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.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
capecitabine (Xeloda), oxaliplatin and bevacizumab (Avastin)
Drug
—
UNRESOLVED
Design
Arms and outcomes
Arms (1)
type
EXPERIMENTAL
label
1
interventionNames
Drug: capecitabine (Xeloda), oxaliplatin and bevacizumab (Avastin)
Primary outcomes (1)
measure
Median Progression-Free Survival (PFS)
timeFrame
5 years from study start date
description
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 outcomes (3)
measure
To Assess the Safety and Tolerability of the Combination of Bevacizumab, Oxaliplatin and Capecitabine in Patients With Previously Untreated Metastatic Esophagogastric Adenocarcinoma
Eligibility
Eligibility (as posted)
Sex
All
Minimum age
18 Years
Show eligibility criteria text
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
References
Publications (41)
BACKGROUNDJemal 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. doi: 10.3322/canjclin.55.1.10. PMID 15661684
BACKGROUNDBollschweiler E, Wolfgarten E, Gutschow C, Holscher AH. Demographic variations in the rising incidence of esophageal adenocarcinoma in white males. Cancer. 2001 Aug 1;92(3):549-55. doi: 10.1002/1097-0142(20010801)92:33.0.co;2-l. PMID 11505399
BACKGROUNDWijnhoven 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. doi: 10.1046/j.1365-2168.1999.01082.x. PMID 10215831
BACKGROUNDGlimelius B, Ekstrom K, Hoffman K, Graf W, Sjoden PO, Haglund U, Svensson C, Enander LK, Linne T, Sellstrom 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. doi: 10.1023/a:1008243606668. PMID 9093725
BACKGROUNDHsu 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. doi: 10.1159/000227702. PMID 9216850
BACKGROUNDLeichman 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. doi: 10.1002/1097-0142(19840101)53:13.0.co;2-j. PMID 6317158
BACKGROUNDWebb 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. doi: 10.1200/JCO.1997.15.1.261.
timeFrame
Every 21 days
description
Number of subjects who experienced an adverse event
measure
Response Rate
timeFrame
Every 9 weeks for up to 1 year
description
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.
measure
Median Survival
timeFrame
5 years after study start date
description
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.
BACKGROUNDMiwa 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. doi: 10.1016/s0959-8049(98)00058-6. PMID 9849491
BACKGROUNDSchuller 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. doi: 10.1007/s002800050043. PMID 10755317
BACKGROUNDHong 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. doi: 10.1093/annonc/mdh343. PMID 15319239
BACKGROUNDKoizumi 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. doi: 10.1159/000069313. PMID 12697963
BACKGROUNDKim 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. doi: 10.1093/annonc/mdf323. PMID 12453857
BACKGROUNDEvans 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. doi: 10.1093/annonc/mdf243. PMID 12196374
BACKGROUNDAl-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. doi: 10.1200/JCO.2004.07.042. PMID 14966088
BACKGROUNDLouvet C, Andre T, Tigaud JM, Gamelin E, Douillard JY, Brunet R, Francois 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. doi: 10.1200/JCO.2002.02.021. PMID 12454110
BACKGROUNDDiaz-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. doi: 10.1093/annonc/mdf065. PMID 12056706
BACKGROUNDCassidy J, Tabernero J, Twelves C, Brunet R, Butts C, Conroy T, Debraud F, Figer A, Grossmann J, Sawada N, Schoffski P, Sobrero A, Van Cutsem E, Diaz-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. doi: 10.1200/JCO.2004.11.069. PMID 15169795
BACKGROUNDShields 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. doi: 10.1002/cncr.11925. PMID 14745869
BACKGROUNDde 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. doi: 10.1200/JCO.2000.18.16.2938. PMID 10944126
BACKGROUNDSumpter, K., et al. Randomised, mulitcenter phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer: confirmation of dose escalation. in Proc Am Soc Clin Onocol. 2003.
BACKGROUNDChong 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. doi: 10.1016/j.clon.2004.12.004. No abstract available. PMID 15830568
BACKGROUNDHurwitz 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. doi: 10.1056/NEJMoa032691. PMID 15175435
BACKGROUNDGiantonio, 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.
BACKGROUNDMiller, 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.
BACKGROUNDShah, 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.
BACKGROUNDGoldberg, 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.
BACKGROUNDTakimoto 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. doi: 10.1200/JCO.2003.11.015. PMID 12860942
BACKGROUNDXeloda Investigator Drug Brochure (Ro 09-1978), in Version 6. January 2002.
BACKGROUNDIshitsuka, 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.
BACKGROUNDGiantonio, 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.
BACKGROUNDHochster, 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.
BACKGROUNDPoon RT, Fan ST, Wong J. Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol. 2001 Feb 15;19(4):1207-25. doi: 10.1200/JCO.2001.19.4.1207. PMID 11181687
BACKGROUNDLockhart 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. doi: 10.1046/j.1524-475x.2003.11411.x. PMID 12846919
BACKGROUNDLockhart 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. PMID 12576422
BACKGROUNDHolden SN, Eckhardt SG, Basser R, de Boer R, Rischin D, Green M, Rosenthal MA, Wheeler C, Barge A, Hurwitz HI. Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors. Ann Oncol. 2005 Aug;16(8):1391-7. doi: 10.1093/annonc/mdi247. Epub 2005 May 19. PMID 15905307
BACKGROUNDChang 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. doi: 10.1371/journal.pbio.0020007. Epub 2004 Jan 13. PMID 14737219
BACKGROUNDHurwitz, 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.
BACKGROUNDScappaticci, 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.
BACKGROUNDGerber 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. PMID 11103779
BACKGROUNDKim 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. doi: 10.1073/pnas.172398399. Epub 2002 Aug 12. PMID 12177446
BACKGROUNDBrookmeyer, R. and J.J. Crowley, A confidence interval for the median survival time. Biometrics, 1982. 38: p. 29-41.