We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov Menu

Oxaliplatin, Capecitabine and Avastin for Metastatic Esophagogastric Adenocarcinoma (XAGastric)

This study has been completed.
ClinicalTrials.gov Identifier:
First Posted: March 14, 2007
Last Update Posted: February 13, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Hoffmann-La Roche
Genentech, Inc.
Information provided by (Responsible Party):
Duke University
The purpose of this study is to evaluate the progression free survival of capecitabine (Xeloda), oxaliplatin and bevacizumab (Avastin) in previously untreated metastatic esophagogastric adenocarcinomas.

Condition Intervention Phase
Esophageal Neoplasms Stomach Neoplasms Neoplasm Metastasis Drug: capecitabine (Xeloda), oxaliplatin and bevacizumab (Avastin) Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase ll Study of Oxaliplatin, Capecitabine, and Bevacizumab in the Treatment of Metastatic Esophagogastric Adenocarcinomas

Resource links provided by NLM:

Further study details as provided by Duke University:

Primary Outcome Measures:
  • Median Progression-Free Survival (PFS) [ Time Frame: 5 years from study start date ]
    Time in months from the start of study treatment to the date of first progression (PD) according to the RECIST criteria, or death due to any cause. PER RECIST, a PD is indicated when there is at least a 20% increase in the sum of the longest diameters from target lesions relative to the smallest sum recorded since treatment is initiated. Median PFS was estimated using a Kaplan-Meier curve, and is the time at which 50% of patients remain alive without disease progression.

Secondary Outcome Measures:
  • To Assess the Safety and Tolerability of the Combination of Bevacizumab, Oxaliplatin and Capecitabine in Patients With Previously Untreated Metastatic Esophagogastric Adenocarcinoma [ Time Frame: Every 21 days ]
    Number of subjects who experienced an adverse event

  • Response Rate [ Time Frame: Every 9 weeks for up to 1 year ]
    The proportion of patients for whom the best overall response is complete response (CR) or partial response (PR). A CR occurs when all lesions disappear; whereas, a PR is indicated when there is at least a 30% decrease in the sum of the longest diameters (LD) of the target lesion. A PD (progressive disese) occurs when there is at least a 20% increase in the sum of the LD relative to the smallest sum LD recorded since treatment is initiated. Disease is considered stable if there is no response and no PD. All patients were assigned a best response for inclusion in this calculation in accordance with the protocol.

  • Median Survival [ Time Frame: 5 years after study start date ]
    Time in months from the start of study treatment to date of death due to any cause. Median survival was estimated using a Kaplan-Meier curve and is the time point at which 50% of patients remain alive.

Enrollment: 60
Study Start Date: February 2007
Study Completion Date: July 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: capecitabine (Xeloda), oxaliplatin and bevacizumab (Avastin)

Capecitabine will be administered orally at a twice daily dose of 850 mg/m2 (equivalent to a total daily dose of 1700 mg/m2) given days 1-14 of the three week cycle.

Oxaliplatin will be administered at the dose of 130 mg/m2 given as a 2-hour intravenous infusion on day 1 of a three week cycle.

Bevacizumab will be administered at a dose of 15 mg/kg given as a 30-90 minute intravenous infusion on day 1 of a three week cycle following the administration of oxaliplatin.

Detailed Description:

The number of new cases of esophageal and gastric cancers in the United States in 2005 is 14520 for esophageal cancer and 21860 for gastric cancer. Unfortunately, esophageal and gastric cancers will also account for 13570 and 11550 deaths, respectively, in 2005. The 5 year survival rates for metastatic gastroesophageal, GE junctional, and gastric cancers are less than 5%. The major current treatment modality for patients with advanced esophageal, GE junctional, and gastric adenocarcinomas is systemic chemotherapy.

We seek to investigate the efficacy of capecitabine and oxaliplatin in combination with bevacizumab as first line treatment for metastatic esophagogastric cancers. The choice of capecitabine and oxaliplatin is made to develop a user-friendly biologically-based regimen, offering patients oral capecitabine in place of continuous 5FU infusion pumps. Since capecitabine can be given crushed this regimen may both be active and user-friendly. Preliminary data in colorectal cancer suggest that the regimen of capecitabine, oxaliplatin, and bevacizumab has comparable activity to FOLFOX-bevacizumab. The goal of the proposed regimen is to define a capecitabine and oxaliplatin-based regimen that optimizes biological approaches over cytotoxic approaches. The addition of bevacizumab to chemotherapy regimens for metastatic colorectal cancer, metastatic non-small cell lung cancer, and metastatic breast cancer has shown to improve response rates and overall survival. If active, this regimen could serve as a first line comparator to the capecitabine, oxaliplatin, and epirubicin combination. This approach will also help to simplify regimen development across gastrointestinal cancers.

In addition to the primary efficacy endpoint of this protocol, several correlative endpoints will also be examined in an exploratory manner. The importance of developing blood-based and tumor biomarkers has been extensively reviewed. However, the role of such predictive markers has not been well studied for XELOX-A. This information is important since it may help define which populations are most likely to benefit and most likely to suffer significant toxicity from this important GI cancer regimen. This biomarker approach may also help understand and define mechanisms of sensitivity, resistance, and toxicity that may be used to guide future hypothesis-driven studies designed to improve the efficacy and safety of this regimen. The correlative biomarker endpoints include serum, plasma and urine biomarkers (e.g. VEGF and bFGF), a wound healing model of angiogenesis, and tumor biopsy studies .


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Primary Inclusion Criteria:

  • Histologically or cytologically documented and radiographically measurable adenocarcinoma of the esophagus or stomach that is metastatic/recurrent and not amenable to potentially curative treatment
  • No prior therapy for metastatic disease
  • Prior radiation therapy is permitted, provided it is completed > 28 days prior to day 1 of study drug
  • Normal organ and marrow function
  • Karnofsky Performance Status 70-100%

Primary Exclusion Criteria:

  • Unstable or poorly controlled hypertension > 150/100 mm Hg
  • Arterial thromboembolic events within 6 months
  • Clinically significant uncontrolled cardiac disease
  • Significant proteinuria at baseline
  • Grade 2 or greater peripheral neuropathy
  • History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00447330

United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
University of Wake Forest Baptist Medical Center
Winston Salem, North Carolina, United States, 27157-0001
Sponsors and Collaborators
Duke University
Hoffmann-La Roche
Genentech, Inc.
Principal Investigator: Hope E Uronis, MD Duke University
  More Information

Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin. 2005 Jan-Feb;55(1):10-30. Erratum in: CA Cancer J Clin. 2005 Jul-Aug;55(4):259.
Bollschweiler E, Wolfgarten E, Gutschow C, Hölscher AH. Demographic variations in the rising incidence of esophageal adenocarcinoma in white males. Cancer. 2001 Aug 1;92(3):549-55.
Wijnhoven BP, Siersema PD, Hop WC, van Dekken H, Tilanus HW. Adenocarcinomas of the distal oesophagus and gastric cardia are one clinical entity. Rotterdam Oesophageal Tumour Study Group. Br J Surg. 1999 Apr;86(4):529-35.
Glimelius B, Ekström K, Hoffman K, Graf W, Sjödén PO, Haglund U, Svensson C, Enander LK, Linné T, Sellström H, Heuman R. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol. 1997 Feb;8(2):163-8.
Hsu CH, Yeh KH, Chen LT, Liu JM, Jan CM, Lin JT, Chen YC, Cheng AL. Weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin in the treatment of advanced gastric cancers. An effective and low-toxic regimen for patients with poor general condition. Oncology. 1997 Jul-Aug;54(4):275-80.
Leichman L, McDonald B, Dindogru A, Samson M, Vaitkevicius VK. Cisplatin. An active drug in the treatment of disseminated gastric cancer. Cancer. 1984 Jan 1;53(1):18-22.
Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O'Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol. 1997 Jan;15(1):261-7.
Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, Shimma N, Umeda I, Ishitsuka H. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer. 1998 Jul;34(8):1274-81.
Schüller J, Cassidy J, Dumont E, Roos B, Durston S, Banken L, Utoh M, Mori K, Weidekamm E, Reigner B. Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol. 2000;45(4):291-7.
Hong YS, Song SY, Lee SI, Chung HC, Choi SH, Noh SH, Park JN, Han JY, Kang JH, Lee KS, Cho JY. A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol. 2004 Sep;15(9):1344-7.
Koizumi W, Saigenji K, Ujiie S, Terashima M, Sakata Y, Taguchi T; Clinical Study Group of Capecitabine. A pilot phase II study of capecitabine in advanced or recurrent gastric cancer. Oncology. 2003;64(3):232-6.
Kim TW, Kang YK, Ahn JH, Chang HM, Yook JH, Oh ST, Kim BS, Lee JS. Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced gastric cancer. Ann Oncol. 2002 Dec;13(12):1893-8.
Evans TR, Pentheroudakis G, Paul J, McInnes A, Blackie R, Raby N, Morrison R, Fullarton GM, Soukop M, McDonald AC. A phase I and pharmacokinetic study of capecitabine in combination with epirubicin and cisplatin in patients with inoperable oesophago-gastric adenocarcinoma. Ann Oncol. 2002 Sep;13(9):1469-78.
Al-Batran SE, Atmaca A, Hegewisch-Becker S, Jaeger D, Hahnfeld S, Rummel MJ, Seipelt G, Rost A, Orth J, Knuth A, Jaeger E. Phase II trial of biweekly infusional fluorouracil, folinic acid, and oxaliplatin in patients with advanced gastric cancer. J Clin Oncol. 2004 Feb 15;22(4):658-63.
Louvet C, André T, Tigaud JM, Gamelin E, Douillard JY, Brunet R, François E, Jacob JH, Levoir D, Taamma A, Rougier P, Cvitkovic E, de Gramont A. Phase II study of oxaliplatin, fluorouracil, and folinic acid in locally advanced or metastatic gastric cancer patients. J Clin Oncol. 2002 Dec 1;20(23):4543-8.
Díaz-Rubio E, Evans TR, Tabemero J, Cassidy J, Sastre J, Eatock M, Bisset D, Regueiro P, Baselga J. Capecitabine (Xeloda) in combination with oxaliplatin: a phase I, dose-escalation study in patients with advanced or metastatic solid tumors. Ann Oncol. 2002 Apr;13(4):558-65.
Cassidy J, Tabernero J, Twelves C, Brunet R, Butts C, Conroy T, Debraud F, Figer A, Grossmann J, Sawada N, Schöffski P, Sobrero A, Van Cutsem E, Díaz-Rubio E. XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol. 2004 Jun 1;22(11):2084-91.
Shields AF, Zalupski MM, Marshall JL, Meropol NJ. Treatment of advanced colorectal carcinoma with oxaliplatin and capecitabine: a phase II trial. Cancer. 2004 Feb 1;100(3):531-7.
de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000 Aug;18(16):2938-47.
Sumpter K, Harper-Wynne C, Cunningham D, Rao S, Tebbutt N, Norman AR, Ward C, Iveson T, Nicolson M, Hickish T, Hill M, Oates J. Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF. Br J Cancer. 2005 Jun 6;92(11):1976-83.
Chong G, Cunningham D. Can cisplatin and infused 5-fluorouracil be replaced by oxaliplatin and capecitabine in the treatment of advanced oesophagogastric cancer? The REAL 2 trial. Clin Oncol (R Coll Radiol). 2005 Apr;17(2):79-80.
Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004 Jun 3;350(23):2335-42.
Giantonio, B., et al. High-dose bevacizumab in combination with FOLFOX4 improves survival in patients with previously treated advanced colorectal cancer: Results from the Eastern Cooperative Oncology Group (ECOG) study E3200. in Proc Am Soc Clin Oncol. 2005.
Miller, K.D., et al. E2100: A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first line threapy for locally recurrent or metastatic breast cancer. in American Society for Clinical Oncology. 2005. Orlando, FL.
Shah, M.A., et al. A Multicenter Phase II Study of Irinotecan (CPT), Cisplatin (CIS), and Bevacizumab (BEV) in Patients with Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma. in Proc Am Soc Clin Oncol. 2005.
Goldberg, R.M., et al. N9741: oxaliplatin (Oxal) or CPT-11 + 5-fluorouracil (5FU)/leucovorin (LV) or oxal + CPT-11 in advanced colorectal cancer (CRC). Updated efficacy and quality of life (QOL) data from an intergroup study. in Proc Am Soc Clin Oncol. 2003.
Takimoto CH, Remick SC, Sharma S, Mani S, Ramanathan RK, Doroshow J, Hamilton A, Mulkerin D, Graham M, Lockwood GF, Ivy P, Egorin M, Schuler B, Greenslade D, Goetz A, Knight R, Thomas R, Monahan BP, Dahut W, Grem JL; National Cancer Institute Organ Dysfunction Working Group Study. Dose-escalating and pharmacological study of oxaliplatin in adult cancer patients with impaired renal function: a National Cancer Institute Organ Dysfunction Working Group Study. J Clin Oncol. 2003 Jul 15;21(14):2664-72.
Xeloda Investigator Drug Brochure (Ro 09-1978), in Version 6. January 2002.
Ishitsuka, H., T. Ishikawa, and Y. Fukase. Capecitabine and the dThdPase up-regulators IFN-gamma or taxol showed synergistic activity in human cancer xenografts. in Proc Am Assoc Cancer Res. 1996.
Giantonio, B.J., et al. Incorporating angiogenesis inhibition with bevacizumab (anti-VEGF) into frontline chemotherapy with irinotecan (CPT-11), fluorouracil and leucovorin (FU/LV) for advanced colorectal cancer (advCRC): a toxicity analysis of ECOG study E2200. in Proc Am Soc Clin Oncol. 2002.
Hochster, H., et al. Bevacizumab (B) with oxaliplatin (O)-based chemotherapy in the first-line therapy of metastatic colorectal cancer (mCRC): Preliminary results of the randomized モTREE-2ヤ trial. in Proc Am Soc Clin Oncol. 2005.
Poon RT, Fan ST, Wong J. Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol. 2001 Feb 15;19(4):1207-25. Review.
Lockhart AC, Braun RD, Yu D, Ross JR, Dewhirst MW, Klitzman B, Yuan F, Grichnik JM, Proia AD, Conway DA, Mann G, Hurwitz HI. A clinical model of dermal wound angiogenesis. Wound Repair Regen. 2003 Jul-Aug;11(4):306-13.
Lockhart AC, Braun RD, Yu D, Ross JR, Dewhirst MW, Humphrey JS, Thompson S, Williams KM, Klitzman B, Yuan F, Grichnik JM, Proia AD, Conway DA, Hurwitz HI. Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor. Clin Cancer Res. 2003 Feb;9(2):586-93.
Hurwitz, H., S.N. Holden, and S.G. Eckhardt, Clinical evaluation of ZD6474, an orally active inhibitor of VEGF signaling in patients with solid tumors. Proceedings of the American Society of Clinical Oncology, 2002. 21: p. Abstract 325.
Chang HY, Sneddon JB, Alizadeh AA, Sood R, West RB, Montgomery K, Chi JT, van de Rijn M, Botstein D, Brown PO. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol. 2004 Feb;2(2):E7. Epub 2004 Jan 13.
Hurwitz, H., et al. Wound healing/bleeding in metastatic colorectal cancer patients who undergo surgery during treatment with bevacizumab. in Proc Am Soc Clin Oncol. 2004.
Scappaticci, F., et al. Analysis of wound healing and bleeding post-surgery in metastatic colorectal cancer patients treated with bevacizumab. in Proc Am Soc Clin Oncol. 2004.
Hurwitz, H., et al. Clinical evaluation of ZD6474, an orally active inhibitor of VEGF signaling, in patients with solid tumors. in Proc Am Soc Clin Oncol. 2002.
Gerber HP, Kowalski J, Sherman D, Eberhard DA, Ferrara N. Complete inhibition of rhabdomyosarcoma xenograft growth and neovascularization requires blockade of both tumor and host vascular endothelial growth factor. Cancer Res. 2000 Nov 15;60(22):6253-8.
Kim ES, Serur A, Huang J, Manley CA, McCrudden KW, Frischer JS, Soffer SZ, Ring L, New T, Zabski S, Rudge JS, Holash J, Yancopoulos GD, Kandel JJ, Yamashiro DJ. Potent VEGF blockade causes regression of coopted vessels in a model of neuroblastoma. Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11399-404. Epub 2002 Aug 12.
Brookmeyer, R. and J.J. Crowley, A confidence interval for the median survival time. Biometrics, 1982. 38: p. 29-41.

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00447330     History of Changes
Other Study ID Numbers: Pro00008710
11100 ( Other Identifier: Old FDA IND Number )
8797 ( Other Identifier: Duke legacy protocol number )
First Submitted: March 13, 2007
First Posted: March 14, 2007
Results First Submitted: January 20, 2015
Results First Posted: January 28, 2015
Last Update Posted: February 13, 2015
Last Verified: July 2014

Keywords provided by Duke University:
metastatic esophagogastric adenocarcinomas

Additional relevant MeSH terms:
Neoplasm Metastasis
Stomach Neoplasms
Esophageal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplastic Processes
Pathologic Processes
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action

To Top