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

Sponsor
National Cancer Centre, Singapore (Other)
Overall Status
Terminated
CT.gov ID
NCT02720926
Collaborator
Novartis (Industry)
3
Enrollment
1
Location
1
Arm
4
Duration (Months)
0.7
Patients Per Site Per Month

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
Actual Enrollment :
3 participants
Allocation:
N/A
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 :
Sep 1, 2011
Actual Primary Completion Date :
Jan 1, 2012
Actual Study Completion Date :
Jan 1, 2012

Arms and Interventions

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 Names:
  • 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;

    Outcome Measures

    Primary Outcome Measures

    1. Determine the recommended phase 2 dose of TKI258 in combination with XELOX (Capecitabine and Oxaliplatin) [42 days]

    Secondary Outcome Measures

    1. Describe the toxic effects of TKI258 when administered in combination with XELOX chemotherapy. [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 [42 days]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    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.

    1. 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.

    2. Baseline left ventricular ejection fraction (LVEF) >= 50%

    3. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National Cancer Centre singapore Singapore Singapore

    Sponsors and Collaborators

    • National Cancer Centre, Singapore
    • Novartis

    Investigators

    • Principal Investigator: Iain BH Tan, Dr, National Cancer Centre, Singapore

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Centre, Singapore
    ClinicalTrials.gov Identifier:
    NCT02720926
    Other Study ID Numbers:
    • NCC 10-03
    First Posted:
    Mar 28, 2016
    Last Update Posted:
    Mar 28, 2016
    Last Verified:
    Mar 1, 2016
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:
    Stomach Neoplasms
    Capecitabine
    Oxaliplatin

    Study Results

    No Results Posted as of Mar 28, 2016