TS-1 in Combination With Calcium Folinate in Patients With Heavily Pre-treated mCRC

NCT03517618 | Completed Phase 2

• 1 other identifier: TG1307
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To determine disease control rate (DCR) of TS-1® in patients with heavily pre-treated metastatic colorectal cancer Secondary Objectives:

• To determine objective response rate (ORR)
• To determine time to progression (TTP)
• To determine overall survival (OS)
• To assess incidence of adverse events (AEs), serious adverse events (SAEs) \[Safety and Tolerability\]

Conditions

Metastatic Colorectal Cancer

Keywords

A phase II study; Heavily pre-treated metastatic colorectal cancer; S-1; oral leucovrin

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate (DCR)

  Documented objective response (OR) (defined as partial response \[PR\] or complete response \[CR\]), assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at any time during trial participation by Investigator assessment

  6 months(an expected average)

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  6 months(an expected average)

• Time to Progression (TTP)

  until disease progression, intolerable toxicity, 12 months(an expected average)

• Overall survival (OS)

  at death or at the end of study, 24 months(an expected average)

• Incidence of adverse events (AEs), serious adverse events (SAEs) [Safety and Tolerability]

  From the date of study entry until 30 days after the last dose of study treatment

Study Arms (1)

S-1 + leucovorin

EXPERIMENTAL

Single arm

Drug: S-1+leucovorin

Interventions

S-1+leucovorin DRUG

Eligible patients will receive TS-1 orally 40-60 mg (depending on patient's body surface area (BSA)) in combination with calcium folinate 30 mg twice a day for 7 days in a 2-week cycle. The treatment will be administered until disease progression, intolerable toxicity, or consent withdrawal during any time of the study.

Also known as: TS-1+calcium folinate

S-1 + leucovorin

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• histologically or cytologically confirmed colorectal adenocarcinoma;
• metastatic and unresectable disease;
• presence of at least one measurable tumor lesion which is defined as lesion that can be measured in at least one dimension (longest diameter) with a minimum size of:
• mm by CT scan and MRI (no less than double the slice thickness and a minimum of 10mm);
• mm by conventional techniques;
• previously treatment to
• fluoropyrimidine, oxaliplatin and irinotecan;
• at least one targeted therapy
• adequate hematopoietic function which is defined as below:
• hemoglobin ≥ 9 g/dL;
• absolute neutrophil count (ANC) ≥ 1,500/mm3;
• platelet count ≥ 100,000/mm3;
• adequate hepatic function which is defined as below:
• total bilirubin ≤ 2 times upper limit of normal (ULN);
• hepatic transaminases (ALT and AST) ≤ 3 x ULN. If there are known liver metastases, ALT or AST must be ≤ 5 x ULN;

You may not qualify if:

• history or known presence of brain metastasis;
• presence of mental disease or psychotic manifestation;
• significant medical conditions that is contraindicated to study medication or render patient at high risk from treatment complications based on investigator's discretion;
• presence of diarrhea ≥ grade 2 in common terminology criteria for adverse event version 4.0 (CTCAE v4.0);
• other malignancy within the past 5 years (different site or histology) except for adequately treated basal or squamous cell skin cancer or cervical cancer in situ;
• recent (within 30 days prior to study treatment) treatment of another investigational drug;
• pregnant women or nursing mothers, or positive pregnancy test for women of childbearing potential. Patients with childbearing potential should have effective contraception for both the patient and his or her partner during the study.

Sponsors & Collaborators

• TTY Biopharm: lead
• Chang Gung Memorial Hospital: collaborator

Study Sites (1)

Chang-Gung Memorial Hospital, Linkou

Linkou District, Taiwan

Location

Related Publications (30)

• Lee WS, Yun SH, Chun HK, Lee WY, Yun HR, Kim J, Kim K, Shim YM. Pulmonary resection for metastases from colorectal cancer: prognostic factors and survival. Int J Colorectal Dis. 2007 Jun;22(6):699-704. doi: 10.1007/s00384-006-0218-2. Epub 2006 Nov 16.

  PMID: 17109105 BACKGROUND

• Van Cutsem E, Nordlinger B, Adam R, Kohne CH, Pozzo C, Poston G, Ychou M, Rougier P; European Colorectal Metastases Treatment Group. Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. Eur J Cancer. 2006 Sep;42(14):2212-21. doi: 10.1016/j.ejca.2006.04.012. Epub 2006 Aug 10.

  PMID: 16904315 BACKGROUND

• Yoo PS, Lopez-Soler RI, Longo WE, Cha CH. Liver resection for metastatic colorectal cancer in the age of neoadjuvant chemotherapy and bevacizumab. Clin Colorectal Cancer. 2006 Sep;6(3):202-7. doi: 10.3816/CCC.2006.n.036.

  PMID: 17026789 BACKGROUND

• Alberts SR, Horvath WL, Sternfeld WC, Goldberg RM, Mahoney MR, Dakhil SR, Levitt R, Rowland K, Nair S, Sargent DJ, Donohue JH. Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: a North Central Cancer Treatment Group phase II study. J Clin Oncol. 2005 Dec 20;23(36):9243-9. doi: 10.1200/JCO.2005.07.740. Epub 2005 Oct 17.

  PMID: 16230673 BACKGROUND

• Dawood O, Mahadevan A, Goodman KA. Stereotactic body radiation therapy for liver metastases. Eur J Cancer. 2009 Nov;45(17):2947-59. doi: 10.1016/j.ejca.2009.08.011. Epub 2009 Sep 19.

  PMID: 19773153 BACKGROUND

• Kemeny N. Management of liver metastases from colorectal cancer. Oncology (Williston Park). 2006 Sep;20(10):1161-76, 1179; discussion 1179-80, 1185-6.

  PMID: 17024869 BACKGROUND

• Muratore A, Zorzi D, Bouzari H, Amisano M, Massucco P, Sperti E, Capussotti L. Asymptomatic colorectal cancer with un-resectable liver metastases: immediate colorectal resection or up-front systemic chemotherapy? Ann Surg Oncol. 2007 Feb;14(2):766-70. doi: 10.1245/s10434-006-9146-1. Epub 2006 Nov 14.

  PMID: 17103261 BACKGROUND

• Andre T, Louvet C, Maindrault-Goebel F, Couteau C, Mabro M, Lotz JP, Gilles-Amar V, Krulik M, Carola E, Izrael V, de Gramont A. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR. Eur J Cancer. 1999 Sep;35(9):1343-7. doi: 10.1016/s0959-8049(99)00150-1.

  PMID: 10658525 BACKGROUND

• Jager E, Heike M, Bernhard H, Klein O, Bernhard G, Lautz D, Michaelis J, Meyer zum Buschenfelde KH, Knuth A. Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: results of a randomized multicenter trial. Study Group for Palliative Treatment of Metastatic Colorectal Cancer Study Protocol 1. J Clin Oncol. 1996 Aug;14(8):2274-9. doi: 10.1200/JCO.1996.14.8.2274.

  PMID: 8708717 BACKGROUND

• Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crino L, Benedetti G, Evangelista W, Fanchini L, Cortesi E, Picone V, Vitello S, Chiara S, Granetto C, Porcile G, Fioretto L, Orlandini C, Andreuccetti M, Masi G; Gruppo Oncologico Nord Ovest. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007 May 1;25(13):1670-6. doi: 10.1200/JCO.2006.09.0928.

  PMID: 17470860 BACKGROUND

• Souglakos J, Androulakis N, Syrigos K, Polyzos A, Ziras N, Athanasiadis A, Kakolyris S, Tsousis S, Kouroussis Ch, Vamvakas L, Kalykaki A, Samonis G, Mavroudis D, Georgoulias V. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer. 2006 Mar 27;94(6):798-805. doi: 10.1038/sj.bjc.6603011.

  PMID: 16508637 BACKGROUND

• Cassidy J, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Saltz L. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008 Apr 20;26(12):2006-12. doi: 10.1200/JCO.2007.14.9898.

  PMID: 18421053 BACKGROUND

• Petrelli N, Herrera L, Rustum Y, Burke P, Creaven P, Stulc J, Emrich LJ, Mittelman A. A prospective randomized trial of 5-fluorouracil versus 5-fluorouracil and high-dose leucovorin versus 5-fluorouracil and methotrexate in previously untreated patients with advanced colorectal carcinoma. J Clin Oncol. 1987 Oct;5(10):1559-65. doi: 10.1200/JCO.1987.5.10.1559.

  PMID: 2443619 BACKGROUND

• Wolmark N, Rockette H, Fisher B, Wickerham DL, Redmond C, Fisher ER, Jones J, Mamounas EP, Ore L, Petrelli NJ, et al. The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03. J Clin Oncol. 1993 Oct;11(10):1879-87. doi: 10.1200/JCO.1993.11.10.1879.

  PMID: 8410113 BACKGROUND

• Cassidy 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 BACKGROUND

• Porschen R, Arkenau HT, Kubicka S, Greil R, Seufferlein T, Freier W, Kretzschmar A, Graeven U, Grothey A, Hinke A, Schmiegel W, Schmoll HJ; AIO Colorectal Study Group. Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J Clin Oncol. 2007 Sep 20;25(27):4217-23. doi: 10.1200/JCO.2006.09.2684. Epub 2007 Jun 4.

  PMID: 17548840 BACKGROUND

• Sargent DJ, Kohne CH, Sanoff HK, Bot BM, Seymour MT, de Gramont A, Porschen R, Saltz LB, Rougier P, Tournigand C, Douillard JY, Stephens RJ, Grothey A, Goldberg RM. Pooled safety and efficacy analysis examining the effect of performance status on outcomes in nine first-line treatment trials using individual data from patients with metastatic colorectal cancer. J Clin Oncol. 2009 Apr 20;27(12):1948-55. doi: 10.1200/JCO.2008.20.2879. Epub 2009 Mar 2.

  PMID: 19255311 BACKGROUND

• Chibaudel B, Tournigand C, Andre T, de Gramont A. Therapeutic strategy in unresectable metastatic colorectal cancer. Ther Adv Med Oncol. 2012 Mar;4(2):75-89. doi: 10.1177/1758834011431592.

  PMID: 22423266 BACKGROUND

• Lievre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, Ychou M, Bouche O, Landi B, Louvet C, Andre T, Bibeau F, Diebold MD, Rougier P, Ducreux M, Tomasic G, Emile JF, Penault-Llorca F, Laurent-Puig P. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008 Jan 20;26(3):374-9. doi: 10.1200/JCO.2007.12.5906.

  PMID: 18202412 BACKGROUND

• Grothey A, Sargent D, Goldberg RM, Schmoll HJ. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol. 2004 Apr 1;22(7):1209-14. doi: 10.1200/JCO.2004.11.037.

  PMID: 15051767 BACKGROUND

• Ohtsu A, Baba H, Sakata Y, Mitachi Y, Horikoshi N, Sugimachi K, Taguchi T. Phase II study of S-1, a novel oral fluorophyrimidine derivative, in patients with metastatic colorectal carcinoma. S-1 Cooperative Colorectal Carcinoma Study Group. Br J Cancer. 2000 Jul;83(2):141-5. doi: 10.1054/bjoc.2000.1236.

  PMID: 10901361 BACKGROUND

• Shirao K, Ohtsu A, Takada H, Mitachi Y, Hirakawa K, Horikoshi N, Okamura T, Hirata K, Saitoh S, Isomoto H, Satoh A. Phase II study of oral S-1 for treatment of metastatic colorectal carcinoma. Cancer. 2004 Jun 1;100(11):2355-61. doi: 10.1002/cncr.20277.

  PMID: 15160338 BACKGROUND

• Van den Brande J, Schoffski P, Schellens JH, Roth AD, Duffaud F, Weigang-Kohler K, Reinke F, Wanders J, de Boer RF, Vermorken JB, Fumoleau P. EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer. Br J Cancer. 2003 Mar 10;88(5):648-53. doi: 10.1038/sj.bjc.6600781.

  PMID: 12659110 BACKGROUND

• Jeung HC, Rha SY, Cho BC, Yoo NC, Roh JK, Roh WJ, Chung HC, Ahn JB. A phase II trial of S-1 monotherapy in metastatic colorectal cancer after failure of irinotecan- and oxaliplatin-containing regimens. Br J Cancer. 2006 Dec 18;95(12):1637-41. doi: 10.1038/sj.bjc.6603468. Epub 2006 Nov 14.

  PMID: 17106441 BACKGROUND

• Lee DJ, Lee J, Lee HY, Lim T, Lee SJ, Yi SY, Park SH, Park JO, Lim HY, Kang WK, Park YS. Salvage S-1 monotherapy in metastatic colorectal cancer patients who failed irinotecan-based or oxaliplatin-based chemotherapy. Med Oncol. 2011 Dec;28 Suppl 1:S291-4. doi: 10.1007/s12032-010-9755-1. Epub 2010 Nov 30.

  PMID: 21116875 BACKGROUND

• Yamada Y, Tahara M, Miya T, Satoh T, Shirao K, Shimada Y, Ohtsu A, Sasaki Y, Tanigawara Y. Phase I/II study of oxaliplatin with oral S-1 as first-line therapy for patients with metastatic colorectal cancer. Br J Cancer. 2008 Mar 25;98(6):1034-8. doi: 10.1038/sj.bjc.6604271. Epub 2008 Mar 4.

  PMID: 18319719 BACKGROUND

• Kim SY, Hong YS, Kim BC, Park JW, Choi HS, Jeong SY, Kim DY, Hong CW, Sohn DK, Jung KH. A phase II study of S-1 plus irinotecan and oxaliplatin in heavily-treated patients with metastatic colorectal cancer. Invest New Drugs. 2009 Jun;27(3):269-74. doi: 10.1007/s10637-008-9177-5. Epub 2008 Sep 25.

  PMID: 18815728 BACKGROUND

• Muro K, Boku N, Shimada Y, Tsuji A, Sameshima S, Baba H, Satoh T, Denda T, Ina K, Nishina T, Yamaguchi K, Takiuchi H, Esaki T, Tokunaga S, Kuwano H, Komatsu Y, Watanabe M, Hyodo I, Morita S, Sugihara K. Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study). Lancet Oncol. 2010 Sep;11(9):853-60. doi: 10.1016/S1470-2045(10)70181-9. Epub 2010 Aug 12.

  PMID: 20708966 BACKGROUND

• Hong YS, Park YS, Lim HY, Lee J, Kim TW, Kim KP, Kim SY, Baek JY, Kim JH, Lee KW, Chung IJ, Cho SH, Lee KH, Shin SJ, Kang HJ, Shin DB, Jo SJ, Lee JW. S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for first-line treatment of patients with metastatic colorectal cancer: a randomised, non-inferiority phase 3 trial. Lancet Oncol. 2012 Nov;13(11):1125-32. doi: 10.1016/S1470-2045(12)70363-7. Epub 2012 Oct 10.

  PMID: 23062232 BACKGROUND

• Koizumi W, Boku N, Yamaguchi K, Miyata Y, Sawaki A, Kato T, Toh Y, Hyodo I, Nishina T, Furuhata T, Miyashita K, Okada Y. Phase II study of S-1 plus leucovorin in patients with metastatic colorectal cancer. Ann Oncol. 2010 Apr;21(4):766-771. doi: 10.1093/annonc/mdp371. Epub 2009 Oct 14.

  PMID: 19828562 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Hung-Chih Hsu

  Chang Gung Memorial Hospital, Linkou, Taiwan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2018
• First Posted: May 7, 2018
• Study Start: July 5, 2014
• Primary Completion: June 18, 2015
• Study Completion: June 18, 2015
• Last Updated: May 7, 2018

Record last verified: 2018-04

Locations

TW (1)