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Study of TKI 258 in Combination With Xeloda and Oxaliplatin in Advanced Colorectal and Gastric Cancer

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. Identifier: NCT02720926
Recruitment Status : Terminated (Unafavourable toxicity profile)
First Posted : March 28, 2016
Last Update Posted : March 28, 2016
Information provided by (Responsible Party):
National Cancer Centre, Singapore

Brief Summary:
Standard "3+3" dose escalation design of TKI258/XELOX in advanced gastric/gastro-oesophageal and colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Gastric Cancer Drug: Xeloda, Drug: Oxaliplatin Drug: TKI258 Phase 1

Detailed Description:
This is a "3+3" dose escalation design with 4 pre-defined TKI258 dose levels (200mg, 300mg, 400mg and 500mg daily with 5 days on and 2 days off schedule) in combination with a fixed standard dose of XELOX (Capecitabine and Oxaliplatin) to establish the recommended phase 2 dose.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of TKI 258 in Combination With Xeloda and Oxaliplatin in Upfront Treatment of Advanced Colorectal and Gastric Cancer With a Dose Expansion Cohort in Advanced Gastric Cancer
Study Start Date : September 2011
Actual Primary Completion Date : January 2012
Actual Study Completion Date : January 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer

Arm Intervention/treatment
Experimental: TKI258 combined with Xeloda/Oxaliplatin
TKI258 200 mg once a day (OD) 5 days on/2 days off Capecitabine (Xeloda) 2000 mg/m2 bid d1-14 Oxaliplatin 130mg/m2 d1 q21days
Drug: Xeloda,
Capecitabine (xeloda): 2000mg/m2, twice a day on Day 1-14;
Other Name: capecitabine

Drug: Oxaliplatin
Oxaliplatin: 130mg/m2 day 1 every 21days

Drug: TKI258
4 dose levels of TKI258: 200mg, 300mg, 400mg, 500mg once daily, 5days on and 2 days off;

Primary Outcome Measures :
  1. Determine the recommended phase 2 dose of TKI258 in combination with XELOX (Capecitabine and Oxaliplatin) [ Time Frame: 42 days ]

Secondary Outcome Measures :
  1. Describe the toxic effects of TKI258 when administered in combination with XELOX chemotherapy. [ Time Frame: one year ]
    Toxicity will be graded using CTCAE version 4.0

  2. Measure the Area under the plasma concentration versus time curve (AUC) of TKI258 at specific timepoints [ Time Frame: 42 days ]

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.

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

Inclusion Criteria:

  1. Patients must have histologically confirmed gastric, gastro-oesophageal or colorectal adenocarcinoma.
  2. The gastric or gastro-oesophageal cancer must be locally advanced unresectable or metastatic. Colorectal cancer must be metastatic and for which subsequent resection of all metastatic disease is assessed not to be feasible.
  3. Age >18 years.
  4. Eastern Cooperative Oncology Group (ECOG) performance status <2 (Karnofsky >60%, see Appendix A).
  5. Life expectancy of greater than 3 months
  6. Patients must have normal organ and marrow function as defined below:

    • leukocytes >3,000/mcL
    • absolute neutrophil count >1,500/microliter (mcL) TKI258/XELOX phase 1 protocol version 3.3 Dated 30 November 2011 1 3
    • platelets >100,000/mcL
    • total bilirubin <= 1.5 x upper limit of normal (ULN)
    • aspartate aminotransferase (AST)/alanine aminotransferase (ALT) <2.5 X institutional upper limit of normal
    • creatinine within normal institutional limits OR
    • creatinine clearance >55 mL/min for patients with creatinine levels above institutional normal.
  7. The effects of TKI258 and XELOX on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  8. Baseline left ventricular ejection fraction (LVEF) >= 50%
  9. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Patients are not considered to have a "currently active" malignancy if they have TKI258/XELOX phase 1 protocol version 3.3 Dated 30 November 2011 1 4 completed therapy and are considered to have a less than 30% risk of relapse.
  2. Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TKI258 or XELOX, breastfeeding should be discontinued if the mother is treated with TKI258 or XELOX.
  3. Patients with prior history of transient ischemia attack or cerebrovascular disease or prior history of ischemia heart disease or myocardia infarction and 2 or more risk factors: ever smoker with > 30 packs per year exposure or on medication for diabetes mellitus or hypertension or hyperlipidemia.
  4. In addition for the Beginning at dose expansion cohort, the following exclusion criteria apply:

    • Patients who are not agreeable for collection of tumor tissue for correlative studies
    • Patients from whom tumor tissue for correlative studies cannot be safely obtained.

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 identifier (NCT number): NCT02720926

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National Cancer Centre singapore
Singapore, Singapore
Sponsors and Collaborators
National Cancer Centre, Singapore
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Principal Investigator: Iain BH Tan, Dr National Cancer Centre, Singapore

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Responsible Party: National Cancer Centre, Singapore Identifier: NCT02720926    
Other Study ID Numbers: NCC 10-03
First Posted: March 28, 2016    Key Record Dates
Last Update Posted: March 28, 2016
Last Verified: March 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents