Chemotherapy Options for the First Line Chemotherapy in Elderly Patient With Advanced Gastric Cancer

Comparison of Efficacy and Tolerance Between Combination Therapy and Monotherapy as a First Line Chemotherapy in Elderly Patient With Advanced Gastric Cancer; Multicenter Randomized Phase 3 Study

The investigators compare the overall survival between combination chemotherapy and monochemotherapy as a first-line chemotherapy in elderly patients with metastatic or recurrent gastric cancer. The investigators also compare the progression free survival, response rate, safety, and, quality of life between two groups, and evaluate that the comprehensive geriatric assessment tested at baseline can predict the toxicity and compliance of treatment, survival of the patients.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Capecitabine/cisplatin; Drug: S-1/cisplatin; Drug: Capecitabine/oxaliplatin; Drug: 5-fluorouracil/oxaliplatin; Drug: Capecitabine; Drug: S-1; Drug: 5-fluorouracil

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Anyang, Korea, Republic of, 431-796
    • Hallym University Sacred Heart Hospital
  • Busan, Korea, Republic of
    • Inje University Haeundae Paik Hospital
  • Cheongju, Korea, Republic of, 361-711
    • Chungbuk National University Hospital
  • Daegu, Korea, Republic of, 702-210
    • Kyungpook National University Medical Center
  • Daegu, Korea, Republic of
    • Yeongnam University Medical Center
  • Goyang, Korea, Republic of, 410-769
    • National Cancer Center
  • Incheon, Korea, Republic of, 400-713
    • Gachon University Gil Medical Center
  • Pusan, Korea, Republic of, 614-735
    • Inje University Pusan Paik Hospital
  • Seongnam, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 156-707
    • SMG-SNU Boramae Medical Center
  • Seoul, Korea, Republic of
    • Kangbuk Samsung Hospital
  • Seoul, Korea, Republic of
    • Inje University Sanggye Paik Hospital
  • Uijeongbu, Korea, Republic of
    • The Catholic University of Korea Uijeongbu St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• .Metastatic or recurrent, histologically confirmed adenocarcinoma of stomach - Previously untreated patients, including patients with previous adjuvant chemotherapy completed more than 6 months
• 70 yrs or older
• Eastern Cooperative Oncology Group 0-2
• Measurable or evaluable disease

• Adequate major organ functions

  • Hb ≥ 9.0 g/dL
  • White blood cell count ≥ 3000/μL
  • Absolute Neutrophil Count (ANC) ≥ 1500/μL [*ANC = neutrophil segs ＋ neutrophil bands]
  • Platelet ≥ 100 × 103/ μL
  • Total bilirubin ≤ 1.5 ×UNL, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3.0x UNL(in case of liver metastasis, AST/ALT ≤ 5.0 x UNL)
  • Serum creatinine ≤ 1.5 × UNL (in case of serum creatinine > 1.5 mg/dL , Ccr should be >= 50 mL/min, Ccr is calculated by Cockcroft-Gault or 24hr urine collection)
• Life expectancy > 3month
• Written informed consent

Exclusion Criteria:

• Metastatic or recurrent stomach cancer other than adenocarcinoma
• HER-2 positive
• Clinically significant, uncontrolled gastric outlet obstruction, bleeding, or perforation
• Radiation therapy within the previous 2wks
• Major surgery or trauma within the previous 4wks
• Other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix)
• Uncontrolled brain metastasis
• Presence of other serious disease (cardiovascular, hepatic, infection etc.)
• Patients who participated in other clinical trials within the previous 30days
• Men of childbearing potential not willing to use effective means of contraception

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Platinum/fluoropyrimidine combination chemotherapy	Drug: Capecitabine/cisplatin; Capecitabine/cisplatin (XP) : cisplatin 50mg/m2 (80% dose of 60mg/2m) iv over 15min D1, capecitabine 1000mg/m2 (80% dose of 1250mg/m2) po bid D1-14, q 3wks; Drug: S-1/cisplatin; S-1/cisplatin (SP) : cisplatin 50mg/m2 (80% dose of 60mg/2m) iv ov 15min D1, S-1 30mg/m2 (80% dose of 40mg/m2) po bid D1-14, q3wks; Drug: Capecitabine/oxaliplatin; Capecitabine+oxaliplatin (XELOX): oxaliplatin 100mg/m2 (80% dose of 130mg/m2)iv ov 120min D1, capecitabine 800mg/m2 (80% dose of 1000mg/m2) po bid D1-14, q3wks; Drug: 5-fluorouracil/oxaliplatin; 5-fluorouracil/oxaliplatin (FOLFOX): oxaliplatin 80mg/m2 (80% dose of 100mg/m2) iv ov 120min, leucovorin 80mg/m2 (80% dose of 100mg/m2) iv ov 120min, 5-fluorouracil 1900mg/m2 (80% dose of 2400mg/m2) iv ov 46h D1, q 2wks
Active Comparator: Fluoropyrimidine monochemotherapy	Drug: Capecitabine; Capecitabine : 1250mg/m2 po bid D1-14 q3wks (if Ccr <60ml/min, 1000mg/m2 po bid); Drug: S-1; S-1 : 40mg/m2 po bid D1-14 q3wks (if Ccr <60ml/min, 30mg/m2 po bid); Drug: 5-fluorouracil; 5-fluorouracil (FL) : leucovorin 100mg/m2 iv ov 2h, 5-fluorouracil 2400mg/m2 iv ov 46h D1, q2wks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
comparison of overall survival	upto 3years

Secondary Outcome Measures

Outcome Measure	Time Frame
comparison of progression-free survival	upto 2years
comparison of response rate	upto 2years
comparison of adverse events	upto 2yrs
comparison of quality of life	upto 2years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
comprehensive geriatric assessment	The investigators are going to evaluate that comprehensive geriatric assessment tested at baseline can predict the toxicity and compliance to treatment, survival of patients. Comprehensive geriatric assessment will not necessarily be tested in all subjects, but instead, screening tool (KG-7 (Korean screening tool for the elderly)) will be tested in all subjects.	baseline

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Korean Cancer Study Group; Ministry of Health & Welfare, Korea
• Investigators: Principal Investigator: IN SIL CHOI, M.D., Ph.D., SMG-SNU Boramae Medical Center

Publications and helpful links

General Publications

• Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. doi: 10.1056/NEJMoa073149.
• Lee JL, Kang YK, Kang HJ, Lee KH, Zang DY, Ryoo BY, Kim JG, Park SR, Kang WK, Shin DB, Ryu MH, Chang HM, Kim TW, Baek JH, Min YJ. A randomised multicentre phase II trial of capecitabine vs S-1 as first-line treatment in elderly patients with metastatic or recurrent unresectable gastric cancer. Br J Cancer. 2008 Aug 19;99(4):584-90. doi: 10.1038/sj.bjc.6604536. Epub 2008 Jul 29.
• Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. doi: 10.1093/annonc/mdn717. Epub 2009 Jan 19.
• Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. doi: 10.1016/S1470-2045(08)70035-4. Epub 2008 Feb 20.
• Koizumi W, Kurihara M, Nakano S, Hasegawa K. Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. For the S-1 Cooperative Gastric Cancer Study Group. Oncology. 2000 Apr;58(3):191-7. doi: 10.1159/000012099.
• Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. doi: 10.1200/JCO.2003.04.130.
• Kim NK, Park YS, Heo DS, Suh C, Kim SY, Park KC, Kang YK, Shin DB, Kim HT, Kim HJ, et al. A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer. Cancer. 1993 Jun 15;71(12):3813-8. doi: 10.1002/1097-0142(19930615)71:123.0.co;2-5.
• Vanhoefer U, Rougier P, Wilke H, Ducreux MP, Lacave AJ, Van Cutsem E, Planker M, Santos JG, Piedbois P, Paillot B, Bodenstein H, Schmoll HJ, Bleiberg H, Nordlinger B, Couvreur ML, Baron B, Wils JA. Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol. 2000 Jul;18(14):2648-57. doi: 10.1200/JCO.2000.18.14.2648.
• Lacave AJ, Baron FJ, Anton LM, Estrada E, De Sande LM, Palacio I, Esteban E, Gracia JM, Buesa JM, Fernandez OA, et al. Combination chemotherapy with cisplatin and 5-fluorouracil 5-day infusion in the therapy of advanced gastric cancer: a phase II trial. Ann Oncol. 1991 Nov-Dec;2(10):751-4. doi: 10.1093/oxfordjournals.annonc.a057858.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): February 1, 2020
• Study Completion (Actual): February 1, 2020

Study Registration Dates

• First Submitted: April 9, 2014
• First Submitted That Met QC Criteria: April 14, 2014
• First Posted (Estimate): April 15, 2014

Study Record Updates

• Last Update Posted (Actual): October 23, 2020
• Last Update Submitted That Met QC Criteria: October 22, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: gastric cancer, elderly, chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cisplatin; Fluorouracil; Capecitabine; Oxaliplatin
• Other Study ID Numbers: 20140113/16-2014-9/021