chemotherapy [20]



4. For patients with locally unresectable tumors, radiation combined with novel chemotherapeutic agents and/or radiosensitizers.[21] Gemcitabine is being explored in combination with radiation therapy.[22]



5. Intraoperative radiation therapy and/or implantation of radioactive sources.[9,23]

Information about ongoing clinical trials is available from the NCI Web site.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III pancreatic cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Sohn TA, Lillemoe KD, Cameron JL, et al.: Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J Am Coll Surg 188 (6): 658-66; discussion 666-9, 1999.  [PUBMED Abstract]
   
   
2. Moertel CG, Frytak S, Hahn RG, et al.: Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer 48 (8): 1705-10, 1981.  [PUBMED Abstract]
   
   
3. Rothenberg ML, Moore MJ, Cripps MC, et al.: A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol 7 (4): 347-53, 1996.  [PUBMED Abstract]
   
   
4. Burris HA 3rd, Moore MJ, Andersen J, et al.: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15 (6): 2403-13, 1997.  [PUBMED Abstract]
   
   
5. Moore MJ, Goldstein D, Hamm J, et al.: Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group [NCIC-CTG]. [Abstract] J Clin Oncol 23 (Suppl 16): A-1, 1s, 2005. 
   
   
6. Moore MJ, NCIC-Clinical Trials Group: Phase III Randomized Study of Gemcitabine With or Without Erlotinib in Patients With Unresectable Locally Advanced or Metastatic Pancreatic Cancer, CAN-NCIC-PA3, Clinical trial, Closed.  [PDQ Clinical Trial]
   
   
7. Whittington R, Solin L, Mohiuddin M, et al.: Multimodality therapy of localized unresectable pancreatic adenocarcinoma. Cancer 54 (9): 1991-8, 1984.  [PUBMED Abstract]
   
   
8. Moertel CG, Childs DS Jr, Reitemeier RJ, et al.: Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet 2 (7626): 865-7, 1969.  [PUBMED Abstract]
   
   
9. Tepper JE, Noyes D, Krall JM, et al.: Intraoperative radiation therapy of pancreatic carcinoma: a report of RTOG-8505. Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 21 (5): 1145-9, 1991.  [PUBMED Abstract]
   
   
10. Kalser MH, Ellenberg SS: Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120 (8): 899-903, 1985.  [PUBMED Abstract]
    
    
11. Polati E, Finco G, Gottin L, et al.: Prospective randomized double-blind trial of neurolytic coeliac plexus block in patients with pancreatic cancer. Br J Surg 85 (2): 199-201, 1998.  [PUBMED Abstract]
    
    
12. Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer 59 (12): 2006-10, 1987.  [PUBMED Abstract]
    
    
13. Klinkenbijl JH, Jeekel J, Sahmoud T, et al.: Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg 230 (6): 776-82; discussion 782-4, 1999.  [PUBMED Abstract]
    
    
14. Neoptolemos JP, Dunn JA, Stocken DD, et al.: Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 358 (9293): 1576-85, 2001.  [PUBMED Abstract]
    
    
15. Neoptolemos JP, Stocken DD, Friess H, et al.: A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350 (12): 1200-10, 2004.  [PUBMED Abstract]
    
    
16. van den Bosch RP, van der Schelling GP, Klinkenbijl JH, et al.: Guidelines for the application of surgery and endoprostheses in the palliation of obstructive jaundice in advanced cancer of the pancreas. Ann Surg 219 (1): 18-24, 1994.  [PUBMED Abstract]
    
    
17. Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.  [PUBMED Abstract]
    
    
18. Regine WF, Radiation Therapy Oncology Group: Phase III Randomized Study of Adjuvant Fluorouracil-Based Chemoradiotherapy Preceded and Followed By Fluorouracil Versus Gemcitabine in Patients With Resected Adenocarcinoma of the Pancreas, RTOG-9704, Clinical trial, Closed.  [PDQ Clinical Trial]
    
    
19. ESPAC-3(v2) Phase III Adjuvant Trial in Pancreatic Cancer Comparing 5FU and D-L-Folinic Acid vs. Gemcitabine. Leeds, UK: National Cancer Research Network Trials Portfolio, 2004. Available online. Last accessed August 28, 2007. 
    
    
20. Rich TA, Radiation Therapy Oncology Group: Phase II Randomized Study of Gemcitabine, Paclitaxel, and Radiotherapy With or Without Tipifarnib in Patients With Locally Advanced Pancreatic Cancer, RTOG-PA-0020, Clinical trial, Closed.  [PDQ Clinical Trial]
    
    
21. Epelbaum R, Rosenblatt E, Nasrallah S, et al.: Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer. J Surg Oncol 81 (3): 138-43, 2002.  [PUBMED Abstract]
    
    
22. Li CP, Chao Y, Chi KH, et al.: Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: gemcitabine versus 5-fluorouracil, a randomized controlled study. Int J Radiat Oncol Biol Phys 57 (1): 98-104, 2003.  [PUBMED Abstract]
    
    
23. Reni M, Panucci MG, Ferreri AJ, et al.: Effect on local control and survival of electron beam intraoperative irradiation for resectable pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys 50 (3): 651-8, 2001.  [PUBMED Abstract]
    
    

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